Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

Science.gov (United States)

de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

2017-07-01

Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (ptest, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Letícia Flohr

2012-01-01

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

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

Science.gov (United States)

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

2014-06-01

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

Dose-volume analysis of predictors for chronic rectal toxicity after treatment of prostate cancer with adaptive image-guided radiotherapy

International Nuclear Information System (INIS)

Vargas, Carlos; Martinez, Alvaro; Kestin, Larry L.; Yan Di; Grills, Inga; Brabbins, Donald S.; Lockman, David M.; Liang Jian; Gustafson, Gary S.; Chen, Peter Y.; Vicini, Frank A.; Wong, John W.

2005-01-01

Purpose We analyzed our experience treating localized prostate cancer with image-guided off-line correction with adaptive high-dose radiotherapy (ART) in our Phase II dose escalation study to identify factors predictive of chronic rectal toxicity. Materials and Methods From 1999-2002, 331 patients with clinical stage T1-T3N0M0 prostate cancer were prospectively treated in our Phase II 3D conformal dose escalation ART study to a median dose of 75.6 Gy (range, 63.0-79.2 Gy), minimum dose to confidence limited-planning target volume (cl-PTV) in 1.8 Gy fractions (median isocenter dose = 79.7 Gy). Seventy-four patients (22%) also received neoadjuvant/adjuvant androgen deprivation therapy. A patient-specific cl-PTV was constructed using 5 computed tomography scans and 4 sets of electronic portal images by applying an adaptive process to assure target accuracy and minimize PTV margin. For each case, the rectum (rectal solid) was contoured from the sacroiliac joints or rectosigmoid junction (whichever was higher) to the anal verge or ischial tuberosities (whichever was lower), with a median volume of 81.2 cc. The rectal wall was defined using the rectal solid with an individualized 3-mm wall thickness (median volume = 29.8 cc). Rectal wall dose-volume histogram was used to determine the prescribed dose. Toxicity was quantified using the National Cancer Institute Common Toxicity Criteria 2.0. Multiple dose-volume endpoints were evaluated for their association with chronic rectal toxicity. Results Median follow-up was 1.6 years. Thirty-four patients (crude rate 10.3%) experienced Grade 2 chronic rectal toxicity at a median interval of 1.1 years. Nine patients (crude rate = 2.7%) experienced Grade ≥3 chronic rectal toxicity (1 was Grade 4) at a median interval of 1.2 years. The 3-year rates of Grade ≥2 and Grade ≥3 chronic rectal toxicity were 20% and 4%, respectively. Acute toxicity predicted for chronic: Acute Grade 2-3 rectal toxicity (p 40% respectively. The volume

Chronic toxicity of nickel-spiked freshwater sediments: variation in toxicity among eight invertebrate taxa and eight sediments

Science.gov (United States)

Besser, John M.; Brumbaugh, William G.; Ingersoll, Christopher G.; Ivey, Chris D.; Kunz, James L.; Kemble, Nile E.; Schlekat, Christian E.; Garman, Emily R.

2013-01-01

This study evaluated the chronic toxicity of Ni-spiked freshwater sediments to benthic invertebrates. A 2-step spiking procedure (spiking and sediment dilution) and a 2-stage equilibration period (10 wk anaerobic and 1 wk aerobic) were used to spike 8 freshwater sediments with wide ranges of acid-volatile sulfide (AVS; 0.94–38 µmol/g) and total organic carbon (TOC; 0.42–10%). Chronic sediment toxicity tests were conducted with 8 invertebrates (Hyalella azteca, Gammarus pseudolimnaeus, Chironomus riparius, Chironomus dilutus, Hexagenia sp., Lumbriculus variegatus, Tubifex tubifex, and Lampsilis siliquoidea) in 2 spiked sediments. Nickel toxicity thresholds estimated from species-sensitivity distributions were 97 µg/g and 752 µg/g (total recoverable Ni; dry wt basis) for sediments with low and high concentrations of AVS and TOC, respectively. Sensitive species were tested with 6 additional sediments. The 20% effect concentrations (EC20s) for Hyalella and Gammarus, but not Hexagenia, were consistent with US Environmental Protection Agency benchmarks based on Ni in porewater and in simultaneously extracted metals (SEM) normalized to AVS and TOC. For Hexagenia, sediment EC20s increased at less than an equimolar basis with increased AVS, and toxicity occurred in several sediments with Ni concentrations in SEM less than AVS. The authors hypothesize that circulation of oxygenated water by Hexagenia led to oxidation of AVS in burrows, creating microenvironments with high Ni exposure. Despite these unexpected results, a strong relationship between Hexagenia EC20s and AVS could provide a basis for conservative site-specific sediment quality guidelines for Ni.

A re-evaluation of PETROTOX for predicting acute and chronic toxicity of petroleum substances.

Science.gov (United States)

Redman, Aaron D; Parkerton, Thomas F; Leon Paumen, Miriam; Butler, Josh D; Letinski, Daniel J; den Haan, Klass

2017-08-01

The PETROTOX model was developed to perform aquatic hazard assessment of petroleum substances based on substance composition. The model relies on the hydrocarbon block method, which is widely used for conducting petroleum substance risk assessments providing further justification for evaluating model performance. Previous work described this model and provided a preliminary calibration and validation using acute toxicity data for limited petroleum substance. The objective of the present study was to re-evaluate PETROTOX using expanded data covering both acute and chronic toxicity endpoints on invertebrates, algae, and fish for a wider range of petroleum substances. The results indicated that recalibration of 2 model parameters was required, namely, the algal critical target lipid body burden and the log octanol-water partition coefficient (K OW ) limit, used to account for reduced bioavailability of hydrophobic constituents. Acute predictions from the updated model were compared with observed toxicity data and found to generally be within a factor of 3 for algae and invertebrates but overestimated fish toxicity. Chronic predictions were generally within a factor of 5 of empirical data. Furthermore, PETROTOX predicted acute and chronic hazard classifications that were consistent or conservative in 93 and 84% of comparisons, respectively. The PETROTOX model is considered suitable for the purpose of characterizing petroleum substance hazard in substance classification and risk assessments. Environ Toxicol Chem 2017;36:2245-2252. © 2017 SETAC. © 2017 SETAC.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-09-15

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

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

Science.gov (United States)

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

2011-08-01

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

40 CFR 797.1950 - Mysid shrimp chronic toxicity test.

Science.gov (United States)

2010-07-01

... on the chronic toxicity of chemical substances and mixtures (“chemicals”) subject to environmental... with the test design into retention chambers within the test and the control chambers. Mysids in the... and experimental history. Mysids used for establishing laboratory cultures may be purchased...

Chronic Toxic Metal Exposure and Cardiovascular Disease: Mechanisms of Risk and Emerging Role of Chelation Therapy.

Science.gov (United States)

Aneni, Ehimen C; Escolar, Esteban; Lamas, Gervasio A

2016-12-01

Over the last few decades, there has been a growing body of epidemiologic evidence linking chronic toxic metal exposure to cardiovascular disease-related morbidity and mortality. The recent and unexpectedly positive findings from a randomized, double-blind, multicenter trial of metal chelation for the secondary prevention of atherosclerotic cardiovascular disease (Trial to Assess Chelation Therapy (TACT)) have focused the discussion on the role of chronic exposure to toxic metals in the development and propagation of cardiovascular disease and the role of toxic metal chelation therapy in the secondary prevention of cardiovascular disease. This review summarizes the most recent evidence linking chronic toxic metal exposure to cardiovascular disease and examines the findings of TACT.

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

Energy Technology Data Exchange (ETDEWEB)

Holland, J.M.

2001-01-16

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

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

Directory of Open Access Journals (Sweden)

Anna C. Almeida

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

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

International Nuclear Information System (INIS)

McDermott, Catherine; Allshire, Ashley; Pelt, Frank N.A.M. van; Heffron, James J.A.

2007-01-01

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 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)

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

Science.gov (United States)

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

2016-12-01

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

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

Directory of Open Access Journals (Sweden)

Surender Singh

2017-01-01

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

Acute and chronic toxicity of veterinary antibiotics to Daphnia magna

DEFF Research Database (Denmark)

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

2000-01-01

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

Acute and Sub-chronic (28-day) Oral Toxicity Studies of ...

African Journals Online (AJOL)

Erah

was to investigate the acute and sub-chronic toxicity of A. conyzoides leaves in Wistar rats. Methods: In the acute test, the ... associated with navel in children [4], and in the treatment of ... Ethical Committee for Teaching and. Research (ref no.

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

NARCIS (Netherlands)

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

2000-01-01

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

Regenerative toxicology: the role of stem cells in the development of chronic toxicities.

Science.gov (United States)

Canovas-Jorda, David; Louisse, Jochem; Pistollato, Francesca; Zagoura, Dimitra; Bremer, Susanne

2014-01-01

Human stem cell lines and their derivatives, as alternatives to the use of animal cells or cancer cell lines, have been widely discussed as cellular models in predictive toxicology. However, the role of stem cells in the development of long-term toxicities and carcinogenesis has not received great attention so far, despite growing evidence indicating the relationship of stem cell damage to adverse effects later in life. However, testing this in vitro is a scientific/technical challenge in particular due to the complex interplay of factors existing under physiological conditions. Current major research programs in stem cell toxicity are not aiming to demonstrate that stem cells can be targeted by toxicants. Therefore, this knowledge gap needs to be addressed in additional research activities developing technical solutions and defining appropriate experimental designs. The current review describes selected examples of the role of stem cells in the development of long-term toxicities in the brain, heart or liver and in the development of cancer. The presented examples illustrate the need to analyze the contribution of stem cells to chronic toxicity in order to make a final conclusion whether stem cell toxicities are an underestimated risk in mechanism-based safety assessments. This requires the development of predictive in vitro models allowing the assessment of adverse effects to stem cells on chronic toxicity and carcinogenicity.

The neonicotinoid imidachloprid shows high chronic toxicity to mayfly nymphs

NARCIS (Netherlands)

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

2013-01-01

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

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

International Nuclear Information System (INIS)

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

1993-01-01

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

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

Science.gov (United States)

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.

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

African Journals Online (AJOL)

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

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

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Débora Rebechi

2014-09-01

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

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

International Nuclear Information System (INIS)

Heijerick, D.G.; Regoli, L.; Stubblefield, W.

2012-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-08-15

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

Alkyl PAH in crude oil cause chronic toxicity to early life stages of fish

Energy Technology Data Exchange (ETDEWEB)

Hodson, P.V.; Khan, C.W.; Saravanabhavan, G.; Clarke, L.; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). School of Environmental Studies; Hollebone, B.; Wang, Z. [Environment Canada, Ottawa, ON (Canada). ; Short, J. [National Oceanic and Atmospheric Administration, Juneau, AK (United States). Auke Bay Lab; Lee, K.; King, T. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Centre for Offshore Oil and Gas Environmental Research

2007-07-01

In order to mitigate the risk to fisheries following an offshore oil spill, it is necessary to know the components of crude oil that are toxic. Chronic exposure of early life stages of fish to crude oil causes Blue Sac Disease, a syndrome characterized by induction of the cytochrome P450 (CYP1A) enzyme. In this study, effects-driven fractionation of Alaska North Slope Crude was used to identify the classes of compounds that cause CYP1A induction in juvenile rainbow trout and chronic toxicity to developing stages of Japanese medaka. Four fractions of compounds were created by low temperature vacuum distillation. This separated the constituents of oil according to their volatility within defined temperature ranges. The fractions were separated according to their boiling points. With a temperature range of 287-481 degrees C, fraction F3 was the only fraction as toxic as whole oil and induced CYPP1A enzymes of fish. Fractions containing specific classes of alkyl PAH were also collected. For all separations, the performance of the method was evaluated by the extent to which PAH were separated from aliphatics, resins and waxes, as well as by the quantitative recovery of mass in fractions and subfractions. The induction of CYP1A enzymes showed that PAH was present in all fractions that were highly toxic, but the toxicity tests indicated that not all fractions containing PAH were toxic. This research provided a scientific basis for comparing the risks of different crude oils based on chemical analyses that show the different proportions or amounts of PAH present. The results indicate which compounds of concern should be used to determine the extent and success of oil spill remediation, and provide a biological interpretation of chemical fingerprinting used to discriminate the sources of oil pollution. 15 refs., 1 tab.

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

DEFF Research Database (Denmark)

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

2016-01-01

While differences in silver nanoparticle (AgNP) colloidal stability, surface potential, or acute aquatic toxicity for differently stabilized AgNP have often been reported, these have rarely been studied in long-term ecotoxicity tests. In the current study, we investigated the chronic toxicity of Ag...... types of AgNP during a typical media exchange period in the D. magna test for chronic toxicity. As expected, the sterically stabilized AgNP were more stable in the test medium, also in the presence of food; however, a higher uptake of silver after 24 h exposure of the charge stabilized AgNP was found...... compared to the detergent-stabilized AgNP (0.046 ± 0.006 μg Ag μg DW−1 and 0.023 ± 0.005 μg Ag μg DW−1, respectively). In accordance with this, the higher reproductive effects and mortality were found for the charge-stabilized than for the sterically-stabilized silver nanoparticles in 21-d tests...

Acute and chronic systemic chromium toxicity.

Science.gov (United States)

Gad, S C

1989-10-01

Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.

ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

Science.gov (United States)

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 ...

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

NARCIS (Netherlands)

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

2003-01-01

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

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

NARCIS (Netherlands)

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

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

Acute and chronic toxicity of effluent water from an abandoned uranium mine.

Science.gov (United States)

Antunes, S C; Pereira, R; Gonçalves, F

2007-08-01

Inactive or abandoned mines represent a significant source of environmental, chemical, physical, and aesthetic impact. Among concerning situations, the occurrence of abandoned or semi-abandoned mine-associated ponds (for sedimentation of solids, for effluent neutralization, or for washing the ore) is a common feature in this type of system. These ponds are a source of contamination for the groundwater resources and adjacent soils, because they lack appropriate impermeabilization. The use of this water for agriculture may also pose chronic risks to humans. In Portugal, these problems have been diagnosed and some remediation projects have been developed. The purpose of our study was to evaluate the acute and chronic toxicity of water samples collected from the aquatic system surrounding an abandoned uranium mine (Cunha Baixa, Mangualde, Central Portugal). The present study focuses on the water compartment, whose toxicity was evaluated by means of standard toxicity assays using two Daphnia species (D. longispina and D. magna). Three different ponds were used in the characterization of the aquatic system from Cunha Baixa mine: a reference pond (Ref), a mine effluent treatment pond (T), and a mine pit pond (M). Metal analyses performed in the water samples from these ponds showed values that, in some cases, were much higher than maximum recommendable values established (especially Al, Mn) by Portuguese legislation for waters for crop irrigation. Acute toxicity was only observed in the mine pit pond, with EC(50) values of 28.4% and 50.4% for D. longispina and D. magna, respectively. The significant impairment of chronic endpoints, translated in reductions in the population growth rate for both species, gives rise to concerns regarding the potential risks for aquatic zooplanktonic communities, from local receiving waters, potentially exposed to point source discharges of the treated and nontreated effluent from Cunha Baixa uranium mine.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-07-15

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

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

Directory of Open Access Journals (Sweden)

Yun Wang

2017-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-08-15

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

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

International Nuclear Information System (INIS)

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

2010-01-01

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. - Roundup WeatherMAX may cause extensive mortality among larval New Mexico and Plains spadefoots; it is unlikely that exposure to Ignite 280 SL would result in extensive mortalities.

Toxicity assessment of sodium fluoride in Drosophila melanogaster after chronic sub-lethal exposure.

Science.gov (United States)

Dutta, Moumita; Rajak, Prem; Khatun, Salma; Roy, Sumedha

2017-01-01

Sodium fluoride (NaF), one of the most frequently used fluoride compound is composed of Na + and F - . Apart from its use in water fluoridation, NaF also acts as a major component for different dental products like toothpastes, gels and mouth rinses etc. The present study was carried out to explore the toxic impact of chronic NaF exposure on a non-target organism, Drosophila melanogaster. The larvae exposed to different concentrations of NaF through food showed a significant increase in HSP70 expression both qualitatively and quantitatively. The altered tail length and tail intensity in Comet assay validate the increased DNA damage in treated larvae. The activity of AChE, oxidative stress marker enzymes, phase I and phase II detoxifying enzymes were found to be significantly inhibited in the treated larvae when compared to control though there was no evidence of dose dependent change in each case. The alterations in the mentioned parameters can be due to increased body Fluoride ion (F - ) concentration since the analysis with ion electrode analyzer revealed that F - concentration increased significantly with NaF treatment. Hence, the results suggest that D. melanogaster manifest prominent toxic response when subjected to chronic exposure to sub-lethal NaF concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Amelioration of chronic fluoride toxicity by calcium and fluoride-free water in rats.

Science.gov (United States)

Shankar, Priyanka; Ghosh, Sudip; Bhaskarachary, K; Venkaiah, K; Khandare, Arjun L

2013-07-14

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F - ; low-Ca (0·25 %) diet (LCD), Ca - F - ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca - F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca - F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca - F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca - F - and Ca - F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca - F+/Ca+F - and Ca - F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca - F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.

Alkyl PAH in crude oil cause chronic toxicity to early life stages of fish. Volume 1

Energy Technology Data Exchange (ETDEWEB)

Hodson, P.V.; Khan, C.W.; Saravanabhavan, G.; Clarke, L.; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). School of Environmental Studies; Hollebone, B.; Wang, Z. [Environment Canada, Ottawa, ON (Canada). ; Short, J. [National Oceanic and Atmospheric Administration, Juneau, AK (United States). Auke Bay Lab; Lee, K.; King, T. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Centre for Offshore Oil and Gas Environmental Research

2007-07-01

In order to mitigate the risk to fisheries following an offshore oil spill, it is necessary to know the components of crude oil that are toxic. Chronic exposure of early life stages of fish to crude oil causes Blue Sac Disease, a syndrome characterized by induction of the cytochrome P450 (CYP1A) enzyme. In this study, effects-driven fractionation of Alaska North Slope Crude was used to identify the classes of compounds that cause CYP1A induction in juvenile rainbow trout and chronic toxicity to developing stages of Japanese medaka. Four fractions of compounds were created by low temperature vacuum distillation. This separated the constituents of oil according to their volatility within defined temperature ranges. The fractions were separated according to their boiling points. With a temperature range of 287-481 degrees C, fraction F3 was the only fraction as toxic as whole oil and induced CYPP1A enzymes of fish. Fractions containing specific classes of alkyl PAH were also collected. For all separations, the performance of the method was evaluated by the extent to which PAH were separated from aliphatics, resins and waxes, as well as by the quantitative recovery of mass in fractions and subfractions. The induction of CYP1A enzymes showed that PAH was present in all fractions that were highly toxic, but the toxicity tests indicated that not all fractions containing PAH were toxic. This research provided a scientific basis for comparing the risks of different crude oils based on chemical analyses that show the different proportions or amounts of PAH present. The results indicate which compounds of concern should be used to determine the extent and success of oil spill remediation, and provide a biological interpretation of chemical fingerprinting used to discriminate the sources of oil pollution. 15 refs., 1 tab.

Evaluation of acute and chronic toxicity of DSS and LAS surfactants undergoing the irradiation with electron beam

International Nuclear Information System (INIS)

Romanelli, Maria Fernanda

2004-01-01

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

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

NARCIS (Netherlands)

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

2009-01-01

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

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

NARCIS (Netherlands)

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

2009-01-01

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

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

Science.gov (United States)

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

2017-01-01

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

Critical Limits for Hg(II) in soils, derived from chronic toxicity data

International Nuclear Information System (INIS)

Tipping, E.; Lofts, S.; Hooper, H.; Frey, B.; Spurgeon, D.; Svendsen, C.

2010-01-01

Published chronic toxicity data for Hg(II) added to soils were assembled and evaluated to produce a data set comprising 52 chronic end-points, five each for plants and invertebrates and 42 for microbes. With end-points expressed in terms of added soil Hg(II) contents, Critical Limits were derived from the 5th percentiles of species sensitivity distributions, values of 0.13 μg (g soil) -1 and 3.3 μg (g soil organic matter) -1 being obtained. The latter value exceeds the currently recommended Critical Limit, used to determine Hg(II) Critical Loads in Europe, of 0.5 μg (g soil organic matter) -1 . We also applied the WHAM/Model VI chemical speciation model to estimate concentrations of Hg 2+ in soil solution, and derived an approximate Critical Limit Function (CLF) that includes pH; log [Hg 2+ ] crit = -2.15 pH -17.10. Because they take soil properties into account, the soil organic matter-based limit and the CLF provide the best assessment of toxic threat for different soils. For differing representative soils, each predicts a range of up to 100-fold in the dry weight-based content of mercury that corresponds to the Critical Limit. - Published laboratory toxicity data and chemical speciation modelling are used to derive Critical Limits expressed as either soil Hg(II) content or Hg 2+ concentration.

Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.

Science.gov (United States)

Keshavarzi, Behnam; Seradj, Afsaneh; Akbari, Zahra; Moore, Farid; Shahraki, Alireza Rahmani; Pourjafar, Mehrdad

2015-07-01

After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and Babanazar villages in Kurdistan province, the concentration of this element in drinking water, cultivated soil, alfalfa hay, wool, and blood samples was evaluated. Total As concentrations ranged from 119 to 310 μg/L in drinking water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg in sheep's wool, and 86.30-656 μg/L in blood samples. These very high As contents, in all parts of the biogeochemical cycle, exceed the recommended normal range for this element compared with a control area. Results indicate that As has moved through all compartments of the biogeochemical cycle by way of direct or indirect pathways. The present investigation illustrated decreased packed cell volume and hemoglobin in sheep from the As-contaminated zone. It was concluded that sheep from the contaminated areas suffer from anemia. Chronic As exposure of the liver was determined by liver function tests. For this purpose, blood aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The results show that serum ALT and AST activities are increased significantly (p < 0.01) in the sheep population exposed to As in the contaminated zone. Moreover, chronic As exposure causes injury to hepatocytes and damages the liver.

Acute and chronic toxicity study of the water accommodated fraction (WAF), chemically enhanced WAF (CEWAF) of crude oil and dispersant in the rock pool copepod Tigriopus japonicus.

Science.gov (United States)

Lee, Kyun-Woo; Shim, Won Joon; Yim, Un Hyuk; Kang, Jung-Hoon

2013-08-01

We determined the toxicity of the water accommodated hydrocarbon fraction (WAF), two chemically enhanced WAFs (CEWAFs; CEWAF-C, Crude oil+Corexit 9500 and CEWAF-H, Crude oil+Hiclean) of crude oil and two dispersants (Corexit 9500 and Hiclean) to the rock pool copepod Tigriopus japonicus. In the acute toxicity test, Corexit 9500 was the most toxic of all the chemicals studied. The nauplius stage of T. japonicus was more susceptible to the toxic chemicals studied than the adult female. The toxicity data using the nauplius stage was then considered as baseline to determine the spiking concentration of chemicals for chronic toxicity tests on the copepod. As the endpoints in the chronic toxicity test, survival, sex ratio, developmental time and fecundity of the copepod were used. All chemicals used in this study resulted in increased toxicity in the F1 generation. The lowest-observed-adverse-effect (LOAE) concentrations of WAF, CEWAF-H, CEWAF-C, Hiclean and Corexit 9500 were observed to be 50%, 10%, 0.1%, 1% and 1%, respectively. The results in present study imply that copepods in marine may be negatively influenced by spilled oil and dispersant. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chronic toxicity of fumonisins in turkeys.

Science.gov (United States)

Tardieu, D; Bailly, J-D; Skiba, F; Métayer, J-P; Grosjean, F; Guerre, P

2007-09-01

Fumonisins are mycotoxins that are found worldwide. They are mainly produced by Fusarium verticillioides during its development on corn. The main toxic effects of these molecules have been well characterized in poultry in the case of acute exposure, but the subclinical and economic effects of chronic exposure are less known. Whereas the latest European recommendations suggest that maximal levels of fumonisins in corn could reach 60 mg/kg and the maximal contamination of poultry feeds could reach 20 mg/kg, no study is available at this level in turkeys. The aim of the present work was thus to characterize the effects of exposure to fumonisins (concentrations of 0, 5, 10, and 20 mg of fumonisin B1 + fumonisin B2/kg of feed) on feed consumption and growth in turkeys over a period of 9 wk. Main biochemical parameters of the liver and alteration of sphingolipid metabolism were investigated in plasma, liver, and kidney. The main results showed no effect on feed consumption and growth in exposed turkeys. Moreover, no effect was observed on the weight of tissues and markers of liver injury. By contrast, a disruption of sphingolipid metabolism was clear at a level of exposure of 10 and 20 mg of fumonisin B1 + fumonisin B2 mg/kg of feed. Both hepatic and kidney concentrations of sphinganine increased gradually throughout the exposure period. These results reveal that disruption of sphingolipid metabolism is an early and sensitive biomarker of fumonisins exposure in turkeys; the consequences on these alterations remain to be established.

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

Science.gov (United States)

Farag, Aïda M.; Harper, David D.

2014-01-01

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

Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

Science.gov (United States)

Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

2015-02-01

Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs. Copyright © 2014 Elsevier B.V. All rights reserved.

Critical Limits for Hg(II) in soils, derived from chronic toxicity data

Energy Technology Data Exchange (ETDEWEB)

Tipping, E., E-mail: et@ceh.ac.u [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Lofts, S. [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Hooper, H. [Centre for Ecology and Hydrology, Wallingford, OX10 8BB (United Kingdom); Frey, B. [Swiss Federal Research Institute WSL, 8903 Birmensdorf (Switzerland); Spurgeon, D.; Svendsen, C. [Centre for Ecology and Hydrology, Wallingford, OX10 8BB (United Kingdom)

2010-07-15

Published chronic toxicity data for Hg(II) added to soils were assembled and evaluated to produce a data set comprising 52 chronic end-points, five each for plants and invertebrates and 42 for microbes. With end-points expressed in terms of added soil Hg(II) contents, Critical Limits were derived from the 5th percentiles of species sensitivity distributions, values of 0.13 {mu}g (g soil){sup -1} and 3.3 {mu}g (g soil organic matter){sup -1} being obtained. The latter value exceeds the currently recommended Critical Limit, used to determine Hg(II) Critical Loads in Europe, of 0.5 {mu}g (g soil organic matter){sup -1}. We also applied the WHAM/Model VI chemical speciation model to estimate concentrations of Hg{sup 2+} in soil solution, and derived an approximate Critical Limit Function (CLF) that includes pH; log [Hg{sup 2+}]{sub crit} = -2.15 pH -17.10. Because they take soil properties into account, the soil organic matter-based limit and the CLF provide the best assessment of toxic threat for different soils. For differing representative soils, each predicts a range of up to 100-fold in the dry weight-based content of mercury that corresponds to the Critical Limit. - Published laboratory toxicity data and chemical speciation modelling are used to derive Critical Limits expressed as either soil Hg(II) content or Hg{sup 2+} concentration.

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

NARCIS (Netherlands)

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

2016-01-01

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

Quantitative structure–activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes)

Energy Technology Data Exchange (ETDEWEB)

Lin, Hongkang [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Morandi, Garrett D. [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Brown, R. Stephen [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Snieckus, Victor; Rantanen, Toni [Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Jørgensen, Kåre B. [Department of Mathematics and Natural Sciences, University of Stavanger, 4036 Stavanger (Norway); Hodson, Peter V., E-mail: peter.hodson@queensu.ca [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada)

2015-02-15

Highlights: • Medaka embryos were exposed to alkyl chrysenes and benzo[a]anthracenes (BAA). • Concentrations were kept constant by partition controlled delivery. • Chrysene was not toxic within solubility limits, in contrast to BAA. • Alkylation increased the toxicity of chrysene and BAA. • Toxicity was related to hydrophobicity and to specific modes of action. - Abstract: Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and log K{sub ow} values provided a rough estimation of structure–activity relationships for alkyl-PAHs, but K{sub ow} alone did not provide

Late toxicity in breast cancer radiotherapy

International Nuclear Information System (INIS)

Gonzalez Coletti, F.; Rafailovici, L.; Filomia, M.L.; Chiozza, J.; Dosoretz, B.

2008-01-01

Full text: The aim of this study is to describe and classify chronic complications due to radiotherapy in breast cancer. Also the impact of radiotherapy on the quality of life of patients is evaluated. Materials and methods: 50 patients with breast cancer at early stages (78% in situ, 22% I and II) treated with radiotherapy in breast volume plus boost (45/50 Gy + 18/20 Gy) with a follow up over 5 years. Acute toxicities were found retrospectively and chronic toxicities were assessed though physical examination and review of complementary studies. To facilitate data collection, pre printed forms were used. Bibliographic searches were made. Results: 10% received chemotherapy and 64% tamoxifen. The predominant chronic toxicity were found in skin (66%), although grade I and II (hyperpigmentation 26%, dryness 22%, telangiectasia 10% fibrosis, 4%, other 4%). A 50% of the patients showed hypoesthesia in ipsilateral upper limb. The other toxicities were presented in low rate and magnitude: mastodynia 16%; actinic pneumonitis 4%, pyrosis 4%, Tachycardia 2%, among others. Of the patients with acute toxicity, only 30% were grade III. The 70% of the patients had a positive impact of radiotherapy on quality of life. Conclusions: We found low rates and degrees of late toxicity. It was noticed a relationship between acute and chronic toxicity, because those who presented adverse effects during treatment developed late effects. It reflects the importance of integrating monitoring as part of radiation treatment. It should be adopted a single score of late toxicity measurement to unify data from different series. (authors) [es

Biochemistry of hemlock (Conium maculatum L.) alkaloids and their acute and chronic toxicity in livestock. A review.

Science.gov (United States)

López, T A; Cid, M S; Bianchini, M L

1999-06-01

The literature on Conium maculatum biochemistry and toxicology, dispersed in a large number of scientific publications, has been put together in this review. C. maculatum is a weed known almost worldwide by its toxicity to many domestic animals and to human beings. It is an Umbelliferae, characterized by long, hollow stems, reaching up to 2 m height at maturity, producing a large amount of lush foliage during its vegetative growth. Its flowers are white, grouped in umbels formed by numerous umbellules. It produces a large number of seeds that allow the plant to form thick stands in modified soils, sometimes encroaching on cultivated fields, to the extent of impeding the growth of any other vegetation inside the C. maculatum area of growth. Eight piperidinic alkaloids have been identified in this species. Two of them, gamma-coniceine and coniine are generally the most abundant and they account for most of the plant acute and chronic toxicity. These alkaloids are synthesized by the plant from eight acetate units from the metabolic pool, forming a polyketoacid which cyclises through an aminotransferase and forms gamma-coniceine as the parent alkaloid via reduction by a NADPH-dependent reductase. The acute toxicity is observed when animals ingest C. maculatum vegetative and flowering plants and seeds. In a short time the alkaloids produce a neuromuscular blockage conducive to death when the respiratory muscles are affected. The chronic toxicity affects only pregnant animals. When they are poisoned by C. maculatum during the fetuses organ formation period, the offspring is born with malformations, mainly palatoschisis and multiple congenital contractures (MCC; frequently described as arthrogryposis). Acute toxicity, if not lethal, may resolve in the spontaneous recovery of the affected animals provided further exposure to C. maculatum is avoided. It has been observed that poisoned animals tend to return to feed on this plant. Chronic toxicity is irreversible and

The Effects of Elevated Specific Conductivity on the Chronic Toxicity of Mining Influenced Streams Using Ceriodaphnia dubia.

Science.gov (United States)

Armstead, Mindy Yeager; Bitzer-Creathers, Leah; Wilson, Mandee

2016-01-01

Salinization of freshwater ecosystems as a result of human activities has markedly increased in recent years. Much attention is currently directed at evaluating the effects of increased salinity on freshwater biota. In the Central Appalachian region of the eastern United States, specific conductance from alkaline discharges associated with mountain top mining practices has been implicated in macroinvertebrate community declines in streams receiving coal mining discharges. Whole effluent toxicity testing of receiving stream water was used to test the hypothesis that mine discharges are toxic to laboratory test organisms and further, that toxicity is related to ionic concentrations as indicated by conductivity. Chronic toxicity testing using Ceriodaphnia dubia was conducted by contract laboratories at 72 sites with a total of 129 tests over a 3.5 year period. The database was evaluated to determine the ionic composition of mine effluent dominated streams and whether discharge constituents were related to toxicity in C. dubia. As expected, sulfate was found to be the dominant anion in streams receiving mining discharges with bicarbonate variable and sometimes a substantial component of the dissolved solids. Overall, the temporal variability in conductance was low at each site which would indicate fairly stable water quality conditions. Results of the toxicity tests show no relationship between conductance and survival of C. dubia in the mining influenced streams with the traditional toxicity test endpoints. However, consideration of the entire dataset revealed a significant inverse relationship between conductivity and neonate production. While conductivity explained very little of the high variability in the offspring production (r2 = 0.1304), the average numbers of offspring were consistently less than 20 neonates at the highest conductivities.

The Effects of Elevated Specific Conductivity on the Chronic Toxicity of Mining Influenced Streams Using Ceriodaphnia dubia.

Directory of Open Access Journals (Sweden)

Mindy Yeager Armstead

Full Text Available Salinization of freshwater ecosystems as a result of human activities has markedly increased in recent years. Much attention is currently directed at evaluating the effects of increased salinity on freshwater biota. In the Central Appalachian region of the eastern United States, specific conductance from alkaline discharges associated with mountain top mining practices has been implicated in macroinvertebrate community declines in streams receiving coal mining discharges. Whole effluent toxicity testing of receiving stream water was used to test the hypothesis that mine discharges are toxic to laboratory test organisms and further, that toxicity is related to ionic concentrations as indicated by conductivity. Chronic toxicity testing using Ceriodaphnia dubia was conducted by contract laboratories at 72 sites with a total of 129 tests over a 3.5 year period. The database was evaluated to determine the ionic composition of mine effluent dominated streams and whether discharge constituents were related to toxicity in C. dubia. As expected, sulfate was found to be the dominant anion in streams receiving mining discharges with bicarbonate variable and sometimes a substantial component of the dissolved solids. Overall, the temporal variability in conductance was low at each site which would indicate fairly stable water quality conditions. Results of the toxicity tests show no relationship between conductance and survival of C. dubia in the mining influenced streams with the traditional toxicity test endpoints. However, consideration of the entire dataset revealed a significant inverse relationship between conductivity and neonate production. While conductivity explained very little of the high variability in the offspring production (r2 = 0.1304, the average numbers of offspring were consistently less than 20 neonates at the highest conductivities.

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

Science.gov (United States)

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

2017-07-01

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

Toxicity of fluoride to aquatic species and evaluation of toxicity modifying factors.

Science.gov (United States)

Pearcy, Krysta; Elphick, James; Burnett-Seidel, Charlene

2015-07-01

The present study was performed to investigate the toxicity of fluoride to a variety of freshwater aquatic organisms and to establish whether water quality variables contribute substantively to modifying its toxicity. Water hardness, chloride, and alkalinity were tested as possible toxicity modifying factors for fluoride using acute toxicity tests with Hyalella azteca and Oncorhynchus mykiss. Chloride appeared to be the major toxicity modifying factor for fluoride in these acute toxicity tests. The chronic toxicity of fluoride was evaluated with a variety of species, including 3 fish (Pimephales promelas, O. mykiss, and Salvelinus namaycush), 3 invertebrates (Ceriodaphnia dubia, H. azteca, and Chironomus dilutus), 1 plant (Lemna minor), and 1 alga (Pseudokirchneriella subcapitata). Hyalella azteca was the most sensitive species overall, and O. mykiss was the most sensitive species of fish. The role of chloride as a toxicity modifying factor was inconsistent between species in the chronic toxicity tests. © 2015 SETAC.

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

Directory of Open Access Journals (Sweden)

Pongri Adarki

2017-09-01

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

Downbeat nystagmus as a result of lamotrigine toxicity.

Science.gov (United States)

Alkawi, Ammar; Kattah, Jorge C; Wyman, Katie

2005-02-01

Downbeat nystagmus (DBN) has been reported with phenytoin and carbamazepine toxicity. DBN has not been described as a result of lamotrigine toxicity. Clinical records, neuroimaging and video recordings were obtained in two patients diagnosed with intractable epilepsy who developed oscillopsia and incoordination while being treated with lamotrigine. One patient had a videonystagmographic (VNG) study. Lamotrigine's half-life is extended when used with valproic acid; hence, the increased chance of neurotoxicity associated with DBN. In our cases, DBN and truncal ataxia occurred in conjunction with toxic lamotrigine serum levels. Anticonvulsant toxicity should be considered as a cause of DBN. Lamotrigine toxicity may be an unusual cause.

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

International Nuclear Information System (INIS)

Okunieff, Paul; Xu Jianhua; Hu Dongping; Liu Weimin; Zhang Lurong; Morrow, Gary; Pentland, Alice; Ryan, Julie L.; Ding, Ivan M.D.

2006-01-01

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]-α, and lymphotoxin-β) or fibrogenic cytokines (transforming growth factor [TGF]-β) 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-α, and lymphotoxin-β) and the fibrogenic cytokine, TGF-β, 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

Comparison of the capacity of two biotic ligand models to predict chronic copper toxicity to two Daphnia magna clones and formulation of a generalized bioavailability model.

Science.gov (United States)

Van Regenmortel, Tina; Janssen, Colin R; De Schamphelaere, Karel A C

2015-07-01

Although it is increasingly recognized that biotic ligand models (BLMs) are valuable in the risk assessment of metals in aquatic systems, the use of 2 differently structured and parameterized BLMs (1 in the United States and another in the European Union) to obtain bioavailability-based chronic water quality criteria for copper is worthy of further investigation. In the present study, the authors evaluated the predictive capacity of these 2 BLMs for a large dataset of chronic copper toxicity data with 2 Daphnia magna clones, termed K6 and ARO. One BLM performed best with clone K6 data, whereas the other performed best with clone ARO data. In addition, there was an important difference between the 2 BLMs in how they predicted the bioavailability of copper as a function of pH. These modeling results suggested that the effect of pH on chronic copper toxicity is different between the 2 clones considered, which was confirmed with additional chronic toxicity experiments. Finally, because fundamental differences in model structure between the 2 BLMs made it impossible to create an average BLM, a generalized bioavailability model (gBAM) was developed. Of the 3 gBAMs developed, the authors recommend the use of model gBAM-C(uni), which combines a log-linear relation between the 21-d median effective concentration (expressed as free Cu(2+) ion activity) and pH, with more conventional BLM-type competition constants for sodium, calcium, and magnesium. This model can be considered a first step in further improving the accuracy of chronic toxicity predictions of copper as a function of water chemistry (for a variety of Daphnia magna clones), even beyond the robustness of the current BLMs used in regulatory applications. © 2015 SETAC.

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

Science.gov (United States)

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

2013-08-01

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

Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration

Energy Technology Data Exchange (ETDEWEB)

Pixberg, Caroline [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Koch, Raphael [Institute of Biostatistics and Clinical Research, University of Muenster, Muenster (Germany); Eich, Hans Theodor, E-mail: Hans.Eich@ukmuenster.de [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Department of Radiation Oncology, University of Koeln, Koeln (Germany); Martinsson, Ulla [Department of Oncology, University Hospital, Uppsala (Sweden); Kristensen, Ingrid [Department of Radiation Physics, Skåne University Hospital, Lund (Sweden); Matuschek, Christiane [Department of Radiation Oncology, University Hospital of Duesseldorf, Duesseldorf (Germany); Kortmann, Rolf-Dieter [Department of Radiation Oncology, University Hospital of Leipzig, Leipzig (Germany); Pohl, Fabian [Department of Radiation Oncology, University of Regensburg, Regensburg (Germany); Elsayad, Khaled [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Christiansen, Hans [Department of Radiation Oncology, Medical School Hannover, Hannover (Germany); Willich, Normann [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Lindh, Jack [Department of Radiation Sciences, Umeå University, Umeå (Sweden); Steinmann, Diana [Department of Radiation Oncology, University Hospital of Muenster, Muenster (Germany); Department of Radiation Oncology, Medical School Hannover, Hannover (Germany)

2016-03-15

Purpose: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae. Materials and Methods: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: As of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity. Conclusions: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute

Hepatic toxicity assessment of cationic liposome exposure in healthy and chronic alcohol fed mice

DEFF Research Database (Denmark)

Kermanizadeh, Ali; Jacobsen, Nicklas R.; Roursgaard, Martin

2017-01-01

or chronically alcohol fed mice. Additionally, the in vitro material-induced adverse effects (cytotoxicity, inflammation or albumin secretion) were all also minimal. The data from this study demonstrated that the intravenous injection of cationic liposomes does not cause hepatic toxicity. This investigation......, the question of potential toxicological effects needs to be addressed. In the present investigation, a cationic liposome with prospective for medical applications was constructed and thoroughly assessed for any material-induced hepatic adverse effects in vivo − in healthy and alcoholic hepatic disease models...... is important as it investigates the toxicity of a nano-sized material in a model of alcoholic hepatic disease in vitro and in vivo. This is an area of research in the field of nanotoxicology that is currently almost entirely overlooked....

FLUORIDE TOXICITY – A HARSH REALITY

OpenAIRE

Bandlapalli Pavani; Mandava Ragini; David Banji; Otilia J F Banji; N Gouri Pratusha

2011-01-01

There are many incidents of fluoride toxicity whether it is acute or chronic. Fluoride toxicity is an environmental hazard which arises from the upper layers of geological crust and is dissolved in water. Prolonged drinking of such water causes chronic fluoride toxicity. Use of fluoride containing compounds for various purposes such as dental products, metal, glass, refrigerator and chemical industries act as a source of fluoride poisoning and increase the risk of toxicity. This review reflec...

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

Science.gov (United States)

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

2017-09-01

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

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

DEFF Research Database (Denmark)

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

2015-01-01

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

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

Directory of Open Access Journals (Sweden)

Pamela eMaher

2015-12-01

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

National Air Toxic Assessments (NATA) Results

Data.gov (United States)

U.S. Environmental Protection Agency — The National Air Toxics Assessment was conducted by EPA in 2002 to assess air toxics emissions in order to identify and prioritize air toxics, emission source types...

Acute and chronic toxicity of sediment samples from Guanabara Bay (RJ during the rainy period

Directory of Open Access Journals (Sweden)

Luciane Alves Maranho

2010-06-01

Full Text Available Guanabara Bay is a marine-estuarine environment of high ecological and socio-economic importance, subject to a variety of environmental impacts. Sediment is the eventual repository for most substances introduced into water bodies and may, therefore, provide an integrated measure of the environmental quality, which can be assessed by many different approaches. In this project, the quality of sediments from Guanabara Bay was evaluated by the ecotoxicological approach: whole-sediment toxicity tests, using Tiburonella viscana, and porewater, elutriate and sediment-water interface chronic toxicity tests, using embryos of Lytechinus variegatus, were applied. Sediments were collected at 14 sampling stations, distributed across the bay. Chronic tests showed significant toxicity in most of the sediment samples. Sediments from stations 1, 2, 3, 6, 8, 10, 11, 12 and 15 showed acute toxicity as well. The results of the different tests were well correlated, and their integration showed that the sediments analyzed were considered unsuitable for aquatic life, resulting in the environmental degradation of Guanabara Bay. In this context, the control of pollution sources and multi-purpose management are required to improve the environmental quality.A Baía de Guanabara é um ambiente marinho-estuarino de grande relevância ecológica e sócio-econômica, e sujeita a uma ampla gama de impactos ambientais. O sedimento é o principal destino para a maioria das substâncias introduzidas nos corpos d'água, podendo fornecer uma medida integrada da qualidade ambiental, a qual pode ser avaliada por várias abordagens. Neste projeto, a qualidade de sedimentos da Baía de Guanabara foi por uma abordagem ecotoxicológica, por meio de testes de toxicidade aguda de sedimento integral, utilizando Tiburonella viscana, e testes de toxicidade crônica de água intersticial, elutriato e interface sedimento-água, utilizando embriões de Lytechinus variegatus. Os sedimentos foram

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion.

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Thurlow, John S; Little, Dustin J; Baker, Thomas P; Yuan, Christina M

2013-06-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion.

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

Science.gov (United States)

Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

2013-01-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ∼5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose chronic exposure. This case represents possible sequelae of chronic potassium chlorate ingestion. PMID:26064493

Acute toxicity from baking soda ingestion.

Science.gov (United States)

Thomas, S H; Stone, C K

1994-01-01

Sodium bicarbonate is an extremely well-known agent that historically has been used for a variety of medical conditions. Despite the widespread use of oral bicarbonate, little documented toxicity has occurred, and the emergency medicine literature contains no reports of toxicity caused by the ingestion of baking soda. Risks of acute and chronic oral bicarbonate ingestion include metabolic alkalosis, hypernatremia, hypertension, gastric rupture, hyporeninemia, hypokalemia, hypochloremia, intravascular volume depletion, and urinary alkalinization. Abrupt cessation of chronic excessive bicarbonate ingestion may result in hyperkalemia, hypoaldosteronism, volume contraction, and disruption of calcium and phosphorus metabolism. The case of a patient with three hospital admissions in 4 months, all the result of excessive oral intake of bicarbonate for symptomatic relief of dyspepsia is reported. Evaluation and treatment of patients with acute bicarbonate ingestion is discussed.

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

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Farzamfar B

2008-04-01

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

Acute and chronic toxicity of copper to the euryhaline rotifer, Brachionus plicatilis ("L" strain).

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Arnold, W R; Diamond, R L; Smith, D S

2011-02-01

This article presents data from original research, intended for the use in the development of copper (Cu) criteria for the protection of estuarine and marine organisms and their uses in the United States. Two 48-h static-acute toxicity tests-one with and one without added food-and a 96-h static multigeneration life-cycle test (P1-F2 generations) were performed concurrently using the euryhaline rotifer Brachionus plicatilis ("L" strain) to develop a Cu acute-to-chronic ratio (ACR) for this species. Tests were performed at 15 g/L salinity, at 25°C, and the exposure concentrations of dissolved Cu were verified. Supplemental chemical analyses were performed and reported for the development of a Cu-saltwater biotic ligand model (BLM). Supplemental analyses included alkalinity, calcium, chloride, dissolved organic carbon (DOC), hardness, magnesium, potassium, sodium, and temperature. The acute toxicity test measurement end points were the dissolved Cu median lethal concentration (LC₅₀) values based on rotifer survival. The chronic measurement end points were the dissolved Cu no-observed-effect concentration (NOEC), lowest-observed-effect concentration (LOEC), EC₂₅, EC₂₀, and EC₁₀ based on the intrinsic rate of rotifer population increase (r). The 48-h LC₅₀(Fed), 48-h LC₅₀(Unfed), 96-h NOEC, 96-h LOEC, EC₂₅, EC₂₀, and EC₁₀ were 20.8, 13.4, 6.1, 10.3, 11.7, 10.9, and 8.8 μg Cu/L, respectively. The ACRs were calculated as ratios of each 48-h LC₅₀ value [fed and unfed) and each of the 96-h chronic values (ChV; geometric mean of NOEC and LOEC)], EC₁₀, EC₂₀, and EC₂₅. The ACRs ranged from 1.15 to 2.63.

Toxic Effects of Cannabis and Cannabinoids: Animal Data

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Pierre Beaulieu

2005-01-01

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

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

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

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

Science.gov (United States)

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. © 2014 SETAC.

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

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

2016-11-01

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

Evaluation of uptake and chronic toxicity of virgin polystyrene microbeads in freshwater zebra mussel Dreissena polymorpha (Mollusca: Bivalvia).

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Magni, Stefano; Gagné, François; André, Chantale; Della Torre, Camilla; Auclair, Joëlle; Hanana, Houda; Parenti, Camilla Carla; Bonasoro, Francesco; Binelli, Andrea

2018-08-01

Microplastics (MPs), plastic debris smaller than 5mm, are widely found in both marine and freshwater ecosystems. However, few studies regarding their hazardous effects on inland water organisms, have been conducted. For this reason, the aim of our research was the evaluation of uptake and chronic toxicity of two mixtures (MIXs) of virgin polystyrene microbeads (PMs) of 10μm and 1μm in size (MIX 1, with 5×10 5 of 1μmsizePMs/L and 5×10 5 of 10μmsizePMs/L, and MIX 2 with 2×10 6 of 1μmsizePMs/L and 2×10 6 of 10μmsizePMs/L) on freshwater zebra mussel Dreissena polymorpha (Mollusca: Bivalvia) during 6 exposure days. The PM uptake in the mussel body and hemolymph was assessed using confocal microscopy, while the chronic toxicity of PMs was evaluated on exposed mussels using a comprehensive battery of biomarkers of cellular stress, oxidative damage and neuro- genotoxicity. Confocal microscopy analyses showed that MPs concentrated in the gut lumen of exposed mussels, absorbed and transferred firstly in the tissues and then in the hemolymph. The results revealed that PMs do not produce oxidative stress and genetic damage, with the exception of a significant modulation of catalase and glutathione peroxidase activities in mussels exposed to MIX 1. Regarding neurotoxicity, we observed only a significant increase of dopamine concentration in mussels exposed to both MIXs, suggesting a possible implication of this neurotransmitter in an elimination process of accumulated PMs. This research represents a first study about the evaluation of virgin MP toxicity in zebra mussel and more research is warranted concerning the long term neurological effects of virgin MPs. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Development of Alternatives to Chronic Ecotoxicity Tests: Predicting Early-life Stage and Endocrine-mediated Toxicity in Aquatic Vertebrate Species

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In June 2010, the ILSI Health and Environmental Sciences Institute (HESI) with support from sanofi-aventis, NC3Rs, the Humane Society, L’Oreal, and ECVAM, held a workshop aimed at examining critical science needs related to the development of alternatives to chronic fish toxicity...

Acute and chronic toxicity of aluminum to a unionid mussel (Lampsilis siliquoidea) and an amphipod (Hyalella azteca) in water‐only exposures

Science.gov (United States)

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

2018-01-01

The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity data set to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about their sensitivity to Al. The objective of the present study was to evaluate acute 96‐h and chronic 28‐d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3. The acute 50% effect concentration (EC50) for survival of both species was >6200 μg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al data set for freshwater species at a pH range of 5.0 to based on dry weight was 163 μg total Al/L for the mussel and 409 μg total Al/L for the amphipod. Addition of the EC20s to the USEPA chronic Al data set for pH 5.0 to of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. 

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

Science.gov (United States)

Varano, Valentina; Fabbri, Elena; Pasteris, Andrea

2017-08-01

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

Clinical results and toxicity for short-course preoperative radiotherapy and total mesorectal excision in rectal cancer patients

International Nuclear Information System (INIS)

Sterzing, Florian; Jensen, Alexandra; Debus, Jürgen; Hoehle, Frieder; Ulrich, Alexis; Muenter, Marc

2015-01-01

Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009. Local control and survival were analyzed. Chronic adverse effects for 154 patients without local relapse were evaluated according to the NCI–CTCAE version 4.0 classification, with a median follow-up of 48 months. We found a 5-year disease-free survival (DFS) and overall survival (OS) of 71%. The 5-year estimated local control (LC) rate was 94%. A positive resection margin was found in 4% of the patients and was significantly correlated with decreased DFS, OS and LC. Chronic adverse effects were reported by 58% of the patients, of which 10% were Grade 3 toxicities. The most frequent Grade 2 toxicity was stool incontinence (13%). Sexual dysfunction was found in 36% of the patients (31% Grade 1 or 2, and only 5% Grade 3). SCPRT combined with TME produced excellent LC rates together with a low rate of high-grade chronic adverse effects. (author)

Assessment of the Toxicity of Sub-chronic Low and High Doses of the Bio-insecticide Spinosad on the Liver, Kidney and the Cerebellum in Male Albino Mice

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Sabry A El-Naggar

2017-06-01

Full Text Available ABSTRACT Spinosad (SPD is a highly selective insect control product. However, it was reported that SPD has toxicity toward other non-target organisms. This study was conducted to address the toxic effect of two sub-chronic low and high doses; 35 and 350 mg/kg SPD on some biochemical, histological and immunohistochemical parameters of the liver, kidney and cerebellum. Thirty-six male Swiss mice were divided into three groups of 12 mice each; first group (G1 served as a control, second group (G2 received a low sub-chronic dose of SPD that is equal to 35 mg/kg, and third group (G3 received a high sub-chronic dose of SPD that is equal to 350 mg/kg. The results showed that mice which were received 350 mg/kg SPD showed a significant decrease in the body weight and a significant increase in their relative kidney and spleen weights. They also showed a significant increase in alanine aminotransferase (ALT, triglycerides and urea levels. Histopathological examination showed cytoplasmic degeneration and cell necrosis in the liver and kidney. Immunohistochemical examination showed that cerebellum illustrated several neurodegenerative changes and a down-regulation of synaptophysin-Syp. In conclusion, exposure to a high dose of SPD that is equal to 350 mg/kg could cause a marked toxicity on the liver, kidney and cerebellum in male albino mice.

Cerebral CT appearances of toxic encephalopathy of tetramine

International Nuclear Information System (INIS)

Zheng Wenlong; Wu Aiqin; Xu Chongyong; Ying Binyu; Hong Ruizhen

2003-01-01

Objective: To investigate the cerebral CT appearances of toxic encephalopathy of tetramine and improve the recognition on this disease. Methods: Four cases of toxic encephalopathy of tetramine were collected and their cerebral CT appearances were retrospectively analyzed. Results: Cerebral CT appearances in acute phase (within 8 days): (1) cerebral edema in different degree. CT abnormalities consisted of cortical hypodensities and complete loss of gray-white matter differentiation. The CT value were in 11-13 HU, and to be watery density in serious case, (2) subarachnoid hemorrhage. It demonstrated the signs of poisoning hypoxic ischemic encephalopathy in chronic phase. Conclusion: The cerebral CT appearances of toxic encephalopathy of tetramine had some character in acute phase and it can predict the serious degree of intoxication, but there was no characteristic findings in chronic phase

Chronic uranium exposure and growth toxicity for phytoplankton. Dose-effect relationship: first comparison of chemical and radiological toxicity

International Nuclear Information System (INIS)

Gilbin, R.; Pradines, C.; Garnier-Laplace, J.

2004-01-01

The bioavailability of uranium for freshwater organisms, as for other dissolved metals, is closely linked to chemical speciation in solution (U aqueous speciation undergoes tremendous changes in the presence of ligands commonly found in natural waters e.g. carbonate, phosphate, hydroxide and natural organic matter). For the studied chemical domain, short-term uranium uptake experiments have already shown that the free uranyl ion concentration [UO 2 2+ ] is a good predictor of uranium uptake by the green algae Chlamydomonas reinhardtii, as predicted by the Free Ion Activity Model. In agreement with these results, acidic pH and low ligands concentrations in water enhance uranium bioavailability and consequently its potential chronic effects on phytoplankton. Moreover, uranium is known to be both radio-toxic and chemo-toxic. The use of different isotopes of uranium allows to expose organisms to different radiological doses for the same molar concentration: e.g. for a given element concentration (chemical dose), replacing depleted U by U-233 obviously leads to an enhanced radiological delivered dose to organisms (x10 4 ). In this work we established relationships between uranium doses (depleted uranium and 233-U ) and effect on the growth rate of the green algae Chlamydomonas reinhardtii. Uranium bioaccumulation was also monitored. Growth rate was measured both in classical batch (0-72 hrs) and continuous (turbidostat) cultures, the latter protocol allowing medium renewal to diminish exudates accumulation and speciation changes in the medium. The differences in effects will be, if possible, related to the development of defence mechanisms against the formation of reactive oxygen species (forms of glutathione) and the production of phyto-chelatins (small peptides rich in cystein that play an important role in the homeostasis and the detoxication of metals in cells). (author)

Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia.

Science.gov (United States)

El-Ansary, Afaf K; Bacha, Abir Ben; Ayahdi, Layla Y Al-

2011-09-01

This study aims to clarify the relationship between blood Pb(2+) concentration as a ubiquitous environmental pollutant and plasma neurotransmitters as biochemical parameters that reflect brain function in Saudi autistic patients. RBC's lead content together with plasma concentration of gamma aminobutyric acid (GABA), serotonin (5HT) and dopamine (DA) were measured in 25 Saudi autistic patients and compared to 16 age-matching control samples. The obtained data recorded that Saudi autistic patients have a remarkable higher levels of Pb(2+) and significantly elevated levels of GABA, 5HT and DA compared to healthy subjects. ROC analysis revealed satisfactory values of specificity and sensitivity of the measured parameters. This study suggests that postnatal lead toxicity in autistic patients of Saudi Arabia could represent a causative factor in the pathogenesis of autism. Elevated GABA, 5HT and DA were discussed in relation to the chronic lead toxicity recorded in the investigated autistic samples. Copyright © 2011. Published by Elsevier Inc.

Acute and chronic toxicity of aluminum to a unionid mussel (Lampsilis siliquoidea) and an amphipod (Hyalella azteca) in water‐only exposures

Science.gov (United States)

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

2018-01-01

The US Environmental Protection Agency (USEPA) is reviewing the protectiveness of the national ambient water quality criteria (WQC) for aluminum (Al) and compiling a toxicity data set to update the WQC. Freshwater mussels are one of the most imperiled groups of animals in the world, but little is known about their sensitivity to Al. The objective of the present study was to evaluate acute 96‐h and chronic 28‐d toxicity of Al to a unionid mussel (Lampsilis siliquoidea) and a commonly tested amphipod (Hyalella azteca) at a pH of 6 and water hardness of 100 mg/L as CaCO3. The acute 50% effect concentration (EC50) for survival of both species was >6200 μg total Al/L. The EC50 was greater than all acute values in the USEPA acute Al data set for freshwater species at a pH range of 5.0 to <6.5 and hardness normalized to 100 mg/L, indicating that the mussel and amphipod were insensitive to Al in acute exposures. The chronic 20% effect concentration (EC20) based on dry weight was 163 μg total Al/L for the mussel and 409 μg total Al/L for the amphipod. Addition of the EC20s to the USEPA chronic Al data set for pH 5.0 to <6.5 would rank the mussel (L. siliquoidea) as the fourth most sensitive species and the amphipod (H. azteca) as the fifth most sensitive species, indicating the 2 species were sensitive to Al in chronic exposures. The USEPA‐proposed acute and chronic WQC for Al would adequately protect the mussel and amphipod tested; however, inclusion of the chronic data from the present study and recalculation of the chronic criterion would likely lower the proposed chronic criterion. 

Petroleum hydrocarbon toxicity to corals: A review.

Science.gov (United States)

Turner, Nicholas R; Renegar, D Abigail

2017-06-30

The proximity of coral reefs to coastal urban areas and shipping lanes predisposes corals to petroleum pollution from multiple sources. Previous research has evaluated petroleum toxicity to coral using a variety of methodology, including monitoring effects of acute and chronic spills, in situ exposures, and ex situ exposures with both adult and larval stage corals. Variability in toxicant, bioassay conditions, species and other methodological disparities between studies prevents comprehensive conclusions regarding the toxicity of hydrocarbons to corals. Following standardized protocols and quantifying the concentration and composition of toxicant will aid in comparison of results between studies and extrapolation to actual spills. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2017-06-01

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

[Behavioral-cognitive disorders due to chronic exposure to industrial and environmental toxic substances].

Science.gov (United States)

Mangone, Carlos A; Genovese, Osvaldo; Abel, Carlos

2006-01-01

A review of neurotoxics is made, given the low tendency to investigate for chronic exposure to environmental and industrial potential central nervous system toxic substances (heavy metals, insecticides, organic solvents and carbon monoxide) in the history of a patient consulting for behavioral - cognitive complains, and considering the potential overturn of the disease if a correct diagnosis and early treatment is made. to determine the onset of the cognitive - behavioral features, presentation pattern, diagnosis and treatment of such neurotoxics (NT). systematized search in Cochrane and Medline reviews, Embase and Lilacs. chronic exposure to neurotoxics can produce personality changes (sleeping problems, excitation, depression, delusions and hallucinations) as well as cognitive problems (memory, learning, language and cognitive reaction problems). NT may cause changes in the neuron morphology and its sub cellular structures, affecting its normal biochemistry and physiology (proteins and neurotransmitters synthesis). The clinical history, diagnosis and treatment of each neurotoxic are discussed. The NT must be taken in consideration among the possible different etiologies when a patient with a bizarre behavioral cognitive syndrome is examined.

Progress in the development of short term chronic toxicity testing methods for crude oil and commercial bioremediation agents

International Nuclear Information System (INIS)

Cavender, R.C.; Cherry, D.S.; Dobbs, M.G.; Bidwell, J.R.; Yeager, M.M.

1995-01-01

Proposed modifications to the National Oil and Hazardous Substance Pollution Contingency Plan (NCP) have prompted examinations of the methodology used in toxicity testing of the water soluble fraction of oil, commercial bioremediation agents (CBA), and a combination of the two. The specific concerns addressed by this research are the use of unweathered Alaska North Slope (ANS) crude oil instead of the more expensive, less environmentally realistic distillate ANS-521, and the appropriate laboratory preparation methodology for the water soluble fraction (WSF) used in testing. Seven-day chronic tests exposing the inland silverside (Menidia beryllina) and estuarine mysid (Mysidopsis bahia) to the water soluble fraction of unweathered ANS and ANS-521 showed that mysids responded similarly to the two types of oils while silversides were more sensitive to unweathered ANS. In the presence of a CBA and WSF, the mortality of the organisms and the mysid growth were similar in both types of oil. The NOEC for silverside growth, however, was lower in the combined exposure of a CBA with ANS-521 WSF than it was in the CBA-WSF unweathered ANS. Testing is underway to determine if the stirring time length effects the toxicity of the WSF, or the WSF and CBA combination. In chronic tests using both the silverside and mysid there were no differences in growth and mortality of the organisms tested in WSF prepared from 10 and 20 hours of stirring, however, the 5 hour stirring exposure is less toxic to both organisms

Intensity-Modulated Radiotherapy Results in Significant Decrease in Clinical Toxicities Compared With Conventional Wedge-Based Breast Radiotherapy

International Nuclear Information System (INIS)

Harsolia, Asif; Kestin, Larry; Grills, Inga; Wallace, Michelle; Jolly, Shruti; Jones, Cortney; Lala, Moinaktar; Martinez, Alvaro; Schell, Scott; Vicini, Frank A.

2007-01-01

Purpose: We have previously demonstrated that intensity-modulated radiotherapy (IMRT) with a static multileaf collimator process results in a more homogenous dose distribution compared with conventional wedge-based whole breast irradiation (WBI). In the present analysis, we reviewed the acute and chronic toxicity of this IMRT approach compared with conventional wedge-based treatment. Methods and Materials: A total of 172 patients with Stage 0-IIB breast cancer were treated with lumpectomy followed by WBI. All patients underwent treatment planning computed tomography and received WBI (median dose, 45 Gy) followed by a boost to 61 Gy. Of the 172 patients, 93 (54%) were treated with IMRT, and the 79 patients (46%) treated with wedge-based RT in a consecutive fashion immediately before this cohort served as the control group. The median follow-up was 4.7 years. Results: A significant reduction in acute Grade 2 or worse dermatitis, edema, and hyperpigmentation was seen with IMRT compared with wedges. A trend was found toward reduced acute Grade 3 or greater dermatitis (6% vs. 1%, p = 0.09) in favor of IMRT. Chronic Grade 2 or worse breast edema was significantly reduced with IMRT compared with conventional wedges. No difference was found in cosmesis scores between the two groups. In patients with larger breasts (≥1,600 cm 3 , n = 64), IMRT resulted in reduced acute (Grade 2 or greater) breast edema (0% vs. 36%, p <0.001) and hyperpigmentation (3% vs. 41%, p 0.001) and chronic (Grade 2 or greater) long-term edema (3% vs. 30%, p 0.007). Conclusion: The use of IMRT in the treatment of the whole breast results in a significant decrease in acute dermatitis, edema, and hyperpigmentation and a reduction in the development of chronic breast edema compared with conventional wedge-based RT

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

Science.gov (United States)

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

2011-09-01

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

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

Science.gov (United States)

Kristanc, Luka; Kreft, Samo

2016-06-01

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

Remarkable Presentation: Anaplastic Thyroid Carcinoma Arising from Chronic Hyperthyroidism

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Habib G. Zalzal

2018-01-01

Full Text Available Background. Undifferentiated anaplastic carcinoma rarely develops from chronic hyperthyroidism. Although acute hyperthyroidism can develop prior to anaplastic transformation, chronic hyperthyroidism was thought to be a protective measure against thyroid malignancy. Methods. A 79-year-old female presented acutely to the hospital with dyspnea. She had been taking methimazole for chronic hyperthyroidism due to toxic thyroid nodules, previously biopsied as benign. Upon admission, imaging showed tracheal compression, requiring a total thyroidectomy with tracheostomy for airway management. Results. Pathology demonstrated undifferentiated anaplastic thyroid carcinoma. The patient passed away shortly after hospital discharge. Despite treatment with methimazole for many years, abrupt enlargement of her toxic multinodular goiter was consistent with malignant transformation. Chronic hyperthyroidism and toxic nodules are rarely associated with thyroid malignancy, with only one previous report documenting association with anaplastic thyroid carcinoma. Conclusion. Progressive thyroid enlargement and acute worsening of previously controlled hyperthyroidism should promote concern for disease regardless of baseline thyroid function.

Possible potassium chlorate nephrotoxicity associated with chronic matchstick ingestion*

OpenAIRE

Thurlow, John S.; Little, Dustin J.; Baker, Thomas P.; Yuan, Christina M.

2013-01-01

We present a case of a 48-year-old active duty male soldier with a history of chronic exposure to potassium chlorate, later diagnosed with chronic interstitial nephritis. He reported regular matchstick consumption to prevent chigger (Trombicula autumnalis) bites, amounting to ?5.8 g of potassium chlorate over 3 years. Potassium chlorate can cause anuric renal failure within days of a toxic dose. Its slow excretion and mechanism of action suggest that renal toxicity may result from lower-dose ...

Role of oxidative stress in liver and kidney in uranium toxicity after chronic exposure

International Nuclear Information System (INIS)

Poisson - Moreau-De-Lizoreux, C.

2013-01-01

Uranium is a radioactive heavy metal found in the environment. Due to its natural presence and to civil and militaries activities, general population can be exposed to U throughout drinking water or contaminated food. The pro/anti-oxidative system is a defense system which is often implicated in case of acute exposure to U. The aim of this thesis is to study the role of the pro/anti-oxidative system after chronic exposure to U in the liver and the kidney. After chronic exposure of rats to different U concentrations, this radionuclide accumulated in the organs in proportion to U intake; until 6 μg.g -1 of kidney tissues. U is localized in nucleus of the proximal tubular cells of the kidney. No nephrotoxicity was described even for the higher U level in drinking water and a reinforcement of the pro/anti-oxidative system with an increase in glutathione is observed. The study of U internal contamination in Nrf2 deficient mice, a cytoprotective transcription factor involved in the anti-oxidative defense has been realized. U accumulate more in Nrf2 mice than in WT mice but the biologic effects of U on the pro/anti-oxidative system did not seem to implicate Nrf2. At the cell level, a correlation between U distribution in HepG2 cells and the biological effects on this system is observed after U exposure at low concentrations. Soluble distribution of U is observed in cell nucleus. The apparition of U precipitates is correlated to the establishment of the adaptive mechanisms overtime which are overwhelmed and lead to a cellular toxicity at higher U level. In conclusion, these results suggest that the reinforcement of pro/anti-oxidative system could be an adaptive mechanism after chronic exposure at low U concentration. (author) [fr

Waste Load Allocation for Whole Effluent Toxicity to Protect Aquatic Organisms

Science.gov (United States)

Hutcheson, M. R.

1992-11-01

A process is developed to determine a waste load allocation that will implement the narrative criteria for fish and wildlife propagation found in states' water quality standards. The waste load allocation to implement the narrative chronic criterion is determined to be percent effluent at a location in the receiving stream, as opposed to an effluent concentration derived from the numerical waste load allocation process. A typical narrative chronic criterion is "receiving streams shall not exhibit chronic toxicity outside the mixing zone," while a typical numerical chronic criterion is "receiving stream concentration shall not exceed 0.005 μg/L of chlordane outside the mixing zone." Toxicity tests are used to implement narrative criteria, while compliance with numerical criteria involves concentration measurements. It is shown that the appropriate percent effluent is inversely proportional to the dilution factor for chronic toxicity. An appropriate waste load allocation to implement the narrative acute criterion is 100% effluent. Waste load allocation for whole effluent toxicity is feasible. The required independent variables are available to regulatory agencies, and toxicity testing has become routine.

FEEDING OF FERRETS WITH THE RAW MEAT AND LIVER OF CHICKENS CHRONICALLY POISONED WITH TOXIC GROUNDNUT MEAL.

Science.gov (United States)

PLATONOW, N; BEAUREGARD, M

1965-03-01

Chickens were fed a ration containing 30 per cent of toxic groundnut meal for up to six weeks. The concentration of aflatoxin (toxic metabolites of Aspergillus flavus) in the above ration was 3.06 p.p.m. At the end of 2nd, 4th or 6th week the birds were killed. The meat was removed from the bones and put through a meat grinder. The livers of three groups were pooled together. Three control groups of birds kept on commercial pellets were treated similarly. Female ferrets, two years of age, were used in the present study. They were divided into four groups. The first three groups were given for one month meat from chickens fed the toxic ration for 2, 4, and 6 weeks, respectively. Each of these three groups contained one control ferret that was fed with the meat of chickens fed a commercial ration for a similar period of time. One half of the 4th group was fed pooled liver from intoxicated birds and one half was fed liver from control birds. No significant changes in the ferret tissues were observed as a consequence of feeding them with the meat or liver from the chickens chronically poisoned with toxic groundnut meal.

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

Science.gov (United States)

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. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Chronic toxicity risk after radiotherapy for patients with systemic sclerosis (systemic scleroderma) or systemic lupus erythematosus: Association with connective tissue disorder severity

International Nuclear Information System (INIS)

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

2008-01-01

No method reliably identifies which patients with connective tissue disorders are at greatest risk of radiotherapy-related complications. Building on our prior experience, we postulated that disease severity, as measured by the number of organ systems involved, may predict chronic radiation toxicity risk

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

Science.gov (United States)

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

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

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Xiaoxia Gao

2018-01-01

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

Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

International Nuclear Information System (INIS)

Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

2007-01-01

Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

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

Science.gov (United States)

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

2017-10-01

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

Acute and chronic arsenic toxicity

OpenAIRE

Ratnaike, R

2003-01-01

Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption o...

Toxicity evaluation of 2-hydroxybiphenyl and other compounds involved in studies of fossil fuels biodesulphurisation.

Science.gov (United States)

Alves, L; Paixão, S M

2011-10-01

The acute toxicity of some compounds used in fossil fuels biodesulphurisation studies, on the respiration activity, was evaluated by Gordonia alkanivorans and Rhodococcus erythropolis. Moreover, the effect of 2-hydroxybiphenyl on cell growth of both strains was also determined, using batch (chronic bioassays) and continuous cultures. The IC₅₀ values obtained showed the toxicity of all the compounds tested to both strains, specially the high toxicity of 2-HBP. These results were confirmed by the chronic toxicity data. The toxicity data sets highlight for a higher sensitivity to the toxicant by the strain presenting a lower growth rate, due to a lower cells number in contact with the toxicant. Thus, microorganisms exhibiting faster generation times could be more resistant to 2-HBP accumulation during a BDS process. The physiological response of both strains to 2-HBP pulse in a steady-state continuous culture shows their potential to be used in a future fossil fuel BDS process. Copyright © 2011 Elsevier Ltd. All rights reserved.

LEVEL OF TOXICITY WATER AREA «TULENIY» AS A RESULT OF BIOASSAY

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A. F. Sokolsky

2014-01-01

Full Text Available Aim. To determine the toxicity of marine waters area " tuleniy ".Location. Area " tuleniy ".Methods. Determining the level of toxicity of marine waters area "seal" method for biological testing was conducted according tothe guidelines approved by the Ministry of natural resources (guidance on the definition of ..., 2002; Dolzhenko, 1978. Guide prepared by the Center for Russian register of hydraulic structures and the state water cadastre of the MNR of Russia jointly with specialists of the Institute Committee of Russia and the UNION of ecological problems of the Ministry of Ukraine. The basis of the proposed system of marine toxicity biotests based on the results of generalization of experimental research based on the problem of pollution of water bodies and numerous literature data, making it possible to identify features of the response of aquatic organisms of different taxonomic groups to toxic impurities of different nature and origin. Experimental studies were conducted on the culture of marine unicellular algae Phaeodactylum tricornutum on planktonic crustacea Acartia tonsa, the larvae of the chironomid Chironomus gr.salinarius and juvenile guppies Poecillia reticulata Peters.Results. Comparative analysis of the results of research from 2001 to 2006 showed no acute toxic effect on the test object zooplankton and phytoplanton.Main conclusions. Throughout the study period (2001-2003, 2005-2006, you must allocate the spring of 2002, when it was recorded,the average of the lowest five years of research, the level of toxicity of water for the analyzed area.Considering the results of biological testing of the surveyed area by periods, it should be noted that the average level of toxicity of the waters did not undergo significant changes and were on the same level, not exceeding 17,6% (table. 1. According to the classification shown in table 2, the water in the surveyed area is assessed as "non-toxic".

Wild lettuce (Lactuca virosa) toxicity

OpenAIRE

Besharat, Sima; Besharat, Mahsa; Jabbari, Ali

2009-01-01

Wild lettuce (Lactuca virosa) can cause toxic effects when eaten. Wild lettuce grows in the north of Iran and some natives consume it unaware of its adverse side effects. We describe eight patients with manifestations of wild lettuce toxicity, admitted to a general hospital affiliated to the Golestan University of Medical Sciences. All the patients recovered (although one had to spend 48 h in the intensive care unit) and no chronic complications were reported. A clinical suspicion of toxicity...

Toxicities of sediments below 10 effluent outfalls to near-coastal areas of the Gulf of Mexico

International Nuclear Information System (INIS)

Lewis, M.; Weber, D.; Stanley, R.

1995-01-01

The chemical quality and toxicities of sediments collected in the receiving waters below 10 wastewater outfalls to Northwest Florida coastal areas were evaluated at multiple stations during 1994--1996. Eight types of toxicity tests using 11 test species were used to assess acute and chronic toxicity of the sediments collected below industrial, municipal, power generation and pulp mill outfalls. The primary objectives of the study were to evaluate the relative ability of different assessment procedures to detect toxicity and to provide some much-needed perspective on the impact of major point sources on sediment quality in Gulf of Mexico estuaries. The major chemical contaminants were heavy metals and PAHs. Acute and chronic toxicities were noted. Results of tests with sediment collected at the same location but several months later often differed. The most sensitive species were mysids and an estuarine amphipod. The least sensitive species were fish and macrophyte seedlings. There was poor correlation of effluent toxicity to sediment toxicity in the receiving water. Toxicity of the effluents was greater than that of the sediments. Overall, the unavailability of relevant chronic toxicity methods, uncertain criteria for choice of control stations, lack of guidance on frequency of testing and the dynamic physical and chemical characteristics of sediments are factors that need consideration if sediment monitoring is to be part of the NPDES regulatory process

In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

Science.gov (United States)

Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

2018-04-15

The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

Summary of safety evaluation toxicity studies of glufosinate ammonium.

Science.gov (United States)

Ebert, E; Leist, K H; Mayer, D

1990-05-01

This article reviews the results of toxicity studies to evaluate the safety of the herbicide glufosinate ammonium (GLA) and its formulation (200 g/litre) in laboratory animals. The data show that GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced GLA and its formulation are slightly toxic following oral exposure. In addition, the formulation induced slight dermal toxicity and eye irritation. Testing for teratogenicity in rats and rabbits indicated no teratogenic potential, and numerous mutagenicity tests showed GLA to be non-genotoxic. Chronic toxicity testing in rats and dogs yielded no-observable-effect levels of 2 and 5 mg/kg body weight/day, respectively. Oncogenicity studies in rats and mice revealed no carcinogenic potential. On the basis of these toxicity data it is concluded that this herbicide is safe under conditions of recommended use.

Effects in Plant Populations Resulting from Chronic Radiation Exposure

Energy Technology Data Exchange (ETDEWEB)

Geras' kin, Stanislav A.; Volkova, Polina Yu.; Vasiliyev, Denis V.; Dikareva, Nina S.; Oudalova, Alla A. [Russian Institute of Agricultural Radiology and Agroecology, 249032, Obninsk (Russian Federation)

2014-07-01

Human industrial activities have left behind a legacy of ecosystems strongly impacted by a wide range of contaminants, including radionuclides. Phyto-toxic effects of acute impact are well known, but the consequences of long-term chronic exposure to low pollutant concentrations is neither well understood nor adequately included in risk assessments. To understand effects of real-world contaminant exposure properly we must pay attention to what is actually going on in the field. However, for many wildlife groups and endpoints, there are no, or very few, studies that link accumulation, chronic exposure and biological effects in natural settings. To fill the gaps, results of field studies carried out on different plant species (winter rye and wheat, spring barley, oats, Scots pine, wild vetch, crested hair-grass) in various radioecological situations (nuclear weapon testing, the Chernobyl accident, uranium and radium processing) to investigate effects of long-term chronic exposure to radionuclides are discussed. Because each impacted site developed in its own way due to a unique history of events, the experience from one case study is rarely directly applicable to another situation. In spite of high heterogeneity in response, we have detected several general patterns. Plant populations growing in areas with relatively low levels of pollution are characterized by the increased level of both cytogenetic alterations and genetic diversity. Accumulation of cellular alterations may afterward influence biological parameters important for populations such as health and reproduction. Presented data provide evidence that in plant populations inhabiting heavily contaminated territories cytogenetic damage were accompanied by decrease in reproductive ability. In less contaminated sites, because of the scarcity of data available, it is impossible to establish exactly the relationship between cytogenetic effects and reproductive ability. Radioactive contamination of the plants

Experimental evaluation of toxicity of selected mixtures used in metallurgy

Energy Technology Data Exchange (ETDEWEB)

Drozdz, M; Stawiarska, B; Kucharz, E; Glowacki, A; Janecki, M; Grucka-Mamczar, E; Olczyk, K; Piwowarczyk, B

1982-01-01

The investigation is aimed at evaluation of the effects of copper-coating and bonderizing solutions and oil--emulsion used in technological processes in the metallurgic industry upon hematological and biochemical changes in rats' peripheral blood. The studies were performed on male Wistar rats. The solutions were carried onto hairy and depilated skin. Acute toxicity was evaluated in two-weeks' experiment and chronic toxicity in three--months' experiment. The copper-coating solution was found to be most hazardous, whereas the oil emulsion-the least hazardous. The copper-coating and bonderizing solutions, when chronically applied, result in anaemia and changes in the percentage picture of leucocytes, and also increased blood concentration of uric acid, creatinine and hydroxyproline. No significant changes in concentrations of the remaining biochemical indices were found. The results point to synergistic effects of oil-emulsion and copper-coating solution.

Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.

Science.gov (United States)

Song, Taeksun; Lee, Myungsun; Jeon, Han-Seung; Park, Yumi; Dodd, Lori E; Dartois, Véronique; Follman, Dean; Wang, Jing; Cai, Ying; Goldfeder, Lisa C; Olivier, Kenneth N; Xie, Yingda; Via, Laura E; Cho, Sang Nae; Barry, Clifton E; Chen, Ray Y

2015-11-01

Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23-7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-08-30

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

Vitamin D, Essential Minerals, and Toxic Elements: Exploring Interactions between Nutrients and Toxicants in Clinical Medicine

Science.gov (United States)

Schwalfenberg, Gerry K.; Genuis, Stephen J.

2015-01-01

In clinical medicine, increasing attention is being directed towards the important areas of nutritional biochemistry and toxicant bioaccumulation as they relate to human health and chronic disease. Optimal nutritional status, including healthy levels of vitamin D and essential minerals, is requisite for proper physiological function; conversely, accrual of toxic elements has the potential to impair normal physiology. It is evident that vitamin D intake can facilitate the absorption and assimilation of essential inorganic elements (such as calcium, magnesium, copper, zinc, iron, and selenium) but also the uptake of toxic elements (such as lead, arsenic, aluminum, cobalt, and strontium). Furthermore, sufficiency of essential minerals appears to resist the uptake of toxic metals. This paper explores the literature to determine a suitable clinical approach with regard to vitamin D and essential mineral intake to achieve optimal biological function and to avoid harm in order to prevent and overcome illness. It appears preferable to secure essential mineral status in conjunction with adequate vitamin D, as intake of vitamin D in the absence of mineral sufficiency may result in facilitation of toxic element absorption with potential adverse clinical outcomes. PMID:26347061

[Nutritional components and sub-chronic toxicity of genetically modified rice expressing human lactoferrin].

Science.gov (United States)

Hu, Yichun; Piao, Jianhua; Yang, Xiaoguang

2012-01-01

To compare the nutritional components of genetically modified rice expressing human lactoferrin (hLf) with its parental rice, and to observe the sub-chronic toxicity of hLf rice. The nutritional components of hLf rice and its parental rice were determined by the National Standard Methods. Eighty weanling Wistar rats were randomly divided into 4 groups based on their gender and body weight: group A (hLf rice high-dose group with 71.45% rice), group B (hLf rice medium-dose group with 35. 725% rice), group C (parental rice group with 71.01% rice) and group D (AIN-93G diet group), and the latter two groups were used as the control. Body weight, dietary intake, blood routine test, blood biochemical examination, organ coefficient, bone density and the pathology of organs were investigated at the end of a 90-day feeding experiment. Except for human lactoferrin and Fe, there was no difference of main nutritional components, minerals and vitamins between groups. The differences of some indicators of blood routine (WBC, HGB, RBC and MCH), blood biochemistry (AST and GLU), organ coefficient and bone density between group A and B (hLf rice) with group C (parental rice) or group D (AIN-93G) were significant, while no difference of other indicators. Although some differences were observed, all indicators were still in the normal reference range. Therefore, there was no sign of toxic and adverse effects for hLf rice on rats.

Identification of manganese as a toxicant in a groundwater treatment system: Addressing naturally occurring toxicants

International Nuclear Information System (INIS)

Goodfellow, W. Jr.; Sohn, V.; Richey, M.; Yost, J.

1995-01-01

Effluent from a groundwater remediation system at a bulk oil storage and distribution terminal has been chronically toxic to Ceriodaphnia dubia. The remediation system was designed in response to a hydrocarbon plume in the area of the terminal. The remediation system consists of a series of groundwater recovery wells and groundwater intercept trench systems with groundwater treatment and phased-separated hydrocarbon recovery systems. The groundwater treatment and petroleum recovery systems consist of oil/water separators, product recovery tanks, air strippers, filters, and carbon adsorption units. The characteristics of this effluent are low total suspended solids, total dissolved solids, and hardness concentrations as well as meeting stringent NPDES permit requirements for lead, copper, zinc, mercury, total petroleum hydrocarbons, and BTEX. Additional priority pollutant evaluations revealed no compounds of concern. Performance of a Toxicity identification Evaluation (TIE) indicated that manganese was the principle toxicant in the effluent. Manganese is a naturally occurring constituent in this groundwater source and is not added to the treatment system. This paper will present the results of the TIE with a discussion of treatability/control options for manganese control at this facility. Recommendations for addressing naturally occurring toxicants that are not a result of the facility's operations will also be presented

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

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Godwin Sokpor

2012-05-01

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

Toxicity identification evaluation of cosmetics industry wastewater.

Science.gov (United States)

de Melo, Elisa Dias; Mounteer, Ann H; Leão, Lucas Henrique de Souza; Bahia, Renata Cibele Barros; Campos, Izabella Maria Ferreira

2013-01-15

The cosmetics industry has shown steady growth in many developing countries over the past several years, yet little research exists on toxicity of wastewaters it generates. This study describes a toxicity identification evaluation conducted on wastewater from a small Brazilian hair care products manufacturing plant. Physicochemical and ecotoxicological analyses of three wastewater treatment plant inlet and outlet samples collected over a six month period revealed inefficient operation of the treatment system and thus treated wastewater organic matter, suspended solids and surfactants contents consistently exceeded discharge limits. Treated wastewater also presented high acute toxicity to Daphnia similis and chronic toxicity to Ceriodaphnia dubia and Pseudokirchneriella subcapitata. This toxicity was associated with suspended solids, volatile or sublatable and non-polar to moderately polar organic compounds that could be recovered in filtration and aeration residues. Seven surfactants used in the largest quantities in the production process were highly toxic to P. subcapitata and D. similis. These results indicated that surfactants, important production raw materials, are a probable source of toxicity, although other possible sources, such as fragrances, should not be discarded. Improved treatment plant operational control may reduce toxicity and lower impact of wastewater discharge to receiving waters. Copyright © 2012 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

Neurological manifestation of phenytoin toxicity, resulting from drug ...

African Journals Online (AJOL)

Phenytoin toxicity masquerading as deterioration of neurological symptoms caused by interaction with chloramphenicol is a very rare but real risk. To the authors' knowledge only one such case occurring in humans has been reported in the English literature. No case of clinical phenytoin toxicity occurring at less than ...

Toxicity of Depleted Uranium Dust Particles: Results of a New Model

International Nuclear Information System (INIS)

Zucchetti, M.

2013-01-01

Depleted uranium (DU) is mostly composed of U-238, a naturally radioactive isotope. Concerning chemical toxicity, uranium, being a heavy metal, is known to have toxic effects on specific organs in the body, the kidneys in particular. Its effects are similar to those of other heavy metals, such as lead and cadmium. Scientific evidence resulting both from in vitro and in vivo analyses shows that current models of the mechanisms of toxicity of uranium dust are not fully satisfactory. They should be refined in order to obtain more effective responses and predictions regarding health effects. In particular, radiotoxicity potential of Depleted Uranium dust originated by military use of this material for ammunition must be re-evaluated taking into account the bystander effect, the dose enhancing effect and other minor phenomena. Uranium dust has both chemical and radiological toxicity: the synergistic aspect of the two effects has to be accounted for, in order to arrive to a complete description of the phenomenon. The combination of the two different toxicities (chemical and radiological) of depleted uranium is attempted here for the first time, approaching the long-term effects of Depleted Uranium, and in particular the carcinogenetic effects. A case study (Balkan war, 1999) is discussed. (Author)

Evaluation of cytotoxic effects and acute and chronic toxicity of aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) in rodents.

Science.gov (United States)

Lyoussi, Badiaa; Cherkaoui Tangi, Khadija; Morel, Nicole; Haddad, Mohamed; Quetin-Leclercq, Joelle

2018-01-01

The present investigation was carried out to evaluate the safety of an aqueous extract of the seeds of Calycotome villosa (Poiret) Link (subsp. intermedia) by determining its cytotoxicity and potential toxicity after acute and sub-chronic administration in rodents. Cytotoxic activity was tested in cancer and non-cancer cell lines HeLa, Mel-5, HL-60 and 3T3. Acute toxicity tests were carried out in mice by a single oral administration of Calycotome seed-extract (0 - 12 g/kg) as well as intraperitoneal doses of 0 - 5 g/kg. Sub-chronic studies were conducted in Wistar rats by administration of oral daily doses for up to 90 days. Changes in body and vital organ weights, mortality, haematology, clinical biochemistry and histologic morphology were evaluated. The lyophilized aqueous extract of C. villosa exhibited a low cytotoxicity in all cell lines tested with an IC 50 > 100 µg/ml. In the acute study in mice, intra-peritoneal administration caused dose-dependent adverse effects and mortality with an LD 50 of 4.06 ± 0.01 g/kg. In the chronic tests, neither mortality nor visible signs of lethality was seen in rats. Even AST and ALT were not affected while a significant decrease in serum glucose levels, at 300 and 600 mg/kg was detected. Histopathological examination of the kidney and liver did not show any alteration or inflammation at the end of treatment. In conclusion, the aqueous extract of C. villosa seed appeared to be non-toxic and did not produce mortality or clinically significant changes in the haematological and biochemical parameters in rats.

The use of drug-free technologies in patients with chronic toxicochemical bronchitis

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Illarionov V.E.

2014-12-01

Full Text Available Aim: development and scientific substantiation of a complex application halo-inhaled and flutter-kinesiotherapy in patients with chronic obstructive toxic chemical bronchitis. Material and methods. There was an examination and treatment of 125 patients with chronic obstructive toxic chemical bronchitis at the age from 32 to 65 years (average age 52.2+3,1 with industrial experience from 5 to 27 years (average age 15.9+3,9. Results. Comparative analysis revealed an advantage of an integrated application halo-inhaled and flutter-kinesiotherapy in patients with chronic obstructive toxic chemical bronchitis as in the I, and that is especially important at the II stage of the disease, which is confirmed by the regression of the main clinical symptoms, a significant decrease in the intensity index of inflammation, recovery to normal values of factors of local immunity broncho-pulmonary system. Conclusion. Developed a comprehensive program including halo-inhaled and flutter-kinesiotherapy in patients with chronic obstructive toxic chemical bronchitis has a pronounced anti-inflammatory, antibacterial and immunocorrection effect, improves bronchodilating function and bronchial obstruction in bronchial tubes of large, medium and small caliber. The absence of exacerbations in the past year proves that this method is highly effective secondary prevention of lung disease.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-10-15

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

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

International Nuclear Information System (INIS)

De Schamphelaere, K.A.C.; Stubblefield, W.; Rodriguez, P.; Vleminckx, K.; Janssen, C.R.

2010-01-01

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

Vascular toxicity of urea, a new "old player" in the pathogenesis of chronic renal failure induced cardiovascular diseases.

Science.gov (United States)

Giardino, Ida; D'Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-12-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure.

Hematopoiesis under conditions of chronic toxicity

International Nuclear Information System (INIS)

Seed, T.M.; Kaspar, L.V.

1985-01-01

The objective of this project is to elucidate the cellular processes by which chronic exposure to low daily doses of ionizing radiation induce and promote the development of either aplastic anemia or myeloid leukemia, i.e., two prominent pathological consequences of radiation exposure. 5 refs

Curcumin mitigates fenthion-induced testicular toxicity in rats ...

African Journals Online (AJOL)

Fenthion is a widely used organophosphorus pesticide in agriculture that induces different cytotoxic effects, including male reproductive toxicity. The present work aimed to study the ameliorative effects of curcumin, a potential therapeutic agent against several chronic diseases, on reproductive toxicity induced by the ...

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

Science.gov (United States)

Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

2013-01-01

The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

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Bryan L. Stegelmeier

2016-11-01

Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

The Toxicity of Depleted Uranium

OpenAIRE

Briner, Wayne

2010-01-01

Depleted uranium (DU) is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a c...

Toxicity studies of the water extract from the calyces of Hibiscus sabdariffa L. in rats.

Science.gov (United States)

Sireeratawong, Seewaboon; Itharat, Arunporn; Khonsung, Parirat; Lertprasertsuke, Nirush; Jaijoy, Kanjana

2013-01-01

Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and differences of the weights or behaviour compared to the control rats were observed. The results indicated that the single oral administration of H. sabdariffa extract in the amount of 5,000 mg/kg body weight does not produce acute toxicity. The chronic toxicity was determined by oral feeding both male and female rats daily with the extract at the doses of 50, 100, and 200 mg/kg body weight for 270 days. The examinations of signs, animal behaviour and health monitoring showed no defects in the test groups compared to the control groups. Both test and control groups (day 270th) and satellite group (day 298th) were analysed by measuring their final body and organ weights, taking necropsy, and examining haematology, blood clinical chemistry, and microanatomy. Results showed no differences from the control groups. Overall, our study demonstrated that an oral administration of H. sabdariffa extract at the doses of 50, 100 and 200 mg/kg body weight for 270 days does not cause chronic toxicity in rat.

[Morphology and pathogenesis of visceral manifestations of chronic alcoholism].

Science.gov (United States)

Lebedev, S P

1982-01-01

Chronic alcoholism is accompanied by systemic involvement of the internal organs. Clinico-morphological forms of chronic alcoholism are distinguished on the basis of the prevailing organ pathology, Morphological data are presented, and pathogenesis of the lesions of the liver, heart, pancreas, and kidneys in patients with chronic alcoholism is analysed. The hepatic form may present alcoholic dystrophy, hepatitis or cirrhosis which are stages of progressing hepatopathy. The toxic and metabolic effect of ethanol is important in the pathogenesis of liver lesion. The cardiac form is characterized by the development of alcoholic myocardiodystrophy. In addition to the toxic influence of ethanol, hormonal and electrolyte changes and microcirculatory disorders play a role in its pathogenesis. Chronic calcifying pancreatitis in chronic alcoholism is associated with the effect of ethanol on the mediatory system. The renal form any present necronephrosis, hepatorenal syndrome, glomerulonephritis or pyelonephritis. Their pathogenesis is determined by toxicity of ethanol, circulation of immune complexes in the blood, or immunosuppression.

Chronic toxicity of sediment-associated linear alkylbenzene sulphonates (LAS) to freshwater benthic organisms

Energy Technology Data Exchange (ETDEWEB)

Comber, S.D.W. [WRc-NSF, Henley Road, Medmenham, Marlow, Buckinghamshire, SL7 2HD (United Kingdom)]. E-mail: sean.comber@atkinsglobal.com; Conrad, A.U. [Weinberg Group, Blue Tower, Box 16, B-1050 Brussels (Belgium); Hoess, S. [ECOSSA, Thierschstrasser 43, 80538, Muenchen (Germany); Webb, S. [CEFIC, Ave E. Van Nieuwenhuyse 4, B-1160 Brussels (Belgium); Marshall, S. [Unilever Research, Environment Centre, Bebington, Wirral, Merseyside, L63 3JW (United Kingdom)

2006-11-15

The toxicity of linear alkylbenzene sulphonates (LAS), to freshwater benthic organisms was assessed during exposure to spiked sediment. Lethal and sub-lethal end-points were monitored for two organisms (oligochaete Lumbriculus variegatus and nematode Caenorhabditis elegans). Results demonstrated relatively low toxicity (LOECs >100 mg/kg dry weight). No observed effect concentrations (NOECs) of 81 mg/kg dw (Lumbriculus) and 100 mg/kg dw (Caenorhabditis) were determined. For the oligochaete, no specific endpoint was particularly sensitive to LAS. For the nematode, egg production was the most sensitive endpoint. Significant degradation was measured over the 28-day duration of the Lumbriculus study, equating to a half-life of 20 days in sediment. - This paper provides sediment toxicity data for LAS, essential for a detailed and accurate environment risk assessment.

Chronic toxicity of sediment-associated linear alkylbenzene sulphonates (LAS) to freshwater benthic organisms

International Nuclear Information System (INIS)

Comber, S.D.W.; Conrad, A.U.; Hoess, S.; Webb, S.; Marshall, S.

2006-01-01

The toxicity of linear alkylbenzene sulphonates (LAS), to freshwater benthic organisms was assessed during exposure to spiked sediment. Lethal and sub-lethal end-points were monitored for two organisms (oligochaete Lumbriculus variegatus and nematode Caenorhabditis elegans). Results demonstrated relatively low toxicity (LOECs >100 mg/kg dry weight). No observed effect concentrations (NOECs) of 81 mg/kg dw (Lumbriculus) and 100 mg/kg dw (Caenorhabditis) were determined. For the oligochaete, no specific endpoint was particularly sensitive to LAS. For the nematode, egg production was the most sensitive endpoint. Significant degradation was measured over the 28-day duration of the Lumbriculus study, equating to a half-life of 20 days in sediment. - This paper provides sediment toxicity data for LAS, essential for a detailed and accurate environment risk assessment

Assessment of Pharmacogenomic Panel Assay for Prediction of Taxane Toxicities: Preliminary Results

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Raffaele Di Francia

2017-11-01

Full Text Available Backbone: Paclitaxel and docetaxel are the primary taxane anticancer drugs regularly used to treat, breast, gastric, ovarian, head/neck, lung, and genitourinary neoplasm. Suspension of taxane treatments compromising patient benefits is more frequently caused by peripheral neuropathy and allergy, than to tumor progression. Several strategies for preventing toxicity have been investigated so far. Recently, findings on the genetic variants associated with toxicity and resistance to taxane-based chemotherapy have been reported.Methods: An extensive panel of five polymorphisms on four candidate genes (ABCB1, CYP2C8*3, CYP3A4*1B, XRCC3, previously validated as significant markers related to paclitaxel and Docetaxel toxicity, are analyzed and discussed. We genotyped 76 cancer patients, and 35 of them received paclitaxel or docetaxel-based therapy. What is more, an early outline evaluation of the genotyping costs and benefit was assessed.Results: Out of 35 patients treated with a taxane, six (17.1% had adverse neuropathy events. Pharmacogenomics analysis showed no correlation between candidate gene polymorphisms and toxicity, except for the XRCC3 AG+GG allele [OR 2.61 (95% CI: 0.91–7.61] which showed a weak significant trend of risk of neurotoxicities vs. the AG allele [OR 1.52 (95% CI: 0.51–4.91] P = 0.03.Summary: Based on our experimental results and data from the literature, we propose a useful and low-cost genotyping panel assay for the prevention of toxicity in patients undergoing taxane-based therapy. With the individual pharmacogenomics profile, clinicians will have additional information to plan the better treatment for their patients to minimize toxicity and maximize benefits, including determining cost-effectiveness for national healthcare sustainability.

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

Energy Technology Data Exchange (ETDEWEB)

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

2017-01-15

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Vascular toxicity of urea, a new “old player” in the pathogenesis of chronic renal failure induced cardiovascular diseases

Science.gov (United States)

D’Apolito, Maria; Brownlee, Michael; Maffione, Angela Bruna; Colia, Anna Laura; Sacco, Michele; Ferrara, Pietro; Pettoello-Mantovani, Massimo

2017-01-01

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure. PMID:29483797

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

Science.gov (United States)

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

2017-10-01

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

The Industrial Toxics Project: Targeting chemicals for environmental results

International Nuclear Information System (INIS)

Burch, W.M.

1991-01-01

In September, 1990, the Administrator of the US Environmental Protection Agency committed the Agency to a program of targeting chemicals for multi-media risk reduction activities through pollution prevention. The Industrial Toxics Project will place emphasis on obtaining voluntary commitments from industry to reduce releases of toxic chemicals to the air, water, and land with a goal of reducing releases nationwide by 33% by 1992 and 50% by 1995. An initial list of 18 chemicals have been selected based on recommendations from each Agency program. The chemicals selected are subject to reporting under the Toxic Chemical Release Inventory Program which will provide the basis for tracking progress. The chemicals are characterized by high production volume, toxicity and releases and present the potential for significant risk reduction through pollution prevention. This presentation will discuss the focus and direction of this new initiative

The management of acute and chronic pancreatitis.

Science.gov (United States)

Banks, Peter A; Conwell, Darwin L; Toskes, Phillip P

2010-02-01

Pancreatitis, which is most generally described as any inflammation of the pancreas, is a serious condition that manifests in either acute or chronic forms. Chronic pancreatitis results from irreversible scarring of the pancreas, resulting from prolonged inflammation. Six major etiologies for chronic pancreatitis have been identified: toxic/ metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, and obstruction. The most common symptom associated with chronic pancreatitis is pain localized to the upper-to-middle abdomen, along with food malabsorption, and eventual development of diabetes. Treatment strategies for acute pancreatitis include fasting and short-term intravenous feeding, fluid therapy, and pain management with narcotics for severe pain or nonsteroidal anti-inflammatories for milder cases. Patients with chronic disease and symptoms require further care to address digestive issues and the possible development of diabetes. Dietary restrictions are recommended, along with enzyme replacement and vitamin supplementation. More definitive outcomes may be achieved with surgical or endoscopic methods, depending on the role of the pancreatic ducts in the manifestation of disease.

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

Directory of Open Access Journals (Sweden)

Lorenzo Falchi

2016-02-01

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

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

Science.gov (United States)

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

2016-01-01

The B-cell receptor (BCR) signaling inhibitors ibrutinib and idelalisib are revolutionizing the treatment of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. These oral agents, both alone and in combination with other drugs, have shown remarkable clinical activity in relapsed or refractory CLL across all risk groups, and have been approved by the Food and Drug Administration for this indication. Preliminary data suggest that an even greater benefit can be expected in treatment-naïve CLL patients. Both ibrutinib and idelalisib are well tolerated by most patients, including older, frailer individuals. Toxicities are usually mild and self-resolving. Clinicians must, however, be aware of a number of peculiar adverse events, the effects of which can be severe enough to limit the clinical use of these agents. In this review, we survey the salient aspects of the pharmacology and clinical experience with the use of BCR signaling inhibitors for the treatment of patients with CLL. We next focus on both the most common and the most clinically significant toxicities associated with these drugs. PMID:26977270

Role of oxidative stress in cadmium toxicity and carcinogenesis

International Nuclear Information System (INIS)

Liu Jie; Qu Wei; Kadiiska, Maria B.

2009-01-01

Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-κB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.

The use of inexpensive broad spectrum lower toxicity therapeutics in chronic lymphocytic leukemia.

Science.gov (United States)

Marjanovic, Goran

2017-01-01

The use of new and highly efficient targeted therapies for chronic lymphocytic leukemia (CLL) is costly and out of reach for many health care systems. On the other hand, in recent years, few inexpensive, broad-spectrum low-toxicity therapeutics have proven to be effective both in the preclinical and clinical settings. In early-stage CLL, the use of 2000 mg of epigallocatechin-3-gallate (EGCG) from the green tea extract twice a day was able to reduce the absolute leukocyte count. Supplementation of >2000 IU/day of Vitamin D in early low-risk CLL patients is able to delay disease progression and postpone the moment of initiation of the first treatment. The doses of both vitamin D and EGCG were shown to be safe in older patients. Vitamin D, EGCG and Curcumin, either as monotherapy or in combination, have additive and synergistic effects with conventional chemotherapy. Further observations have identified the improvement of response to rituximab-fludarabine-cyclophosphamide (R-FC) therapy with concomitant administration of statin and aspirin combination in relapsed/refractory CLL. Finally, high dose dexamethasone with 40mg/m 2 /day for 4 days, every 28 days, either alone or with monoclonal antibody, might be used as a salvage therapy or for debulking before transplantation in refractory/resistant cases. Dexamethasone therapy is followed by transient response and high rate of infections, but fluid retention and other toxicities are lower compared to high dose methylprednisolone schedules. The low cost therapeutics discussed in this review could not be a substitute for the more effective targeted therapies, but their use in every day practice might postpone the need for early implementation of new and costly medications.

Uranium: biokinetics and toxicity

International Nuclear Information System (INIS)

Menetrier, F.; Renaud-Salis, V.; Flury-Herard, A.

2000-01-01

This report was achieved as a part of a collaboration with the Fuel Cycle Direction. Its aim was to give the state of the art about: the behaviour of uranium in the human organism (biokinetics) after ingestion, its toxicity (mainly renal) and the current regulation about its incorporation. Both in the upstream and in the downstream of the fuel cycle, uranium remains, quantitatively, the first element in the cycle which is, at the present time, temporarily disposed or recycled. Such a considerable quantity of uranium sets the problem of its risk on the health. In the long term, the biosphere may be affected and consequently the public may ingest water or food contaminated with uranium. In this way, radiological and chemical toxicity risk may be activated. This report emphasizes: the necessity of confirming some experimental and epidemiological biokinetic data used or not in the ICRP models. Unsolved questions remain about the gastrointestinal absorption according to chemical form (valency state, mixtures...), mass and individual variations (age, disease) further a chronic ingestion of uranium. It is well established that uranium is mainly deposited in the skeleton and the kidney. But the skeleton kinetics following a chronic ingestion and especially in some diseases has to be more elucidated; the necessity of taking into account uranium at first as a chemical toxic, essentially in the kidney and determining the threshold of functional lesion. In this way, it is important to look for some specific markers; the problem of not considering chemical toxicity of uranium in the texts regulating its incorporation

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

Science.gov (United States)

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

2008-01-01

In order to estimate acute-to-chronic toxicity ratios (ACRs) relevant to a coldwater stream community, we exposed rainbow trout (Oncorhynchus mykiss) to cadmium (Cd), lead (Pb), and zinc (Zn) in 96-h acute and 60+ day early-life stage (ELS) exposures. We also tested the acute and sublethal responses of a mayfly (Baetis tricaudatus) and a midge (Chironomus dilutus, formerly C. tentans) with Pb. We examine the statistical interpretation of test endpoints and the acute-to-chronic ratio concept. Increasing the number of control replicates by 2 to 3x decreased the minimum detectable differences by almost half. Pb ACR estimates mostly increased with increasing acute resistance of the organisms (rainbow trout ACRs results that used larger and older fish in their acute tests. ?? 2007 GovernmentEmployee: U.S. Geological Survey.

The toxicity of particles from combustion processes

International Nuclear Information System (INIS)

Henderson, R.F.; Mauderly, J.L.

1991-01-01

The pulmonary toxicity of inhaled particles will depend on their size, solubility and inherent toxicity. Many combustion-derived particles, such as soot and fly ash, are of a respirable size and, being poorly soluble, are retained for prolonged periods in the lung. The acute toxicity of fly ash from coal combustion was compared to that of a known toxic particle, alpha-quartz, by exposures of rats to 35 mg/m 3 of each type of particle for 7 hr/day, 5 days/wk for 4 wk. The acute pulmonary toxicity was measured by analysis of bronchoalveolar lavage fluid. One year after the exposures, fibrosis with granulomas was observed in the quartz-exposed rats, while little or no fibrosis developed in the fly-ash-exposed rats. The toxicity of soot from diesel exhaust was determined by chronic (30 mo) exposures of rats, 7 hr/day, 5 days/wk to exhaust containing 0.35, 3.5 or 7.0 mg/m 3 soot. The two higher exposures caused persistent pulmonary inflammation, fibrosis and neoplasmas. Rats exposed to the lowest concentration demonstrated no toxic responses and there was no life shortening caused by any exposure. Ongoing comparative studies indicate that pure carbon black particles cause responses similar to those caused by diesel exhaust, indicating that much of the toxicity induced by the diesel soot results from the presence of the large lung burdens of carbonaceous particles

Wild lettuce (Lactuca virosa) toxicity.

Science.gov (United States)

Besharat, Sima; Besharat, Mahsa; Jabbari, Ali

2009-01-01

Wild lettuce (Lactuca virosa) can cause toxic effects when eaten. Wild lettuce grows in the north of Iran and some natives consume it unaware of its adverse side effects. We describe eight patients with manifestations of wild lettuce toxicity, admitted to a general hospital affiliated to the Golestan University of Medical Sciences. All the patients recovered (although one had to spend 48 h in the intensive care unit) and no chronic complications were reported. A clinical suspicion of toxicity caused by wild lettuce intake and an accurate history formed the basis of the diagnosis. Conservative treatment, vital sign monitoring, control of patient intake and output, and reducing patient agitation provided the basis for treatment.

Identification of causes of oil sands coke leachate toxicity

International Nuclear Information System (INIS)

Puttaswamy, N.; Liber, K.

2010-01-01

The potential causes of oil sands coke leachate toxicity were investigated. Chronic 7-day toxicity tests were conducted to demonstrate that oil sands coke leachates (CL) are acutely toxic to Ceriodaphnia dubia (C. dubia). CLs were generated in a laboratory to perform toxicity identification evaluation (TIE) tests in order to investigate the causes of the CL toxicity. The coke was subjected to a 15-day batch leaching process at 5.5 and 9.5 pH values. The leachates were then filtered and used for chemical and toxicological characterization. The 7-day estimates for the C. dubia survival were 6.3 for a pH of 5.5 and 28.7 per cent for the 9.5 CLs. The addition of EDTA significantly improved survival and reproduction in a pH of 5.5 CL, but not in a pH of 9.5 CL. The toxicity of the pH 5.5 CL was removed with a cationic resin treatment. The toxicity of the 9.5 pH LC was removed using an anion resin treatment. Toxicity re-appeared when nickel (Ni) and vanadium (V) were added back to the resin-treated CLs. Results of the study suggested that Ni and V were acting as primary toxicants in the pH 5.5 CL, while V was the primary cause of toxicity in the pH 9.5 CL.

Toxicities of selected substances to freshwater biota

Energy Technology Data Exchange (ETDEWEB)

Hohreiter, D.W.

1980-05-01

The amount of data available concerning the toxicity of various substances to freshwater biota is so large that it is difficult to use in a practical situation, such as environmental impact assessment. In this document, summary tables are presented showing acute and/or chronic toxicity of selected substances for various groups of aquatic biota. Each entry is referenced to its original source so that details concerning experimental conditions may be consulted. In addition, general information concerning factors modifying toxicity, synergisms, evidence of bioaccumulation, and water quality standards and criteria for the selected substances is given. The final table is a general toxicity table designed to provide an easily accessible and general indication of toxicity of selected substances in aquatic systems.

Chronic pancreatitis.

Science.gov (United States)

Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

2017-09-07

Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

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

Science.gov (United States)

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

2016-02-03

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

Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats.

Science.gov (United States)

Tian, Y E; Teng, Li-Rong; Wang, Zhen-Zuo; Zhao, Min; Meng, Qing-Fan; Lu, Jia-Hui; Tian, Jian-Ming; Zhang, Wei-Wei; Zheng, Xiaoyi; Wang, D I; Teng, LE-Sheng

2015-06-01

Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non-addictive agent for the treatment of bone cancer pain.

Hepatic toxicity resulting from cancer treatment

International Nuclear Information System (INIS)

Lawrence, Theodore S.; Robertson, John M.; Anscher, Mitchell S.; Jirtle, Randy L.; Ensminger, William D.; Fajardo, Luis F.

1995-01-01

Radiation-induced liver disease (RILD), often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites approximately 2 weeks to 4 months after hepatic irradiation. There has been a renewed interest in hepatic irradiation because of two significant advances in cancer treatment: three dimensional radiation therapy treatment planning and bone marrow transplantation using total body irradiation. RILD resulting from liver radiation can usually be distinguished clinically from that resulting from the preparative regime associated with bone marrow transplantation. However, both syndromes demonstrate the same pathological lesion: veno-occlusive disease. Recent evidence suggests that elevated transforming growth factor β levels may play a role in the development of veno-occlusive disease. Three dimensional treatment planning offers the potential to determine the radiation dose and volume dependence of RILD, permitting the safe delivery of high doses of radiation to parts of the liver. The chief therapy for RILD is diuretics, although some advocate steroids for severe cases. The characteristics of RILD permit the development of a grading system modeled after the NCI Acute Common Toxicity Criteria, which incorporates standard criteria of hepatic dysfunction

Development of a database: DACTARI for a radio-toxic element ranking methodology

International Nuclear Information System (INIS)

Ansoborlo, E.; Santucci, C.; Grouiller, J.P.; Boucher, L.; Fluery-Herard, A.; Menetrier, F.; Comte, A.; Cook, E.; Moulin, V.

2007-01-01

Dosimetric impact studies aim at evaluating potential radiological effects of chronic or acute releases from nuclear facilities. A methodology for ranking radionuclides (RN) in terms of their health-related impact on the human population was first developed at CEA with specific criteria for each RN that could be applied to a variety of situations. It is based, in particular, on applying physico-chemical criteria to the complete RN inventory (present in the release or in the source term) and on applying norms related to radiation protection and chemical toxicology. The initial step consisted in identifying and collecting data necessary to apply the methodology, with reference to a previous database of long-lived radionuclides (LLRN, with half-lives ranging from 30 to 10 14 y) containing 95 radionuclides. The initial results have allowed us to identify missing data and revealed the need to complete the study for both toxic and radio-toxic aspects. This led us to the next step, developing a specific database, Database for Chemical Toxicity and Radiotoxicity Assessment of RadIonuclides (DACTARI), to collect data on chemical toxicity and radiotoxicity, including acute or chronic toxicity, the chemical form of the compounds, the contamination route (ingestion, inhalation), lethal doses, target organs, intestinal and maternal-foetal transfer, drinking water guidelines and the mutagenic and carcinogenic properties. (authors)

A dose-escalation trial with the adaptive radiotherapy process as a delivery system in localized prostate cancer: Analysis of chronic toxicity

International Nuclear Information System (INIS)

Brabbins, Donald; Martinez, Alvaro; Yan Di; Lockman, David; Wallace, Michell; Gustafson, Gary; Chen, Peter; Vicini, Frank; Wong, John

2005-01-01

Purpose: To evaluate the validity of the chosen adaptive radiotherapy (ART) dose-volume constraints while testing the hypothesis that toxicity would not be greater at higher tumor dose levels. Materials and methods: In the ART dose escalation/selection trial, treatment was initiated with a generic planning target volume (PTV) formed as a 1-cm expansion of the clinical target volume (CTV). After the first week of therapy, the patient was replanned with a patient-specific PTV, constructed with CT and electronic portal images obtained in the first 4 days of treatment. A new multileaf collimator beam aperture was used. A minimum dose prescribed to the patient-specific PTV, ranging 70.2-79.2 Gy, was determined on the basis of the following rectal and bladder constraints: 82 Gy, 75.6 Gy, 75.6 Gy, and the maximum bladder dose is 85 Gy. A conformal four-field and/or intensity-modulated radiotherapy (IMRT) technique was used. Independent reviewers scored toxicities. The worst toxicity score seen was used as per the Common Toxicity Criteria grade scale (version 2). We divided the patients into three separate groups: 70.2-72 Gy, >72-75.6 Gy, and >75.6-79.2 Gy. Toxicities in each group were quantified and compared by the Pearson chi-squared test to validate our dose escalation/selection model. Grades 0, 1, 2, and 3 were censored as none vs. each category and none vs. any. Results: We analyzed patients with follow-up greater than 1 year. The mean duration of follow-up was 29 months (range, 12-46 months). We report on 280 patients, mean age 72 years (range, 51-87 years). Only 60 patients received adjuvant hormones. Mean pretreatment prostate-specific antigen level was 9.3 ng/mL (range, 0.6-120 ng/mL). Mean Gleason score was 6 (range, 3-9). The lowest dose level was given to 49 patients, the intermediate dose to 131 patients, and 100 patients received the highest dose escalation. One hundred eighty-one patients (65%) were treated to a prostate field only and 99 patients (35%) to

Chronic arsenic toxicity in Bangladesh and West Bengal, India--a review and commentary.

Science.gov (United States)

Rahman, M M; Chowdhury, U K; Mukherjee, S C; Mondal, B K; Paul, K; Lodh, D; Biswas, B K; Chanda, C R; Basu, G K; Saha, K C; Roy, S; Das, R; Palit, S K; Quamruzzaman, Q; Chakraborti, D

2001-01-01

Fifty districts of Bangladesh and 9 districts in West Bengal, India have arsenic levels in groundwater above the World Health Organization's maximum permissible limit of 50 microg/L. The area and population of 50 districts of Bangladesh and 9 districts in West Bengal are 118,849 km2 and 104.9 million and 38,865 km2 and 42.7 million, respectively. Our current data show arsenic levels above 50 microg/ L in 2000 villages, 178 police stations of 50 affected districts in Bangladesh and 2600 villages, 74 police stations/blocks of 9 affected districts in West Bengal. We have so far analyzed 34,000 and 101,934 hand tube-well water samples from Bangladesh and West Bengal respectively by FI-HG-AAS of which 56% and 52%, respectively, contained arsenic above 10 microg/L and 37% and 25% arsenic above 50 microg/L. In our preliminary study 18,000 persons in Bangladesh and 86,000 persons in West Bengal were clinically examined in arsenic-affected districts. Of them, 3695 (20.6% including 6.11% children) in Bangladesh and 8500 (9.8% including 1.7% children) in West Bengal had arsenical dermatological features. Symptoms of chronic arsenic toxicity developed insidiously after 6 months to 2 years or more of exposure. The time of onset depends on the concentration of arsenic in the drinking water, volume of intake, and the health and nutritional status of individuals. Major dermatological signs are diffuse or spotted melanosis, leucomelanosis, and keratosis. Chronic arsenicosis is a multisystem disorder. Apart from generalized weakness, appetite and weight loss, and anemia, our patients had symptoms relating to involvement of the lungs, gastrointestinal system, liver, spleen, genitourinary system, hemopoietic system, eyes, nervous system, and cardiovascular system. We found evidence of arsenic neuropathy in 37.3% (154 of 413 cases) in one group and 86.8% (33 of 38 cases) in another. Most of these cases had mild and predominantly sensory neuropathy. Central nervous system involvement

Toxic effects of formalin-treated cadaver on medical students, staff ...

African Journals Online (AJOL)

Background: Formaldehyde can be toxic, allergenic and carcinogenic. Evaporation of formaldehyde from formalin-treated cadavers in the anatomy dissection rooms can produce high exposure. This study was conducted to assess acute and chronic toxic effects of formalin-treated cadavers on medical students, staff ...

Overview of toxicity data and risk assessment methods for evaluating the chemical effects of depleted uranium compounds

International Nuclear Information System (INIS)

Hartmann, H.M.; Monette, F.A.; Avci, H.I.

2000-01-01

In the United States, depleted uranium is handled or used in several chemical forms by both governmental agencies and private industry (primarily companies producing and machining depleted uranium metal for military applications). Human exposure can occur as a result of handling these compounds, routine low-level effluent releases to the environment from processing facilities, or materials being accidentally released from storage locations or during processing or transportation. Exposure to uranium can result in both chemical and radiological toxicity, but in most instances chemical toxicity is of greater concern. This article discusses the chemical toxic effects from human exposure to depleted uranium compounds that are likely to be handled during the long-term management and use of depleted uranium hexafluoride (UF 6 ) inventories in the United States. It also reviews representative publications in the toxicological literature to establish appropriate reference values for risk assessments. Methods are described for evaluating chemical toxicity caused by chronic low-level exposure and acute exposure. Example risk evaluations are provided for illustration. Preliminary results indicate that chemical effects of chronic exposure to uranium compounds under normal operating conditions would be negligibly small. Results also show that acute exposures under certain accident conditions could cause adverse chemical effects among the populations exposed.

Integrated fate and toxicity assessment for site contaminants

International Nuclear Information System (INIS)

MacDonell, Margaret; Peterson, John; Finster, Molly; Douglas, R.

2007-01-01

Understanding the fate and toxicity of environmental contaminants is essential to framing practical management decisions. Forms and bioavailable concentrations often change over time due to natural physical, chemical, and biological processes. For some sites, hundreds of contaminants may be of initial interest, and even small projects can involve a substantial number of contaminants. With multiple assessments common, attention to effectiveness and efficiency is important, and integrating fate and toxicity information provides a valuable way to focus the analyses. Fate assessments help identify what forms may be present where and when, while toxicity information indicates what health effects could result if people were exposed. The integration process is illustrated by an application for the Hanford site, to support long-term management decisions for the cesium and strontium capsules. Fate data, health-based benchmarks, and related toxicity information were effectively combined to indicate performance targets for chemicals and radionuclides identified for capsule leachate that could migrate to groundwater. More than 50 relevant benchmarks and toxicity context were identified for 15 of the 17 study contaminants; values for chronic drinking water exposure provided the common basis for selected indicators. For two chemicals, toxicity information was identified from the scientific literature to guide the performance targets. (authors)

The results of the toxicity and hazard studies of isopropyl meta-carborane with single administration to laboratory animals

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Yushkov G.G.

2018-04-01

Full Text Available Intensive research on the chemistry of borohydrides and the creation of high-energy fuels led to the discovery of a completely new type of organoboron compounds, which were collectively called carboranes. Taking into account the scope of application of organoboron compounds in various branches of human economic activity, we present for publication the quantitative data of a toxicological study of the higher isomer of carboranes of isopropyl meta-carborane at the level of a single injection into the laboratory animals through the mouth and lungs. Background. Supplementing data on toxicity and the hazard of organoboron compounds requires the study of the response of the organism to the action of isopropyl meta-carborane. The purpose of the study: identification of possible features and specificity of the toxic effect of carboranes on the example of isopropyl meta-carborane. Methods. The object of the study is nonlinear laboratory animals: rats, mice and rabbits contained in standard vivarium conditions, with observance of the rules of humane treatment of animals. Traditional methods of research (physiological, hematological, morphological have been used. Statistical processing of data was carried out using the programs «Microsoft Office Excel 2007» and «Biostat». Differences were considered statistically significant at p ≤ 0.05, using a parametric test. Results. Acute toxicity parameters were obtained, which allowed the substance to be classified as moderately hazardous (3rd hazard class according to GOST 12.1.007, which does not have selective irritant, pneumotoxic and fibrogenic effects. Conclusion. Thus, the predominant influence of the substance is established objectively with a single exposure to the blood system as its toxicological feature, and its effect on spermatozoa is a specificity of the action, which stimulates the study of this carborane under conditions of chronic administration to the animals.

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

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Abidemi J. Akindele

2018-01-01

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

[Morphologic characteristic of chronic toxic hepatitis for treatment with Neoselen].

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Isroilov, R I; Salikhodzhaeva, U Sh

2011-01-01

The purpose of the given research work was to study the features of morphologic changes arising for treatment of chronic hepatitis with Neoselen. It was established a picture of chronic active hepatitis in the liver of rats with the following development of chronic persisting hepatitis by the 40 daily administration of heliotrine and its transmission into cirrhosis in a certain part of animals. Hepatic cirrhosis has a small nodal portal character by its pathognomonic morphologic signs. A noticeable remittance of destructive necrotic changes in hepatic parenchymatous elements and reduction in a volume of proliferative inflammatory infiltration with an acceleration in process of its fibrozation in only periportal zones of hepatic lobules found to be for treatment of chronic hepatitis with Neoselen. That prevents from transmission of chronic hepatitis into cirrhosis in a greater part of animals that is a morphologic evidence of importance of selenium in a restorative process of biologic membranes and its involvement in a remittance process of destructive and inflammatory changes in the liver and prevention from development of agressive hepatitis and its transmission into cirrhosis.

Mechanisms of the Testis Toxicity Induced by Chronic Exposure to Mequindox

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Qianying Liu

2017-09-01

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

Development of a strontium chronic effects benchmark for aquatic life in freshwater.

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McPherson, Cathy A; Lawrence, Gary S; Elphick, James R; Chapman, Peter M

2014-11-01

There are no national water-quality guidelines for strontium for the protection of freshwater aquatic life in North America or elsewhere. Available data on the acute and chronic toxicity of strontium to freshwater aquatic life were compiled and reviewed. Acute toxicity was reported to occur at concentrations ranging from 75 mg/L to 15 000 mg/L. The majority of chronic effects occurred at concentrations above 11 mg/L; however, calculation of a representative benchmark was confounded by results from 4 studies indicating that chronic effects occurred at lower concentrations than all other studies, in 2 cases below background concentrations reported for US and European streams. Two of these studies, including 1 reporting effects below background concentrations, were repeated and found not to be reproducible; chronic effects occurred at considerably higher strontium concentrations than in the original studies. Studies with narrow-mouthed toad and goldfish were not repeated; both studies reported chronic effects below background concentrations, and both studies had been conducted by the authors of 1 of the 2 studies that were repeated and shown to be nonreproducible. Studies by these authors (3 of the 4 confounding studies), conducted over 30 yr ago, lacked detail in reporting of methods and results. It is thus likely that repeating the toad and goldfish studies would also have resulted in a higher strontium effects concentration. A strontium chronic effects benchmark of 10.7 mg/L that incorporates the results of additional testing summarized in the present study is proposed for freshwater environments. © 2014 SETAC.

Chronic total coronary occlusion: treatment results.

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Kirk Christensen, Martin; Freeman, Phillip Fischer; Rasmussen, Jeppe Groendal; Villadsen, Anton Boel; Raungaard, Bent; Eggert Jensen, Svend; Thuesen, Leif

2017-08-01

To describe the clinical and procedural coronary chronic total occlusion (CTO) treatment results in a Nordic PCI centre during the implementation of a CTO treatment program. In a retrospective registry study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart failure score, (3) lesion complexity and (4) adverse events during hospital stay and three months following the index procedure. The study cohort included 503 patients (594 lesions). From 2010 to 2013 96% of procedures were performed with antegrade wire-escalation technique and 4% performed using retrograde techniques, from 2013-2016 the corresponding numbers were 83% and 17.0%. The procedural success rate was 69%, increasing from 64% before to 72% (p = .06) after routinely using the retrograde approach. No individual patient characteristic, lesion variable or score was strongly associated with procedural success or failure. There were 4% serious procedure related complications. In patients with PCI of a CTO lesion only, 87% were in CCS or NYHA functional class ≥2 before the index procedure vs. 22% at follow-up. Routine use of retrograde techniques tended to increase the procedural success rate. Clinical results after three months were acceptable, but the complication rate was higher than for non-CTO PCI. Individual patient and lesion characteristics had a low predictability for procedural success. Therefore, clinical symptoms, objective signs of myocardial ischemia and procedural risk should be focus points in coronary chronic total occlusion treatment strategies.

Air toxic emissions from burning of biomass globally-preliminary results

International Nuclear Information System (INIS)

Ward, D.E.; Hao, W.M.

1992-01-01

Emissions of trace gases, particles, and air toxic substances in the smoke plumes from biomass fires are of importance to global climate change. The potential impact of the air toxic emissions on the human population of specific regions globally is another major concern. The toxic materials are produced in high concentrations in areas of heavy biomass burning, e.g., Amazon Basin and Central/southern Africa. We provide new estimates of air toxics based on the combustion efficiency (percent of total carbon released as CO 2 ) for fires burning in different ecosystems on a global basis. Estimates of total biomass consumed on a global basis range from 2 to 10 Pg (1 petagram = 10 15 g) per year. We apply emission factors for various air toxics (g of emission released per kg of fuel consumed) to the estimate of global biomass consumption of 6.4 Pg per year. The principal air toxics analyzed in this paper include: Total particulate matter, CO, formaldehyde, acetaldehyde, acrolein, benzene, toluene, o-xylene, m, p-xylene, benzo[a]pyrene, and polycyclic organic material. The total emissions calculated for these materials on a yearly global basis are: 75, 362, 4.9, 1.5, 1.5, 2.1, 2.1, 0.3, 0.6, 0.001, 0.026, Tg (1 teragram = 10 12 g) per year, respectively. Biomass burning in the United States contributes less than 3% to the total global emissions

Neurophysiological Effects of Chronic Indoor Environmental Toxic Mold Exposure on Children

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Ebere C. Anyanwu

2003-01-01

Full Text Available The phenomenon of building-related diseases is attracting much research interest in recent years because of the extent to which it affects people with compromised immune systems, especially children. In this study, we reported the neurological findings in children who attended our Center because of chronic exposure to toxic molds. Clinical neurological and neurobehavioral questionnaires were administered with the cooperation of the children�s parents. The children then underwent a series of neurophysiological tests including electroencephalogram (EEG, brainstem evoked potential (BAEP, visual evoked potential (VEP, and somatosensory evoked potential (SSEP. The results showed high levels of abnormalities in the analysis of the subjective responses derived from the questionnaires. The EEG examination was abnormal in seven out of ten of the patients compared to the controls with only one in ten with episodes of bihemispheric sharp activity. In all the patients, there was frontotemporal theta wave ativity that seemed to indicate diffuse changes characteristic of metabolic encephalopathies. Also, there was highly marked 1 to 3 Hz delta activity that was asymmetrical in the right hemisphere of the brain in three out of ten patients. The waveforms of BAEP showed abnormalities in 90% of the patients with both 15’ and 31’ check sizes compared to none in the controls. There were significant delays in waveform V in a majority of the patients representing dysfunctional cognitive process and conductive hearing loss in both ears. VEP showed clear abnormalities in four in ten of the patients with P100 amplitudes and latencies decreased bilaterally. In all the patients, there was slowing of conduction in the right tibial at an average of 36.9 ms and there was significant decrease in amplitude of response at the proximal stimulation site. Sensory latencies obtained in the median, ulnar, and sural nerves bilaterally showed abnormalities in five out of ten

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Toxicity of indium arsenide, gallium arsenide, and aluminium gallium arsenide

International Nuclear Information System (INIS)

Tanaka, Akiyo

2004-01-01

Gallium arsenide (GaAs), indium arsenide (InAs), and aluminium gallium arsenide (AlGaAs) are semiconductor applications. Although the increased use of these materials has raised concerns about occupational exposure to them, there is little information regarding the adverse health effects to workers arising from exposure to these particles. However, available data indicate these semiconductor materials can be toxic in animals. Although acute and chronic toxicity of the lung, reproductive organs, and kidney are associated with exposure to these semiconductor materials, in particular, chronic toxicity should pay much attention owing to low solubility of these materials. Between InAs, GaAs, and AlGaAs, InAs was the most toxic material to the lung followed by GaAs and AlGaAs when given intratracheally. This was probably due to difference in the toxicity of the counter-element of arsenic in semiconductor materials, such as indium, gallium, or aluminium, and not arsenic itself. It appeared that indium, gallium, or aluminium was toxic when released from the particles, though the physical character of the particles also contributes to toxic effect. Although there is no evidence of the carcinogenicity of InAs or AlGaAs, GaAs and InP, which are semiconductor materials, showed the clear evidence of carcinogenic potential. It is necessary to pay much greater attention to the human exposure of semiconductor materials

Pharmacokinetic drivers of toxicity for basic molecules: Strategy to lower pKa results in decreased tissue exposure and toxicity for a small molecule Met inhibitor

International Nuclear Information System (INIS)

Diaz, Dolores; Ford, Kevin A.; Hartley, Dylan P.; Harstad, Eric B.; Cain, Gary R.; Achilles-Poon, Kirsten; Nguyen, Trung; Peng, Jing; Zheng, Zhong; Merchant, Mark; Sutherlin, Daniel P.; Gaudino, John J.; Kaus, Robert; Lewin-Koh, Sock C.; Choo, Edna F.; Liederer, Bianca M.; Dambach, Donna M.

2013-01-01

Several toxicities are clearly driven by free drug concentrations in plasma, such as toxicities related to on-target exaggerated pharmacology or off-target pharmacological activity associated with receptors, enzymes or ion channels. However, there are examples in which organ toxicities appear to correlate better with total drug concentrations in the target tissues, rather than with free drug concentrations in plasma. Here we present a case study in which a small molecule Met inhibitor, GEN-203, with significant liver and bone marrow toxicity in preclinical species was modified with the intention of increasing the safety margin. GEN-203 is a lipophilic weak base as demonstrated by its physicochemical and structural properties: high LogD (distribution coefficient) (4.3) and high measured pKa (7.45) due to the basic amine (N-ethyl-3-fluoro-4-aminopiperidine). The physicochemical properties of GEN-203 were hypothesized to drive the high distribution of this compound to tissues as evidenced by a moderately-high volume of distribution (Vd > 3 l/kg) in mouse and subsequent toxicities of the compound. Specifically, the basicity of GEN-203 was decreased through addition of a second fluorine in the 3-position of the aminopiperidine to yield GEN-890 (N-ethyl-3,3-difluoro-4-aminopiperidine), which decreased the volume of distribution of the compound in mouse (Vd = 1.0 l/kg), decreased its tissue drug concentrations and led to decreased toxicity in mice. This strategy suggests that when toxicity is driven by tissue drug concentrations, optimization of the physicochemical parameters that drive tissue distribution can result in decreased drug concentrations in tissues, resulting in lower toxicity and improved safety margins. -- Highlights: ► Lower pKa for a small molecule: reduced tissue drug levels and toxicity. ► New analysis tools to assess electrostatic effects and ionization are presented. ► Chemical and PK drivers of toxicity can be leveraged to improve safety.

Toxicity of carbon nanotubes: A review.

Science.gov (United States)

Francis, Arul Prakash; Devasena, Thiyagarajan

2018-03-01

Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose. In addition, CNTs and/or associated contaminants were well known for oxidative stress, inflammation, apoptosis, pulmonary inflammation, fibrosis, and granuloma in lungs. The increased production of CNTs likely enhanced the possibility of its exposure in people. Studies on the toxicity of CNTs are mainly focused on the pulmonary effects after intratracheal administration, and only a few studies are reported about the toxicity of CNTs via other routes of exposure. So, it is essential to consider the chronic toxicity of CNTs before using them for various biomedical applications. This review focuses on the potential toxicities of CNTs.

European medicinal and edible plants associated with subacute and chronic toxicity part II: Plants with hepato-, neuro-, nephro- and immunotoxic effects.

Science.gov (United States)

Kristanc, Luka; Kreft, Samo

2016-06-01

A tremendous surge of public interest in natural therapies has been reported in the past several decades in both developing and developed countries. Furthermore, edible wild-growing plants whose use had long been associated with poverty and famine have also gained in popularity among people in developed countries. An important fraction of herbal products evade all control measures and are generally perceived as safe. However, this may not always be true. It is important to recognize that some plants are not associated with acute toxicity but rather produce more insidious problems, which develop only with long-term exposure. In this review, we continue a systematic analysis of the subacute and chronic toxicity associated with the use of herbal preparations. The hepato-, neuro-, nephro- and immunotoxicity of plant species that either grow natively or are cultivated in Europe are discussed in some detail. The basic concepts regarding the molecular mechanisms implicated in their nonacute toxicity and their pathophysiological, clinical and epidemiological characteristics are included. Among others, we discuss the hepatotoxicity of pyrrolizidine alkaloids, the nephrotoxicity of aristolochic acid, the lathyrism associated with neurotoxin swainsonine, thiamine depletion and thyroid dysfunction of herbal cause, and finally address also the immunosuppressive effects of cannabinoids. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of synthetic and natural toxicants on livestock.

Science.gov (United States)

Shull, L R; Cheeke, P R

1983-07-01

Synthetic and natural toxicants are constituents of soil, air, water and foodstuffs. Their impact on animal agriculture has resulted from acute and chronic intoxication and residues transferred into meat, dairy and poultry products. Recent advances in analytical chemistry and the sciences associated with toxicology have allowed better assessment of the hazard of toxicants on animals including man. Historically, natural toxicants (phytotoxins, mycotoxins and minerals) that are associated with many common feedstuffs accounted for toxicity episodes of epidemic proportions. Most synthetic chemicals (pesticides, nonpesticidal organic chemicals and drugs) have been introduced in increasing numbers since the 1940's. In the 1960's and '70's, recognition of the need to control their environmental distribution stimulated the introduction of numerous laws and regulations. In the last decade, several problematic synthetic chemicals have been banned, particularly those found to persist in the environment or those confirmed or suspected as carcinogens in humans. At the farm level, the development of various preventative management strategies has decreased the exposure of livestock to natural toxicants. In the future, the impact of natural toxicants on animal agriculture is expected to lessen as their existence, etiology and toxicology are determined. On the other hand, synthetic chemicals will continue to threaten animal health as greater numbers and quantities are released into the environment. These challenges should stimulate a greater involvement of animal scientists in toxicology.

Evaluation of Chronic Nanosilver Toxicity to Adult Zebrafish

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Roberta Pecoraro

2017-12-01

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

Acute and Chronic Effects of Tributyltin on the Mysid Acanthomysis sculpta (Crustacea, Mysidacea).

Science.gov (United States)

1986-05-01

juveniles . . . 19 12. Summary of chronic values in pg/L TBT . . . 26 viii INTRODUCTION Tributyltin ( TBT ) is commonly used as an antifouling toxicant in...juveniles was determined at 0 42-jig L TBT . Reproductive effects were the most sensitive sublethal indicator of TBT toxicity . A chronic value of 0.14-pgL...SI[CUmITV CLAShIFICATION OF THIS PASU M DAI &W- A comparison of TBT toxicity was performed using a TBT solution leached from painted panels

The Toxicity of Depleted Uranium

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Wayne Briner

2010-01-01

Full Text Available Depleted uranium (DU is an emerging environmental pollutant that is introduced into the environment primarily by military activity. While depleted uranium is less radioactive than natural uranium, it still retains all the chemical toxicity associated with the original element. In large doses the kidney is the target organ for the acute chemical toxicity of this metal, producing potentially lethal tubular necrosis. In contrast, chronic low dose exposure to depleted uranium may not produce a clear and defined set of symptoms. Chronic low-dose, or subacute, exposure to depleted uranium alters the appearance of milestones in developing organisms. Adult animals that were exposed to depleted uranium during development display persistent alterations in behavior, even after cessation of depleted uranium exposure. Adult animals exposed to depleted uranium demonstrate altered behaviors and a variety of alterations to brain chemistry. Despite its reduced level of radioactivity evidence continues to accumulate that depleted uranium, if ingested, may pose a radiologic hazard. The current state of knowledge concerning DU is discussed.

Liver cirrhosis as a result of chronic hepatitis C

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A. A. Sukhoruk

2014-01-01

Full Text Available The incidence of chronic hepatitis C in St. Petersburg is 124.4 per 100 000 population. The number of patients with liver cirrhosis is significant.Aim of this study: to examine the demographic, clinical and epidemiological characteristics of patients with cirrhosis in the results of chronic hepatitis C.Materials and methods: 100 patients with cirrhosis due to chronic hepatitis C in age 31–70 years were included. Patients with infection hepatitis viruses A and B, HIV, alcohol abuse, drug addicts, previously received antiviral therapy were excluded. Liver cirrhosis was diagnosed on the basis clinical, laboratory and instrumental investigations.Results: most patients (86,2% male and 81,7% female are socially adapted. In 23,2% of patients antibodies to hepatitis C virus were first detected simultaneously with the diagnosis of cirrhosis. Medical procedures were the most common route of infection (25,6% male and 57,1% female. Genotype 1 was dominant (65.7%. Viral load over 800 000 IU/ml was detected in 36,7% of patients. ALT activity was normal or not more than 2 upper limit of normal in 59% of patients, AST – 47%. Normal levels of total bilirubin were recorded in 37% of cases.Conclusions: the first detection of antibodies to hepatitis C virus at the stage of cirrhosis, absence of jaundice, normal or low cytolytic activity once again confirms the need for screening for markers of hepatitis C virus. Dominance of genotype 1 is probably due on the one hand with features routes of transmission, and the other – with the speed of transformation chronic hepatitis to cirrhosis.

Recovery of anaerobic digestion after exposure to toxicants. Final report

Energy Technology Data Exchange (ETDEWEB)

Yang, J.; Parkin, G.F.; Speece, R.E.

1979-12-01

The concept that methane fermentation cannot tolerate chronic or slug doses of toxicants has almost totally precluded methane fermentation as a viable contender for the treatment of industrial wastewaters. This study assayed a wide variety of toxicants, heavy metals, inorganic salts, organic chemicals, solvents, and antibiotics which are used in industrial processes and, therefore, appear in the industrial wastewaters therefrom. Toxicity was related to the reduction in methane production of a control containing no toxicant. The response of methane fermentation after exposure to a toxicant was assayed with unacclimated cultures as well as cultures which had been acclimated to increasing concentrations of the toxicant over long periods of time. The reversible nature of the toxicants was assayed by adding slug doses to plug flow anaerobic filters and recording gas production prior to, during, and after toxicant addition.

Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

International Nuclear Information System (INIS)

Korkmaz, A.; Yaren, H.; Kunak, I.; Uysal, B.; Kurt, B.; Topal, T.

2009-01-01

The pathogenesis of sulfur mustard (SM) toxicity is not fully understood, although it is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly (ADP-ribose) polymerase activation within the affected cell. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of SM poisoning in rats' lung. A total of 40 male SD rats were divided into 4 groups. Group 1 served as control and given 2 ml saline, three groups received single dose of mechlorethamine (MEC) (3.5 mg/kg subcutaneously) with the same time intervals. Group 2 received MEC only; group 3 received histone deacetylase (HDAC) inhibitor (Trichostatine A) (1 mg/kg) and group 4 received DNA methyl transferase (DNMT) inhibitor (5-Azacytidine) (0.02 mg/kg), intraperitoneally. MEC injection resulted in severe lung toxicity with strong interstitial and alveolar edema, hemorrhage, emphysematous changes as well as mild inflammatory cell infiltration and septal thickening. In group 3, the HDAC inhibitor significantly reduced interstitial and alveolar edema, hemorrhage and inflammatory cell infiltration. On the other hand, we have observed severe lung damage by using DNMT inhibitor (group 4). In HDAC inhibitor group, the results were close to sham group. In DNMT inhibitor group, however, lungs were worse than MEC group results. These preliminary results revealed that, SM itself and/or its intracellular metabolites may perturb the epigenetic environment of the affected cell in lung tissue. Hypothetically, MEC may cause HDAC induction leading to a variety of gene silencing. Trichostatine A can reduce the active enzyme level and can reactivate the already silenced genes. Further studies are needed to clarify the involvement of epigenetic perturbations in the pathogenesis of mustard toxicity.(author)

Toxicity evaluation of the effluent of the ammonium diuranate process proceeding from the Uranium Reconversion Cycle (IPEN/CNEN-SP)

International Nuclear Information System (INIS)

Osti, Silvio Cesar de

2001-01-01

This project was developed with the objective to evaluate the acute and chronic toxicity of the ammonium diuranate proceeding from the process used to obtain uranium hexafluoride (UF 6 ), substance which is necessary to produce fuel used by the IEA-R1-IPEN reactor. Five acute toxicity tests were done with Daphnia similis in which concentration values of EC(I)50;48h, between 0,39% and 0,57% of the effluent were determined, and other five with Danio rerio in which concentration values of EC(I)50;48h, between 0,06% and 0,07% of the effluent were determined. Three chronic toxicity tests with Selenastrum capricornutum were done, having found NOEC values for concentrations below 0,12% of the effluents. To determine the ion fluoride toxicity in the Daphnia similis, five acute toxicity tests were done in which values of EC(I)50;48h, between 263.90 mgL -1 and 292.82 mgL -1 were found. The acute toxicity tests done with D. similis demonstrated that the effluent toxicity persisted during its storage period. The acute toxicity test with D.rerio and chronic ones with S. capricornutum using the effluents after the ionic-replace treatment, which objective is to recover uranium for reuse, demonstrated the effluent toxicity persistency. (author)

Environmental Determinants of Chronic Disease and Medical Approaches: Recognition, Avoidance, Supportive Therapy, and Detoxification

International Nuclear Information System (INIS)

Sears, M.E.; Sears, M.E.; Genuis, S.J.

2012-01-01

The World Health Organization warns that chronic, non communicable diseases are rapidly becoming epidemic worldwide. Escalating rates of neuro cognitive, metabolic, autoimmune and cardiovascular diseases cannot be ascribed only to genetics, lifestyle, and nutrition; early life and ongoing exposures, and bio accumulated toxicants may also cause chronic disease. Contributors to ill health are summarized from multiple perspectives biological effects of classes of toxicants, mechanisms of toxicity, and a synthesis of toxic contributors to major diseases. Health care practitioners have wide-ranging roles in addressing environmental factors in policy and public health and clinical practice. Public health initiatives include risk recognition and chemical assessment then exposure reduction, remediation, monitoring, and avoidance. The complex web of disease and environmental contributors is amenable to some straightforward clinical approaches addressing multiple toxicants. Widely applicable strategies include nutrition and supplements to counter toxic effects and to support metabolism; as well as exercise and sweating, and possibly medication to enhance excretion. Addressing environmental health and contributors to chronic disease has broad implications for society, with large potential benefits from improved health and productivity.

hepatorenal toxicity studies of sub-chronic administration of calyx

African Journals Online (AJOL)

DR. AMINU

significant (p>0.05) increase in concentrations of total protein and albumin were observed in ... suggest that high dose of calyx extracts of H.sabdariffa may be toxic to liver and kidney. .... monitoring liver damage (Wada and Snell, 1962).

Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats

International Nuclear Information System (INIS)

Butenhoff, John L.; Chang, Shu-Ching; Olsen, Geary W.; Thomford, Peter J.

2012-01-01

Highlights: ► A two-year dietary toxicity and cancer bioassay was conducted with K + PFOS in rats. ► Hepatocellular hypertrophy was the main microscopic non-neoplastic finding. ► Hepatocellular adenoma was increased in males and females fed the high dose. ► Males fed high dose for 1 year had increased thyroid follicular cell adenoma. ► The latter finding is of equivocal relationship to treatment. -- Abstract: To investigate toxicity and neoplastic potential from chronic exposure to perfluorooctanesulfonate (PFOS), a two-year toxicity and cancer bioassay was conducted with potassium PFOS (K + PFOS) in male and female Sprague Dawley rats via dietary exposure at nominal K + PFOS concentrations of 0, 0.5, 2, 5, and 20 μg/g (ppm) diet for up to 104 weeks. Additional groups were fed 20 ppm for the first 52 weeks, after which they were fed control diet through study termination (20 ppm Recovery groups). Scheduled interim sacrifices occurred on Weeks 4, 14, and 53, with terminal sacrifice between Weeks 103 and 106. K + PFOS appeared to be well-tolerated, with some reductions in body weight occurring in treated rats relative to controls over certain study periods. Male rats experienced a statistically significant decreased trend in mortality with significantly increased survival to term at the two highest treatment levels. Decreased serum total cholesterol, especially in males, and increased serum urea nitrogen were consistent clinical chemistry observations that were clearly related to treatment. The principal non-neoplastic effect associated with K + PFOS exposure was in livers of males and females and included hepatocellular hypertrophy, with proliferation of endoplasmic reticulum, vacuolation, and increased eosinophilic granulation of the cytoplasm. Statistically significant increases in hepatocellular adenoma were observed in males (p = 0.046) and females (p = 0.039) of the 20 ppm treatment group, and all of these tumors were observed in rats surviving to

Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

International Nuclear Information System (INIS)

Hulshof, M.C.C.M; Crezee, J.; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J.J.B.; Richel, D.J.

2005-01-01

Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m 2 ) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea ≤ grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients with

Toxicity and first treatment results after of neoadjuvant thermal radiochemotherapy in operable oesophageal cancer

Energy Technology Data Exchange (ETDEWEB)

Hulshof, M C.C.M; Crezee, J; Zum Vorde sive Vording, P.; Geijssen, D; Lanschot van, J J.B.; Richel, D J [Academical Medical Center of Amsterdam (Netherlands)

2005-07-01

Full text: To demonstrate the toxicity and preliminary treatment results of neo-adjuvant regional hyperthermia combined with concurrent radiochemotherapy in oesophageal cancer. Background: In 2002 a phase I study was completed with neo-adjuvant regional hyperthermia combined with chemotherapy (cisplatin and etoposide) in patients with operable oesophageal cancer. It was concluded that hyperthermia was feasible. However, the toxicity of the concurrent chemotherapy was very high, resulting in only 31 % of patients receiving the planned three hyperthermia sessions and 27 % receiving not more than one hyperthermia session. Based on these results we planned to continue hyperthermia in a phase II study aiming at a decrease of (chemotherapy induced) toxicity and an improvement of response rate compared to previous radiochemotherapy studies. In August 2003 a phase II study was started combining five times regional hyperthermia with concurrent radiochemotherapy over a 4,5 weeks period consisting of weekly carboplatin (AUC = 2) and paclitaxel (50 mg/m{sup 2}) plus 41,4 Gy radiotherapy in 1.8 Gy daily fractions. Chemotherapy was infused during hyperthermia. An oesophagus resection was planned at 4-6 weeks after the end of radiotherapy. 28 patients have entered the study so far, 94 % with a T3 tumor and 59 % with N1 disease on echo-endosonography. Median follow-up is 9 months and 23 patients are evaluable for histological response. Toxicity was much less compared to the previous cisplatin/etoposide study; all five hyperthermia sessions were given in 88 % of patients (and 96 % had at least four sessions). No haematological toxicity was seen and nausea {<=} grade 2 in only 24 %. Dysphagia and weight loss during treatment were absent in 68 % and 81 % of patients respectively. A histological confirmed complete remission rate (CR) was found in 17 % and only residual microscopic tumor foci (Pmic) in an extra 33 %. Partial remission (PR) was accomplished in 33 %. Mean T90 in patients

Acute and chronic effects of organophosphate pesticides (Basudin ...

African Journals Online (AJOL)

Toxicity of basudin (an organophosphate pesticide) on the larval stages of the dominant amphibian; Ptychadena bibroni of the Niger Delta ecological zone of Nigeria was assessed using acute and chronic toxicity in the laboratory. Mortality and body glycogen levels were used as ecological endpoints. The American society ...

Chronic toxicity of ZnO nanoparticles, non-nano ZnO and ZnCl2 to Folsomia candida (Collembola) in relation to bioavailability in soil

International Nuclear Information System (INIS)

Kool, Pauline L.; Diez Ortiz, Maria; Gestel, Cornelis A.M. van

2011-01-01

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

Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

Science.gov (United States)

Lakshmanan, Hariprasath; Raman, Jegadeesh; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

2016-12-24

Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of in vivo toxicity, antioxidant and immunomodulatory activities of coconut, nipah and pineapple juice vinegars.

Science.gov (United States)

Mohamad, Nurul Elyani; Keong Yeap, Swee; Beh, Boon Keen; Romli, Muhammad Firdaus; Yusof, Hamidah Mohd; Kristeen-Teo, Ye Wen; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

2018-01-01

Vinegar is widely used as a food additive, in food preparation and as a food supplement. This study compared the phenolic acid profiles and in vivo toxicities, and antioxidant and immunomodulatory effects of coconut, nipah and pineapple juice vinegars, which were respectively prepared via a two-step fermentation using Saccharomyces cerevisiae 7013 INRA and Acetobacter aceti vat Europeans. Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4 + and CD8 + T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines. Overall, the data suggested that not all vinegar samples cause acute and sub-chronic toxicity in vivo. Moreover, the in vivo immunity and organ antioxidant levels were enhanced, to varying extents, by the phenolic acids present in the vinegars. The results obtained in this study provide appropriate guidelines for further in vivo bioactivity studies and pre-clinical assessments of vinegar consumption. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

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

Directory of Open Access Journals (Sweden)

Toyohisa Katsumata

2014-01-01

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

Haloacetonitriles: metabolism and toxicity.

Science.gov (United States)

Lipscomb, John C; El-Demerdash, Ebtehal; Ahmed, Ahmed E

2009-01-01

chronic) toxicity studies; the results of such well-planned, controlled, conducted, interpreted and published investigations would be valuable in establishing margins of safety for HANs in human health risk assessment.

Is Boric Acid Toxic to Reproduction in Humans? Assessment of the Animal Reproductive Toxicity Data and Epidemiological Study Results.

Science.gov (United States)

Duydu, Yalçın; Başaran, Nurşen; Ustündağ, Aylin; Aydın, Sevtap; Undeğer, Ulkü; Ataman, Osman Yavuz; Aydos, Kaan; Düker, Yalçın; Ickstadt, Katja; Waltrup, Brita Schulze; Golka, Klaus; Bolt, Hermann Maximilian

2016-01-01

Boric acid and sodium borates are classified as toxic to reproduction in the CLP Regulation under "Category 1B" with the hazard statement of "H360FD". This classification is based on the reprotoxic effects of boric acid and sodium borates in animal experiments at high doses. However, boron mediated reprotoxic effects have not been proven in epidemiological studies so far. The epidemiological study performed in Bandırma boric acid production plant is the most comprehensive published study in this field with 204 voluntarily participated male workers. Sperm quality parameters (sperm morphology, concentration and motility parameters), FSH, LH and testosterone levels were determined in all participated employees as the reproductive toxicity biomarkers of males. However, boron mediated unfavorable effects on reproduction in male workers have not been determined even in the workers under very high daily boron exposure (0.21 mg B/kg-bw/day) conditions. The NOAEL for rat reproductive toxicity is equivalent to a blood boron level of 2020 ng/g. This level is higher than the mean blood boron concentration (223.89 ± 69.49 ng/g) of the high exposure group workers in Bandırma boric acid production plant (Turkey) by a factor of 9. Accordingly, classifying boric acid and sodium borates under "Category 1B" as "presumed reproductive human toxicant in the CLP regulation seems scientifically not reasonable. The results of the epidemiological studies (including the study performed in China) support for a down-classification of boric acid from the category 1B, H360FD to category 2, H361d, (suspected of damaging the unborn child).

Sediment toxicity testing with the amphipod Ampelisca abdita in Calcasieu Estuary, Louisiana

Science.gov (United States)

Redmond, M.S.; Crocker, P.A.; McKenna, K.M.; Petrocelli, E.A.; Scott, K.J.; Demas, C.R.

1996-01-01

Discharges from chemical and petrochemical manufacturing facilities have contaminated portions of Louisiana's Calcasieu River estuary with a variety of organic and inorganic contaminants. As part of a special study, sediment toxicity testing was conducted to assess potential impact to the benthic community. Ten-day flow-through sediment toxicity tests with the amphipod Ampelisca abdita revealed significant toxicity at 68% (26 of 38) of the stations tested. A. abdita mortality was highest in the effluent-dominated bayous, which are tributaries to the Calcasieu River. Mortality was correlated with total heavy metal and total organic compound concentrations in the sediments. Ancillary experiments showed that sediment interstitial water salinity as low as 2.5 o/o-o did not significantly affect A. abdita's, response in the flow-through system; sediment storage for 7 weeks at 4??C did not significantly affect toxicity. Sediment toxicity to A. abdita was more prevalent than receiving water toxicity using three short-term chronic bioassays. Results suggest that toxicity testing using this amphipod is a valuable tool when assessing sediments containing complex contaminant mixtures and for assessing effects of pollutant loading over time. In conjunction with chemical analyses, the testing indicated that the effluent-dominated, brackish bayous (Bayou d'Inde and Bayou Verdine) were the portions of the estuary most impacted by toxicity.

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

Science.gov (United States)

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

2011-11-01

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

Work disability resulting from chronic health conditions.

Science.gov (United States)

Lerner, Debra; Allaire, Saralynn H; Reisine, Susan T

2005-03-01

To describe current programs and policies for addressing work disability among adults with chronic health conditions, and to identify opportunities for new research aimed at reducing the problem. The authors conducted secondary data analysis and a literature review. Millions of Americans with a chronic health condition have a work disability or are at risk of developing one. This public health problem is costing hundreds of billions of dollars a year nationally in lost productivity and diminishing the quality of life of millions of Americans. The medical care system, employers, and government--three traditional sources of help for adults with chronic health problems--are not sufficiently oriented toward the primary or secondary prevention of work disability. New research is urgently needed to reduce the burden of work disability on individuals and society.

Sacha Inchi (Plukenetia volubilis L. powder: acute toxicity, 90 days oral toxicity study and micronucleus assay in rodents

Directory of Open Access Journals (Sweden)

Idania Rodeiro

2018-02-01

Full Text Available Context: Sacha Inchi has been consumed for years by indigenous peoples. Meanwhile, its toxicological potential has not been sufficiently studied. Aims: To assess the acute, sub-chronic toxicity and genotoxicity evaluation of Sacha Inchi powder obtained from Plukenetia volubilis L. Methods: A dose of 2000 mg/kg was orally administered to rats and mice and toxicity symptoms for 14 days were observed. In repeated dose study, the product was orally administered to Sprague Dawley rats of both sexes. Animals received 50, 250 and 500 mg/kg/day of the product for 90 days. At the end, animals were sacrificed and samples were done for hematological and biochemical analysis, organ weighs and histopathological examination. Genotoxicity potential of Sacha Inchi powder was evaluated through micronucleus test in mice. Negative controls received the vehicle (carboxymethyl cellulose, 0.5% used. Results: No morbidity or mortality at 2000 mg/kg of the product were found. Sacha Inchi powder oral administration during 90 days to rats did not lead to death, body weight gain, food consumption, or adverse events. No significant changes on hematological or biochemical parameters, organ weights or histopathological findings were observed. Induction of micronucleus formation attributable to the product was not found in mice. Conclusions: No toxicity effects after oral acute exposure of Sacha Inchi power to rats and mice were observed. Neither toxicity attributable to oral doses of the product up to 500 mg/kg during 90 days to rats were found. Results suggested Sacha Inchi powder does not have genotoxicity potential under our experimental conditions.

Toxicity of chromium (VI) to two mussels and an amphipod in water-only exposures with or without a co-stressor of elevated temperature, zinc, or nitrate

Science.gov (United States)

Wang, Ning; Kunz, James L.; Ivey, Chris D.; Ingersoll, Christopher G.; Barnhart, M. Christopher; Glidewell, Elizabeth A.

2017-01-01

The objectives of the present study were to develop methods for propagating western pearlshell (Margaritifera falcata) for laboratory toxicity testing and evaluate acute and chronic toxicity of chromium VI [Cr(VI)] to the pearlshell and a commonly tested mussel (fatmucket, Lampsilis siliquoidea at 20 °C or in association with a co-stressor of elevated temperature (27 °C), zinc (50 µg Zn/L), or nitrate (35 mg NO3/L). A commonly tested invertebrate (amphipod, Hyalella azteca) also was tested in chronic exposures. Newly transformed pearlshell (~1 week old) were successfully cultured and tested in acute 96 h Cr exposures (control survival 100%). However, the grow-out of juveniles in culture for chronic toxicity testing was less successful and chronic 28-day Cr toxicity tests started with 4 month-old pearlshell failed due to low control survival (39–68%). Acute median effect concentration (EC50) for the pearlshell (919 µg Cr/L) and fatmucket (456 µg Cr/L) tested at 20 °C without a co-stressor decreased by a factor of > 2 at elevated temperature but did not decrease at elevated Zn or elevated NO3. Chronic 28-day Cr tests were completed successfully with the fatmucket and amphipod (control survival 83–98%). Chronic maximum acceptable toxicant concentration (MATC) for fatmucket at 20 °C (26 µg Cr/L) decreased by a factor of 2 at elevated temperature or NO3 but did not decrease at elevated Zn. However, chronic MATC for amphipod at 20 °C (13 µg Cr/L) did not decrease at elevated temperature, Zn, or NO3. Acute EC50s for both mussels tested with or without a co-stressor were above the final acute value used to derive United States Environmental Protection Agency acute water quality criterion (WQC) for Cr(VI); however, chronic MATCs for fatmucket at elevated temperature or NO3 and chronic MATCs for the amphipod at 20 °C with or without elevated Zn or NO3 were about equal to the chronic WQC. The results indicate that (1) the elevated temperature

Evaluation of Daphnia ambigua for Routine Aquatic Toxicity Testing at the Savannah River Site

International Nuclear Information System (INIS)

Specht, W.L.; Harmon, S.M.

1997-09-01

that the life-cycle characteristics of this species were conducive to traditional acute and chronic aquatic toxicity test methods. Acute toxicity tests showed that when comparing LC50 values for C. dubia and D. ambigua, D. ambigua was less sensitive to some toxicants (sodium chloride, copper sulfate, and sodium lauryl sulfate) while more sensitive to others (chlorpyrifos). Results of chronic tests with copper sulfate and sodium chloride resulted in the same NOEC/LOEC values for both species. When exposed to unaltered SRS stream water, C. dubia demonstrated a 'toxic' response for two of the three streams tested, while reproduction for D. ambigua was higher in all stream samples. Acute toxicity tests with sodium chloride in stream water, generally followed the sensitivity trend noted in tests conducted with regular laboratory water

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

Science.gov (United States)

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

2018-01-01

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

Hyperhomocyst(e)inaemia in children with chronic renal failure

NARCIS (Netherlands)

Lilien, M.; Duran, M.; van Hoeck, K.; Poll-The, B. T.; Schröder, C.

1999-01-01

BACKGROUND: Hyperhomocyst(e)inaemia has been identified as a significant risk factor for the occurrence of atherosclerosis in adults with chronic renal failure. Because of its presumed direct toxic effect on the vascular wall, long-standing hyperhomocyst(e)inaemia in children with chronic renal

The use of bioassays to assess the toxicity of sediment in an acid ...

African Journals Online (AJOL)

Exposure of river sediment from 7 sampling sites to these bioassays provided an eco-toxicological estimation of the acute toxicity and chronic toxicity emanating from the contaminated sediments. Physico-chemical analyses revealed higher levels of sediment contamination closer to the mine. The bioassays displayed a ...

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-10-15

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

Etiologies of chronic liver disease in children

Directory of Open Access Journals (Sweden)

Farahmand F

2001-11-01

Full Text Available Chronic Liver diseases in children is the result of many different diseases including: metabolic, genetic, infectious, toxic and idiopathic causes. This was a case series study on 133 infants and children with age range 6 month to 12 years old, who presented clinically with manifestation of chronic liver disease and were admitted to Children Hospital Medical Center from year 1999 to 2000. In this study, 32 (24.5 percent patients had autoimmune chronic hepatitis, 15 (11.3 percent Glycogen storage diseases, 12 (9 percent extrahepatic biliary atresia, 11 (8.2 percent willson disease, 10 (7.5 percent cryptogenic cirrhosis, 6 (4.5 percent chronic hepatitis C, 5 (3.8 percen chronic hepatitic B, 5 (3.8 percent galactosemia 3 (2.25 percent congenital hepatic fibrosis, 3 (3.8 percent histiocytosis X, 3 (2.25 percent sclerosing cholangitis, 2 (1.5 percent byler’s disease 2 (1.5 percent primary tuberculosis, 1 (0.75 percent choledocalcyst, 1 (0.75 percent Alagyle syndrome. According to our data, chronic liver disease should be considered in infants and children. In our study, the most common causes are found to be: metabolic and genetic diseases (37.5 percent, chronic autoimmune hepatitis (24 percent and biliary disorders (14 percent, that encompass 86 percent of the patients.

Chronic toxicology of cannabis.

Science.gov (United States)

Reece, Albert Stuart

2009-07-01

Cannabis is the most widely used illicit drug worldwide. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. This review focuses on the latter. A systematic review of Medline, PubMed, PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana," "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198 papers. This list was screened by hand, and papers describing mechanisms and those published in more recent years were chosen preferentially for inclusion in this review. There is evidence of psychiatric, respiratory, cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state. Respiratory conditions linked with cannabis include reduced lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a dose-dependent manner with elevated rates of myocardial infarction and cardiac arrythmias. It is known to affect bone metabolism and also has teratogenic effects on the developing brain following perinatal exposure. Cannabis has been linked to cancers at eight sites, including children after in utero maternal exposure, and multiple molecular pathways to oncogenesis exist. Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all of which depend upon dose and duration of use.

The evaluation of a modified technique of Total Body Irradiation in respect of treatment results and toxicity

International Nuclear Information System (INIS)

Skowronska-Gardas, A.; Dabrowski, R.; Pedziwiatr, K.

2006-01-01

Total body irradiation (TBI) is a well established part of the conditioning regimen prior to bone marrow transplantation (BMT). Numerous different techniques are used and every center elaborates own solutions. The aim of our study to present the method of TBI developed in our department, and to discuss the results of treatment with respect of early and late toxicity. Between 11.2000 and 08.2004, 23 patients were with fractionated TBI at the Department of Radiotherapy of the M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology in Warsaw (MSCMCC). Conditioning chemotherapy and BMT were performed in different hematological departments. All patients were irradiated with a total midline dose of 12 Gy in 6 fractions over 3 consecutive days. Doses to the lung did not exceed 11 Gy. The TBI method used in our department was evaluated over a few years. The following modifications have been introduced to the previously applied technique: change of photon energy 6 MV to 15 MV; increase of lung dose from 9 Gy to 11 Gy; the use of an individual bolus as a lung compensator in lateral fields; more frequent boost irradiation of the mediastinum and legs with small fields; calculations of Monitor Units based on dosimetric data. Boost irradiation of chest wall with electrons been abandoned. Median follow up was 12 months. Up till now, 17/23 patients are alive, of these 16 with no relapse. Immediate toxicity was low. Early complications were observed during the first 6 months after BMT in 11 patients. In the case of 4 patients these complications were fatal. Late complications were observed in 10 patients, including chronic GVHD and hormone disturbance. Only one patient had developed the first symptoms of cataract. In one case Lhermitte's syndrome was observed. One patient died due to liver insufficiency. The results of treatment and the complications rates in patients treated with TBI at our department are consistent with those published in literature. We conclude that

Refinery water (intake and effluent) quality: Update of 1970s with 1990s toxicity testing

International Nuclear Information System (INIS)

Chapman, P.M.; Paine, M.D.; Moran, T.; Kierstead, T.

1994-01-01

The quality of two separate refinery intake waters and effluents was investigated: Petro-Canada (Oakville) and Novacor (Corunna Operations). This study comprised eight different test organized and 22 different toxicity end points, was built on and complemented pioneering 1970s work at the Petro-Canada refinery, and was designed to (a) determine any changes in effluent quality, (b) determine any previously unsuspected effluent toxicity, and (c) determine any potential for chronic toxicity in the effluent. Although Petro-Canada has steadily reduced contaminants in its effluent since the earlier study, toxicity has not changed and no new toxic effects were identified. Effect thresholds for the most sensitive animal species (Daphnia pulex) were 1 to 10% effluent in both studies. The Novacor effluent had lesser effects on biota than the Petro-Canada effluent. Intake waters demonstrated toxicity in some tests. Chronic effects on invertebrates and fish in receiving waters are predicted not to occur in the Novacor effluent is diluted 10- to 20-fold and the Petro-Canada effluent is diluted 50- to 100-fold

Effects of 60Co gamma radiation on toxicity and hemorrhagic, myonecrotic, and edema-forming activities of Cerastes cerastes venom

International Nuclear Information System (INIS)

Abib, H.; Laraba-Djebari, F.

2003-01-01

Antisera are used as effective antidotes against the local effects of snake bites. To improve antisera production and extend the life of surrogates used to produce antibodies, the chronic effects of venom toxicity must be reduced. The present study evaluated the effectiveness of gamma irradiation to reduce the local effects associated with viperid snake bites by evaluating in NMRI mice the toxicity and edematic, hemorrhagic, and myonecrotic activities of native and irradiated Cerastes cerastes venoms. These results indicated that the toxicity of irradiated venoms (1 and 2 kGy) decreased as compared with that of native venom. The edematic and hemorrhagic activities were also reduced in the detoxified samples, particularly with the 2-kGy radiation dose. Furthermore, the creatine phosphokinase (CPK) activity was significantly increased in the serum and decreased in the myocardium after envenomation with native venom, but no significant enzymatic changes were observed in mice envenomated with irradiated venom. Histopathologic evaluation showed that native venom caused severe degenerative changes in the myocardium. In the case of 2-kGy-irradiated venom, no tissue alterations were observed. These results indicate that irradiation of venom with a 2-kGy dose may offer an effective method for reducing the chronic toxic effects of venom in immunized animals. (author)

Toxicity of methanol to fish, crustacean, oligochaete worm, and aquatic ecosystem.

Science.gov (United States)

Kaviraj, A; Bhunia, F; Saha, N C

2004-01-01

Static renewal bioassays were conducted in the laboratory and in outdoor artificial enclosures to evaluate toxic effects of methanol to one teleost fish and two aquatic invertebrates and to limnological variables of aquatic ecosystem. Ninety-six-hour acute toxicity tests revealed cladoceran crustacea Moina micrura as the most sensitive to methanol (LC50, 4.82 g/L), followed by freshwater teleost Oreochromis mossambicus (LC50, 15.32 g/L) and oligochaete worm Branchiura sowerbyi (LC50, 54.89 g/L). The fish, when exposed to lethal concentrations of methanol, showed difficulties in respiration and swimming. The oligochaete body wrinkled and fragmented under lethal exposure of methanol. Effects of five sublethal concentrations of methanol (0, 23.75, 47.49, 736.10, and 1527.60 mg/L) on the feeding rate of the fish and on its growth and reproduction were evaluated by separate bioassays. Ninety-six-hour bioassays in the laboratory showed significant reduction in the appetite of fish when exposed to 736.10 mg/L or higher concentrations of methanol. Chronic toxicity bioassays (90 days) in outdoor enclosures showed a reduction in growth, maturity index and fecundity of fish at 47.49 mg/L or higher concentrations of methanol. Primary productivity, phytoplankton population, and alkalinity of water were also reduced at these concentrations. Chronic exposure to 1527.60 mg/L methanol resulted in damages of the epithelium of primary and secondary gill lamellae of the fish. The results revealed 23.75 mg/L as the no-observed-effect concentration (NOEC) of methanol to freshwater aquatic ecosystem.

Successful and Safe Treatment of Chronic Spontaneous Urticaria with Omalizumab in a Woman during Two Consecutive Pregnancies

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Misbah Nasheela Ghazanfar

2015-01-01

Full Text Available Chronic spontaneous urticaria is an itching skin disease characterised by wheals, angioedema, or both present for more than six weeks. Omalizumab is a humanized anti-IgE monoclonal antibody recently approved for treatment of chronic urticaria. Several randomised controlled trials have investigated the safety, tolerability, and efficacy of omalizumab for chronic urticaria. The safety of omalizumab in pregnancy is not known. We describe a female patient with chronic spontaneous urticaria who was treated with omalizumab continuously through two consecutive pregnancies with convincing results and no apparent toxicity.

Lambda-cyhalothrin toxicity in quails ( Cortunix japonica ...

African Journals Online (AJOL)

Lambda-cyhalothrin LCT is the active agent present in many insecticides used to control agricultural pest in Nigeria. Garlic contains a variety of effective compounds needed to increase the welfare of livestock. This study investigates the impact of chronic toxicity of the natural pyrethrin (LCT) on wildlife sentinels and the ...

Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex

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Rui Feng

2018-03-01

Full Text Available Nattokinase (NK, which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK, nattokinase-tauroursodeoxycholate (NK-TUDCA complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state, tail injury, and the body weight of mice, it was found that the NK-TUDCA complex (NK: 10 kIU/ml; TUDCA: 10 mg/ml; pH 5.0 had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NK-TUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK. Keywords: Nattokinase, Tauroursodeoxycholate, Complex, Toxicity test, In vitro thrombolytic test

Results of Toxicity Studies Conducted on Outfall X-08 and Its Contributing Waste Streams, November 1999 - June 2000

International Nuclear Information System (INIS)

Specht, W.L.

2000-01-01

This interim report summarizes the results of toxicity tests, Toxicity Identification Evaluations, and chemical analyses that have been conducted on SRS's NPDES Outfall X-08 and its contributing waste streams between November 1999 and June 2000

Results of Toxicity Identification Evaluations (TIE'S) conducted on the A-01 outfall and its contributory waste streams, July 1996 - February 1997

International Nuclear Information System (INIS)

Specht, W.L.

1997-03-01

Toxicity tests were conducted at nine locations during the summer of 1996. The results indicated that A-01B, A-01C, A-03, A-04, A-05 and A-01 were toxic to the test species, Ceriodaphnia dubia, while A-01A, A-06, and WE-01 were not toxic. Beginning in August 1996, Toxicity Identification Evaluations (TIE's) were initiated on all toxic outfalls in order to identify the toxicants responsible for the observed toxicity. A complete TIE was performed on A-01 because it is the regulatory compliance point for all of the combined waste streams that were tested. Only the portions of a TIE that are related to metal and chlorine toxicity were performed on the remaining locations because existing data indicated that metals and chlorine were present in potentially toxic quantities at these locations, and there was no evidence that other toxicants would be expected to be present in toxic amounts. The results of the TIE's indicate that metals are responsible for most of the toxicity at all of the outfalls that were toxic and that chlorine contributed to the toxicity at two of the outfalls. Specifically, the toxicity at A-01B, A-01C, and A-01 was due to copper; the toxicity at A-03 was due to primarily to copper, although zinc also contributed to the toxicity; the toxicity at A-04 was due primarily to copper, with residual chlorine and zinc contributing to the toxicity; and the toxicity at A-05 was due primarily to copper, with residual chlorine contributing to the toxicity. A-03 was the most toxic outfall, with 100% mortality occurring at concentrations as low as 12.5% effluent. A-03 was found to have concentrations of copper, lead, and zinc that exceeded EPA water quality criteria by approximately two orders of magnitude. The metal concentrations at A-01 and WE-01, which is located approximately 0.5 miles downstream from A-01 were similar. However, A-01 was toxic, while WE-01 was not

Design and Analysis of Chronic Aquatic Tests of Toxicity with Daphnia magna.

Science.gov (United States)

1981-12-01

surface waters. From that need evolved numerous standard toxicity tests. Aquatic toxicologists and biologists developed, refine,, and standard- ized many...experimental categorization summary sheets prepared by Dr. William van der Schalie, which is shown in Table I.I. 7 j-. " .’?, i...partial solution to this dilema can be obtained by studying the effects of the solvent alone. If the solvent by itself produces no toxic responses at

Frequency and impact of grade three or four toxicities of novel agents on outcomes of older patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma (alliance A151611).

Science.gov (United States)

Tallarico, Michael; Foster, Jared C; Seisler, Drew; Lafky, Jacqueline M; Hurria, Arti; Jatoi, Aminah; Cohen, Harvey J; Muss, Hyman B; Bartlett, Nancy; Cheson, Bruce D; Jung, Sin-Ho; Leonard, John P; Byrd, John C; Nabhan, Chadi

2018-04-16

Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004-2014. Toxicity was assessed per the NCI-CTCAE (version 3-5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. 1199 patients (409 age ≥ 65; 790 age four hematologic [odds ratio (OR) 1.70; p = 0.009: 95% CI (1.57-1.84)] and non-hematologic toxicities [OR 1.47; p = 0.022; 95% CI (1.39-1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p = 0.017; 95% CI (1.64-2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p = 0.006; 95% CI (2.25-4.39) for OS and 3.06; p = 0.011; 95% CI (2.10-4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed. CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL. Copyright © 2018 Elsevier Inc. All rights reserved.

Retinal toxicity associated with chronic exposure to hydroxychloroquine and its ocular screening. Review.

Science.gov (United States)

Geamănu Pancă, A; Popa-Cherecheanu, A; Marinescu, B; Geamănu, C D; Voinea, L M

2014-09-15

Hydroxychloroquine sulfate (HCQ, Plaquenil) is an analogue of chloroquine (CQ), an antimalarial agent, used for the treatment of systemic lupus erythematosus, rheumatoid arthritis and other autoimmune disorders. Its use has been associated with severe retinal toxicity, requiring a discontinuation of therapy. Because it presents potential secondary effects including irreversible maculopathy, knowledge of incidence, risk factors, drug toxicity and protocol screening of the patients it represents important data for the ophthalmologists. Thus, it is imperative that rheumatologists, medical internists and ophthalmologists are aware of the toxicity from hydroxychloroquine they should also be careful to minimize its occurrence and effects.

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

Energy Technology Data Exchange (ETDEWEB)

Ghilezan, Michel, E-mail: mghilezan@beaumont.edu [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States); Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy [Department of Radiation Oncology, William Beaumont Hospital and Rose Cancer Institute, Royal Oak, Michigan (United States)

2012-07-01

Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy Multiplication-Sign 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy Multiplication-Sign 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of {<=}12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable

High-Dose-Rate Brachytherapy as Monotherapy Delivered in Two Fractions Within One Day for Favorable/Intermediate-Risk Prostate Cancer: Preliminary Toxicity Data

International Nuclear Information System (INIS)

Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J. Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

2012-01-01

Purpose: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. Methods and Materials: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. Results: The median follow-up was 17 months (range, 6–40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. Conclusions: Favorable-risk prostate cancer patients treated with

[Chronic pancreatitis: new definition and perspectives.

Science.gov (United States)

Conti Bellocchi, Maria Cristina; De Pretis, Nicolò; Amodio, Antonio; Zerbi, Alessandro; Frulloni, Luca

2018-01-01

Chronic pancreatitis has been considered over the past years as a single disease, alcohol-induced and different from acute pancreatitis, in terms of etiology and prognosis. Actually, the introduction of a new concept of chronic pancreatitis, now considered as a fibroinflammatory process caused by multiple factors (toxic-metabolic, genetic, immunologic, obstructive), allow to better understand the pathogenesis of this complex disease. Furthermore, the discover of peculiar forms of chronic pancreatitis (autoimmune, paraduodenal, associated to gene mutations), different in term of clinical aspects, findings at imaging, prognosis and therapy, radically changed the concept of the disease. In this brief review, we described the impact of this new concept in the comprehension of pathogenesis, in the definition of peculiar forms of chronic pancreatitis, and in the clinical and therapeutic approach of chronic pancreatitis.

Functional Results in Arthroscopic Treatment in Patients with Chronic Lateral Elbow Pain.

Science.gov (United States)

Phorkhar, Termphong; Chanlalit, Cholawish

2015-11-01

Modern surgery as elbow arthroscopic surgery is an accepted operation due to benefit in precise intra-articular lesion detection and minimally invasive surgery. To report the functional results when using arthroscopic surgery to treat chronic lateral elbow pain. The data was collected from 25 patients with chronic lateral elbow pain that failed in non-operative treatment and treated with elbow arthroscopic surgery. Five patients were excluded from this study due to diagnosed as instability that needed the ligament reconstruction. The etiology of pain were grouped in to tennis elbow (4 pts), plica (9 pts), tennis elbow combined with plica (4 pts) and cartilage lesion (3 pts). Thai quick DASH questionnaire was used to evaluate the functional results by comparing pre and post operation score and calculated statistic results with paired t-test by level of significance p tennis elbow mean score was 74 and 33, in plica lesion mean score was 65 and 11, combined lesions mean score was 60 and 18 and cartilage lesion mean score was 60 and 20. Approaching chronic lateral elbow pain with arthroscopy can maintain the signficant improvement of functional result in midterm follow-up.

Surgical treatment of chronic idiopathic thrombocytopenic purpura: results in 107 cases

International Nuclear Information System (INIS)

Cola, B.; Tonielli, E.; Sacco, S.; Brulatti, M.; Franchini, A.

1986-01-01

Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP

The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy

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Christine Henri

2016-01-01

Full Text Available With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab, and multikinase inhibitors (sunitinib. The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy.

Toxicity of pentachlorophenol to aquatic organisms under naturally varying and controlled environmental conditions

Energy Technology Data Exchange (ETDEWEB)

Hedtke, S.F.; West, C.W.; Allen, K.N.; Norberg-King, T.J.; Mount, D.I.

1986-06-01

The toxicity of pentachlorophenol (PCP) was determined in the laboratory for 11 aquatic species. Tests were conducted seasonally in ambient Mississippi River water and under controlled conditions in Lake Superior water. Fifty-one acute toxicity tests were conducted, with LC50 values ranging from 85 micrograms/L for the white sucker Catastomus commersoni during the summer to greater than 7770 micrograms/L for the isopod Asellus racovitzai during the winter. The effect of PCP on growth and/or reproduction was determined for seven species. The most sensitive chronically exposed organisms were the cladoceran Ceriodaphnia reticulata and the snail Physa gyrina. The greatest variation in toxicity was due to species sensitivity. Within a given, season there was as much as a 40-fold difference in LC50 values between species. For any one species, the maximum variation in LC50 between seasons was approximately 14-fold. There were also substantial differences in acute-chronic relationships, with acute/chronic ratios ranging from greater than 37 for C. reticulata to 1 for Simocephalus vetulus. It is suggested that the composition of the aquatic community should be the most important consideration in estimating the potential environmental effects of PCP.

TOXICITY COMPARISON OF BIOSURFACTANTS AND SYNTHETIC SURFACTANTS USED IN OIL SPILL REMEDIATION TO TWO ESTUARINE SPECIES

Science.gov (United States)

The relative environmental toxicities of synthetic and biogenic surfactants used in oil spill remediation efforts are not well understood. Acute and chronic toxicities of three synthetic surfactants and three microbially produced surfactants were determined and compared in this s...

Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

Science.gov (United States)

Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

1999-12-01

The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary

Evaluation of the Safety of Imatinib Mesylate in 200 Iraqi Patients with Chronic Myeloid Leukemia in the Chronic Phase: Single-Center Study

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Bassam Francis Matti

2013-12-01

Full Text Available OBJECTIVE: Imatinib mesylate, a tyrosine kinase inhibitor, is presently the drug of choice for chronic myeloid leukemia (CML. During therapy, a few patients may develop hematological and non-hematological adverse effects. METHODS: The aim of this study was to evaluate the safety of imatinib therapy in patients with CML. Between December 2007 and October 2009 two hundred patients with CML in chronic phase were included in the study. Written informed consent was obtained from all patients prior to the start of the study. Imatinib was started at 400 mg orally daily. Patients were monitored carefully for any adverse effects. Complete blood count, liver, and renal function tests were done once in 2 weeks during the first month and on a monthly basis during follow-up. Toxicities that encountered were graded as per the National Cancer Institute common toxicity criteria version 2. Both hematologic and non-hematologic toxicities were managed with short interruptions of treatment and supportive measures, but the daily dose of imatinib was not reduced below 300 mg/day. RESULTS: Two hundred CML patients in chronic phase were included in this study; the male: female ratio was 0.7: 1 with mean age 39.06±13.21 years (ranged from 15-81 years. The study showed that the commonest hematological side effects were grade 2 anemia (12.5% followed by leukopenia (8% and thrombocytopenia (4%, while the most common non-hematological adverse effects were superficial edema and weight gain (51.5%, followed by musculoskeletal pain (35.5%, then gastro-intestinal symptoms (vomiting, diarrhea (19%. Fluid retention was the commonest side effect, which responded to low-dose diuretics. The drug was safe and well tolerated. There were no deaths due to toxicity. CONCLUSION: Imatinib mesylate a well-tolerated drug, and all undesirable effects could be ameliorated easily. The most common hematological and non-hematological side effects were anemia and fluid retention, respectively.

Application of TIE's in assessing toxicity associated with oil sands process waters

International Nuclear Information System (INIS)

MacKinnon, M.

1998-01-01

The hot water digestion process which separates bitumen from oil sands produces large volumes of process-affected waters which are extremely toxic to aquatic organisms. At Syncrude Canada's northeastern Alberta plant, the toxic waters are contained on the site and none are discharged. Organic acids, hydrocarbons and salts are leached into the tailings waters. A toxicity identification evaluation (TIE) test was used to confirm the main contributors to the acute toxicity in these waters. A battery bioassay approach as well as field and laboratory testing was used to understand the source, pathway and duration of the toxicity. Bioassays helped in developing ways in which to mitigate toxicity issues in both reclamation and operational waters. It was demonstrated that natural bioremediation of process-affected waters can reduce acute and chronic toxicity. The long term reclamation impacts of these waters has yet to be determined

An integrated omic analysis of hepatic alteration in medaka fish chronically exposed to cyanotoxins with possible mechanisms of reproductive toxicity.

Science.gov (United States)

Qiao, Qin; Le Manach, Séverine; Huet, Hélène; Duvernois-Berthet, Evelyne; Chaouch, Soraya; Duval, Charlotte; Sotton, Benoit; Ponger, Loïc; Marie, Arul; Mathéron, Lucrèce; Lennon, Sarah; Bolbach, Gérard; Djediat, Chakib; Bernard, Cécile; Edery, Marc; Marie, Benjamin

2016-12-01

Cyanobacterial blooms threaten human health as well as the population of other living organisms in the aquatic environment, particularly due to the production of natural toxic components, the cyanotoxin. So far, the most studied cyanotoxins are microcystins (MCs). In this study, the hepatic alterations at histological, proteome and transcriptome levels were evaluated in female and male medaka fish chronically exposed to 1 and 5 μg L -1 microcystin-LR (MC-LR) and to the extract of MC-producing Microcystis aeruginosa PCC 7820 (5 μg L -1 of equivalent MC-LR) by balneation for 28 days, aiming at enhancing our understanding of the potential reproductive toxicity of cyanotoxins in aquatic vertebrate models. Indeed, both MC and Microcystis extract adversely affect reproductive parameters including fecundity and egg hatchability. The liver of toxin treated female fish present glycogen storage loss and cellular damages. The quantitative proteomics analysis revealed that the quantities of 225 hepatic proteins are dysregulated. In particular, a notable decrease in protein quantities of vitellogenin and choriogenin was observed, which could explain the decrease in reproductive output. Liver transcriptome analysis through Illumina RNA-seq reveals that over 100-400 genes are differentially expressed under 5 μg L -1  MC-LR and Microcystis extract treatments, respectively. Ingenuity pathway analysis of the omic data attests that various metabolic pathways, such as energy production, protein biosynthesis and lipid metabolism, are disturbed by both MC-LR and the Microcystis extract, which could provoke the observed reproductive impairment. The transcriptomics analysis also constitutes the first report of the impairment of circadian rhythm-related gene induced by MCs. This study contributes to a better understanding of the potential consequences of chronic exposure of fish to environmental concentrations of cyanotoxins, suggesting that Microcystis extract could impact a

Multiple inorganic toxic substances contaminating the groundwater of Myingyan Township, Myanmar: arsenic, manganese, fluoride, iron, and uranium.

Science.gov (United States)

Bacquart, Thomas; Frisbie, Seth; Mitchell, Erika; Grigg, Laurie; Cole, Christopher; Small, Colleen; Sarkar, Bibudhendra

2015-06-01

In South Asia, the technological and societal shift from drinking surface water to groundwater has resulted in a great reduction of acute diseases due to water borne pathogens. However, arsenic and other naturally occurring inorganic toxic substances present in groundwater in the region have been linked to a variety of chronic diseases, including cancers, heart disease, and neurological problems. Due to the highly specific symptoms of chronic arsenic poisoning, arsenic was the first inorganic toxic substance to be noticed at unsafe levels in the groundwater of West Bengal, India and Bangladesh. Subsequently, other inorganic toxic substances, including manganese, uranium, and fluoride have been found at unsafe levels in groundwater in South Asia. While numerous drinking water wells throughout Myanmar have been tested for arsenic, relatively little is known about the concentrations of other inorganic toxic substances in Myanmar groundwater. In this study, we analyzed samples from 18 drinking water wells (12 in Myingyan City and 6 in nearby Tha Pyay Thar Village) and 2 locations in the Ayeyarwaddy River for arsenic, boron, barium, beryllium, cadmium, cobalt, chromium, copper, fluoride, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, uranium, vanadium, and zinc. Concentrations of arsenic, manganese, fluoride, iron, or uranium exceeded health-based reference values in most wells. In addition, any given well usually contained more than one toxic substance at unsafe concentrations. While water testing and well sharing could reduce health risks, none of the wells sampled provide water that is entirely safe with respect to inorganic toxic substances. It is imperative that users of these wells, and users of other wells that have not been tested for multiple inorganic toxic substances throughout the region, be informed of the need for drinking water testing and the health consequences of drinking water contaminated with inorganic toxic

Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.

Science.gov (United States)

Morimoto, Yasuo; Izumi, Hiroto; Yoshiura, Yukiko; Fujisawa, Yuri; Fujita, Katsuhide

Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.

Aquatic toxicity of airfield-pavement deicer materials and implications for airport runoff

Science.gov (United States)

Corsi, S.R.; Geis, S.W.; Bowman, G.; Failey, G.G.; Rutter, T.D.

2009-01-01

Concentrations of airfield-pavement deicer materials (PDM) in a study of airport runoff often exceeded levels of concern regarding aquatic toxicity. Toxicity tests on Vibrio fischeri, Pimephales promelas, Ceriodaphnia dubia, and Pseudokirchneriella subcapitata (commonly known as Selenastrum capricornutum) were performed with potassium acetate (K-Ac) PDM, sodium formate (Na-For) PDM, and with freezing- point depressants (K-Ac and Na-For). Results indicate that toxicity in PDM is driven by the freezing-point depressants in all tests except the Vibrio fisheri test for Na-For PDM which is influenced by an additive. Acute toxicity end points for different organisms ranged from 298 to 6560 mg/L (as acetate) for K-Ac PDM and from 1780 to 4130 mg/L (as formate) for Na- For PDM. Chronic toxicity end points ranged from 19.9 to 336 mg/L (as acetate) for K-Ac PDM and from 584 to 1670 mg/L (as formate) for Na-For PDM. Sample results from outfalls at General Mitchell International Airport in Milwaukee, Wl (GMIA) indicated that 40% of samples had concentrations greater than the aquatic-life benchmark for K-Ac PDM. K-Ac has replaced urea during the 1990s as the most widely used PDM at GMIA and in the United States. Results of ammonia samples from airport outfalls during periods when urea-based PDM was used at GMIA indicated that41% of samples had concentrations exceeding the U.S. Environmental Protection Agency (USEPA) 1 -h water-quality criterion. The USEPA 1-h water-quality criterion for chloride was exceeded in 68% of samples collected in the receiving stream, a result of road-salt runoff from urban influence near the airport. Results demonstrate that PDM must be considered to comprehensively evaluate the impact of chemical deicers on aquatic toxicity in water containing airport runoff. ?? 2009 American Chemical Society.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

Science.gov (United States)

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

Are laboratory derived toxicity results informative for field situations? Case study on earthworm populations contaminated with heavy metals

NARCIS (Netherlands)

Klok, T.C.; Thissen, J.

2009-01-01

The relevance of laboratory tests on toxicants for field situations is often disputed given that laboratory tests are conducted under, next to the toxicant stress, optimal conditions which are not expected in field situations. In this paper we confront the results of laboratory tests on growth,

Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

International Nuclear Information System (INIS)

Menkarios, Cathy; Fortin, Bernard; Lambert, Carole; Vigneault, Éric; Brochet, Nicolas; Nguyen, David HA; Bahary, Jean-Paul; Jolicoeur, Marjory; Beauchemin, Marie-Claude; Villeneuve, Hugo; Van Nguyen, Thu

2011-01-01

Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment. We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival. Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%. Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

Energy Technology Data Exchange (ETDEWEB)

Cheshchevik, V.T. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V. [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Reiter, R.J. [Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229–3900 (United States); Prokopchik, N.I. [Grodno State Medical University, Gorkogo - 80, 230015 Grodno (Belarus); Zavodnik, I.B., E-mail: zavodnik_il@mail.ru [Institute for Pharmacology and Biochemistry, National Academy of Sciences of Belarus, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus); Department of Biochemistry, Yanka Kupala Grodno State University, Len. Kom. Blvd. - 50, 230017 Grodno (Belarus)

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

Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity.

Science.gov (United States)

Kudryasheva, N S; Rozhko, T V

2015-04-01

The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1--absence of effects (stress recognition), 2--activation (adaptive response), and 3--inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhancement of parathion toxicity to quail by heat and cold exposure

Science.gov (United States)

Rattner, B.A.; Becker, J.M.; Nakatsugawa, T.

1987-01-01

Effects of ambient temperature on the acute oral toxicity of parathion were investigated in Japanese quail (Coturnix japonica) maintained at thermoneutral temperature (26.degree. C) or exposed to elevated (37.degree. C) or reduced (4.degree. C) temperatures commonly encountered by free-ranging wild birds. Based upon estimates of the median lethal dosage, there was up to a two-fold enhancement of parathion toxicity in birds chronically exposed to heat or cold. Twenty-four hours after administration of a low dosage (4 mg/kg body wt, po), there was markedly greater cholinesterase inhibition in surviving heat-exposed quail compared with those reared at 26.degree. C (e.g., brain acetylcholinesterase depression of 42% versus 12%). There were no differences in hepatic activities of parathion oxidase, paraoxonase, or paraoxon deethylase which could account for greater toxicity to chronically heat-exposed birds. In contrast, 4 mg parathion/kg wt elicited less plasma cholinesterase inhibition in cold-exposed quail compared to thermoneutral controls (e.g., birds is substantially influenced by environmental temperature.

[Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection].

Science.gov (United States)

Aguirrebengoa, Koldo

2014-11-01

Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Acute and Sub-Chronic Toxicity Potential Effects of Alchornea ...

African Journals Online (AJOL)

The open field test showed that sub-chronic administration increased rearing behavior significantly at the dose of 250 mg/kg/28 days but had no effect on grooming. In conclusion, the ethanolic extract has no toxicological effect as observed on hematological, biochemical and histopathological parameters even at the ...

Oral ketamine for children with chronic pain: a pilot phase 1 study

Science.gov (United States)

Bredlau, Amy-Lee; McDermott, Michael P.; Adams, Heather; Dworkin, Robert H; Venuto, Charles; Fisher, Susan; Dolan, James G; Korones, David N

2013-01-01

Objective To assess whether oral ketamine aids is is safe at higher dosages for sedating children and whether it may be an option for control of chronic pain in children. Study design A prospective study was performed on 12 children with chronic pain to identify the maximum tolerated dosage of oral ketamine. Participants were given 14 days of oral ketamine, three times daily, at dosages ranging from 0.25–1.5 mg/kg/dose. Participants were assessed for toxicity and for pain severity at baseline and on day 14 of treatment. Results Two participants, both treated at 1.5 mg/kg/dose, experienced dose-limiting toxicities (sedation and anorexia). One participant, treated at 1 mg/kg/dose, opted to stop ketamine treatment due to new pain on treatment. Nine participants completed their course of ketamine treatment. Of these 12 children, 5 experienced improvement in their pain scores, two with complete resolution of pain, lasting for more than 4 weeks off ketamine treatment. Conclusion Oral ketamine at dosages of 0.25–1 mg/kg/dose appears to be safe when given for 14 days to children with chronic pain. PMID:23403253

Bringing in vitro analysis closer to in vivo: Studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling.

Science.gov (United States)

Verheijen, Marcha; Schrooders, Yannick; Gmuender, Hans; Nudischer, Ramona; Clayton, Olivia; Hynes, James; Niederer, Steven; Cordes, Henrik; Kuepfer, Lars; Kleinjans, Jos; Caiment, Florian

2018-05-24

Doxorubicin (DOX) is a chemotherapeutic agent of which the medical use is limited due to cardiotoxicity. While acute cardiotoxicity is reversible, chronic cardiotoxicity is persistent or progressive, dose-dependent and irreversible. While DOX mechanisms of action are not fully understood yet, 3 toxicity processes are known to occur in vivo: cardiomyocyte dysfunction, mitochondrial dysfunction and cell death. We present an in vitro experimental design aimed at detecting DOX-induced cardiotoxicity by obtaining a global view of the induced molecular mechanisms through RNA-sequencing. To better reflect the in vivo situation, human 3D cardiac microtissues were exposed to physiologically-based pharmacokinetic (PBPK) relevant doses of DOX for 2 weeks. We analysed a therapeutic and a toxic dosing profile. Transcriptomics analysis revealed significant gene expression changes in pathways related to "striated muscle contraction" and "respiratory electron transport", thus suggesting mitochondrial dysfunction as an underlying mechanism for cardiotoxicity. Furthermore, expression changes in mitochondrial processes differed significantly between the doses. Therapeutic dose reflects processes resembling the phenotype of delayed chronic cardiotoxicity, while toxic doses resembled acute cardiotoxicity. Overall, these results demonstrate the capability of our innovative in vitro approach to detect the three known mechanisms of DOX leading to toxicity, thus suggesting its potential relevance for reflecting the patient situation. Our study also demonstrated the importance of applying physiologically relevant doses during toxicological research, since mechanisms of acute and chronic toxicity differ. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chronic Cough in Otorhinolaryngologic Routine

Directory of Open Access Journals (Sweden)

Palheta Neto, Francisco Xavier

2011-04-01

Full Text Available Introduction: The chronic cough is sometimes manifested as an imprecise symptom, but of great importance for both the diagnosis and the prognosis. In an otorhinolaryngologic approach, several illnesses that can occur with it can be numbered, including 2 of the 3 main causes of chronic cough. Objective: To identify the main otorhinolaryngologic diseases showing the chronic cough as one of their manifestations. Method: A literature's revision was performed in several scientific articles, specialized books and consultation in Birene and Scielo databases. Literature's revision: cough production in the upper airways is usually associated with an inflammatory reaction by stimulating sensitive receptors of these areas or by mechanic stimulus. The main cause of the chronic cough in the otorhinolaryngology day-to-day is the post-nasal drip, gathering together by itself 02 of the most common diseases: rhinitis and sinusitis. Laryngitis as a result of gastroesophageal reflux (GER stands out in the index of chronic cough etiology, but it is not as severe as GER . Neoplasias are also somewhat frequent causes of cough, and the difficulty in diagnosing the cough cause is common in this disease group. Motility disorder, laryngeal irritation persistence, parasitic disease and injuries by inhalation of toxic products were also found as a cause of cough for longer than 03 months. Conclusion:Chronic cough is a frequent and important finding in otorhinolaryngology and cannot be underestimated, and a careful anamnesis is the best way to determine the etiology and perform a correct treatment for the patient's disease.

Mapping the extent and relative toxicity of sediments, Winter Quarters Bay, Antarctica

International Nuclear Information System (INIS)

Crockett, A.; White, G.; Huynh, H.

1995-01-01

McMurdo Station was established in the mid 1950s and is the largest research station in Antarctica. In earlier days, wastes were dumped on the steep shores of Winter Quarters Bay, dosed with up to 19,000 L of diesel or jet fuel and ignited. Along with periodic fuel spills, and the discharge of raw sewage the Bay became littered with trash and contaminated with elevated levels of metals, PCBs and petroleum hydrocarbons. The original benthic community was essentially totally replaced with more opportunistic species. In 1993, a study was initiated to map the distribution of PCB and hydrocarbon contamination as well as determine sediment pore water toxicity. Sediments were collected from over forty locations with an Ekman dredge after drilling through about 210 cm of ice. Maps of sediment particle size distribution, percent organic carbon, total PCBs, total petroleum hydrocarbons, etc. were developed. Potential toxicity was mapped by normalizing the data to 1 percent organic carbon and comparing the data with various sediment quality criteria. While onsite sediment pore water toxicity tests showed essentially no impacts, the new Microtox trademark chronic bioassay on both pore water and solvent extra showed considerable toxic effects. This paper compares the relative levels of contamination, with sediment quality criteria and toxicity as determined by a chronic microbial bioassays

Toxicity of tritium

International Nuclear Information System (INIS)

Dobson, R.L.

1979-01-01

Among radionuclides of importance in atomic energy, 3 H has relatively low toxicity. The main health and environmental worry is the possibility that significant biological effects may follow from protracted exposure to low concentrations in water. To examine this possible hazard and measure toxicity at low tritium concentrations, chronic exposure studies were done on mice and monkeys. During vulnerable developmental periods animals were exposed to 3 HOH, and mice were exposed also to 60 Co gamma irradiation and energy-related chemical agents. The biological endpoint measured was the irreversible loss of female germ cells. Effects from tritium were observed at surprisingly low concentrations where 3 H was found more damaging than previously thought. Comparisons between tritium and gamma radiation showed the relative biological effectiveness (RBE) to be greater than 1 and to reach approximately 3 at very low exposures. For perspective, other comparisons were made: between radiation and chemical agents, which revealed parallels in action on germ cells, and between pre- and postnatal exposure, which warn of possible special hazard to the fetus from both classes of energy-related byproducts

Chronic ethanol or nicotine treatment results in partial cross-tolerance between these agents.

Science.gov (United States)

Burch, J B; de Fiebre, C M; Marks, M J; Collins, A C

1988-01-01

Female DBA/2Ibg mice were treated chronically (21 days) with ethanol- or dextrin-containing liquid diets or infused chronically with nicotine (8 mg/kg/h) or saline for 10 days. The responses of these animals to challenge doses of ethanol (2.5 g/kg) or nicotine (1 or 2 mg/kg) were measured using a test battery consisting of respiration rate, acoustic startle response, Y-maze crosses and rears, heart rate and body temperature. Chronic ethanol-treated animals were tolerant to the effects elicited by a challenge dose of ethanol on four of the six measures and were cross-tolerant to nicotine's effects on the acoustic startle test. Chronic nicotine-treated animals were tolerant to nicotine's effects on five of the six measures and cross-tolerant to ethanol's effects on heart rate and body temperature. Thus, partial cross-tolerance between ethanol and nicotine exists. Chronic nicotine treatment resulted in significant increases in L-[3H]-nicotine binding in six of seven brain regions and in alpha-[125I]-bungarotoxin binding in three of seven brain regions. Chronic ethanol treatment failed to alter the binding of either ligand. Therefore, the cross-tolerance that develops between ethanol and nicotine is not totally dependent on alterations in the number of brain nicotinic receptors.

Toxicity limitation on radioactive liquid waste discharge at OPG Nuclear Stations

International Nuclear Information System (INIS)

Dobson, T.; Lovasic, Z.; Nicolaides, G.

2000-01-01

This paper describes the Municipal and Industrial Strategy for Abatement (MISA) regulation, which came into effect in 1995 in Ontario (Ontario Regulation 215/95 under the Environmental Protection Act). This imposed additional limitations on liquid discharges from power generating stations. The MISA regulation has divided discharges into non-event and event streams, which have to be monitored for the prescribed parameters and for toxicity. Radioactive Waste Management Systems fall into the category of non-event streams. Standard toxicity testing involves monitoring lethality of Daphnia Magna and Rainbow trout in the effluent. The new legislation has imposed a need to address several issues: acute toxicity, complying with the specific limits prescribed by the regulation and, in the long run chronic toxicity

[Treatment and results of therapy in chronic idiopathic thrombocytopenic purpura].

Science.gov (United States)

Tasić, J; Milenović, M; Drasković, S; Vukicević, T; Macukanović, L; Kitić, Lj; Bakić, M

1994-01-01

Basic principles in the therapy of chronic idiopathic thrombocytopenic purpura are glucocorticoides and splenectomy. Other measures: Intravenous high doses gamma globulin therapy, attenuated androgenes, immunosupresive drugs and plasmaferesis are less effective. During the period of 1989-1992 we treated 34 patients. From 34 patients, 23 were women and 11 were men. We treated patients primarily by prednisolon approximaly for 2 - 4 weeks. Rarely we use doses of 3 mg/kg per day for short periods of time (5 to 10 days) or "pulse therapy" of 500 mg per day. Those doses may be effective in elevating platelet count if the response is poor. If response occurs, high dosages of steroides should be tareped to determine the amount that will maintain the platelet count in the range of 30x10(9)/l to 50x10(9)/l (to minimaze the toxic sade effects of steroides). If steroides are ineffective, we perform splenectomy. From 34 treated patients by glucocorticoides, in 16 we got remission and in 11 partial response. We discussed in detailes relationship duration of treatment with glucocorticoides and level of platelets, and also correlation duration of treatment with prognosis. From 6 splenectomized patients 3 were successful. In two patients we applied intravenous gamma globulin therapy and attenuated androgen successfuly. In one patients therapy with gamma globulin, immunosupresive drugs, androgen and other measures was ineffective. In one patients without splenectomy we administrated successfuly gamma globulin therapy and androgen for peroid of two years.

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

International Nuclear Information System (INIS)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang; Huang, Changjiang; Yang, Dongren

2016-01-01

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Chronic perfluorooctane sulfonate (PFOS) exposure induces hepatic steatosis in zebrafish

Energy Technology Data Exchange (ETDEWEB)

Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Yang, Dongren, E-mail: yangdongren@yahoo.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China)

2016-07-15

Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Hyperfractionated conformal radiotherapy in locally advanced prostate cancer: results of a dose escalation study

International Nuclear Information System (INIS)

Forman, Jeffrey D.; Duclos, Marie; Shamsa, Falah; Porter, Arthur T.; Orton, Colin

1996-01-01

Purpose: This study was initiated to assess the incidence of chronic complications and histologic and biochemical control following hyperfractionated conformal radiotherapy in patients with locally advanced prostate cancer. Methods and Materials: Between October 1991 and October 1994, 49 patients with locally advanced prostate cancer were entered on the first two dose levels of a prospective dose-escalation study using hyperfractionated three dimensional conformal radiotherapy. The first 25 patients received a minimum tumor dose of 78 Gy to the prostate and seminal vesicles in 6 weeks at 1.3 Gy, b.i.d. No increase in chronic toxicity compared with conventional radiotherapy was noted; therefore, an additional 24 patients were treated to a minimum tumor dose of 82.8 Gy to the prostate and seminal vesicles in 7 weeks at 1.15 Gy, b.i.d. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. Efficacy was assessed through scheduled postradiation prostate specific antigen values and ultrasound-guided biopsies. The median follow-up for the entire group was 20 months. Results: The hyperfractionated external radiation was well tolerated with minimal acute morbidity. At 30 months, the actuarial probability of Grade 2 gastrointestinal toxicity was 17%. At 30 months, the actuarial probability of Grade 2 genitourinary toxicity was 16%. There was no statistically significant difference between the two dose levels. No Grade 3 or 4 gastrointestinal or genitourinary toxicity was noted. At 12 months, 84% of patients had a prostate specific antigen ≤ 4; and 53%; ≤ 1 ng/ml. At 12 months, 71% of patients had post radiation biopsies that were either negative (55%) or showed a marked therapeutic effect (16%). Conclusion: The use of hyperfractionated conformal radiotherapy facilitated dose escalation with no increase in chronic toxicity compared to standard doses. The initial tumor response based on prostate specific antigen measurements and

Diuron exposure induces systemic and organ-specific toxicity following acute and sub-chronic exposure in male Wistar rats.

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Domingues, Alexandre; Barbisan, Luis Fernando; Martins, Priscila Raquel; Spinardi-Barbisan, Ana Lúcia Tozzi

2011-05-01

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substitute urea herbicide widely used on agricultural crops with potential mutagenic, teratogenic, reproductive and carcinogenic effects. Nonetheless, its toxic potential on the immune system needs a detailed assessment. Thus, in order to evaluate the adverse effect of this herbicide on lymphohematopoietic organs and macrophage activity, male Wistar rats were orally treated with Diuron at 125, 1250 and 2500 ppm for 14, 28 or 90 days. General signs of toxicity were observed in Diuron-treated groups (1250 and 2500 ppm), including reduced food intake and body weight gain, as well as higher relative weights for spleen, kidneys and liver (28 and 90-day toxicity studies) and elevated serum levels of ALT, albumin, total protein, creatinine and urea (28-day toxicity study). Diuron exposure caused a severe depletion of splenic white pulp compartments and cellularity, followed by a decreased number of CD4(+) T lymphocytes, increased extramedullary hematopoiesis and deposition of hemosiderin in red pulp. Despite alteration in macrophage spreading, the macrophagic activity was not significantly affected by the herbicide. Under these experimental conditions, the results suggest that Diuron exerts systemic and target-organ toxicity, mainly at higher concentration. Copyright © 2011 Elsevier B.V. All rights reserved.

Integration of Density Dependence and Concentration Response Models Provides an Ecologically Relevant Assessment of Populations Exposed to Toxicants

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The assessment of toxic exposure on wildlife populations involves the integration of organism level effects measured in toxicity tests (e.g., chronic life cycle) and population models. These modeling exercises typically ignore density dependence, primarily because information on ...

Toxicity and genotoxicity of the quaternary ammonium compound benzalkonium chloride (BAC) using Daphnia magna and Ceriodaphnia dubia as model systems

International Nuclear Information System (INIS)

Lavorgna, Margherita; Russo, Chiara; D'Abrosca, Brigida; Parrella, Alfredo; Isidori, Marina

2016-01-01

The toxicity and genotoxicity of the cationic surfactant benzalkonium chloride (BAC) were studied using Daphnia magna and Ceriodaphnia dubia as model systems. Acute and chronic toxicity testing were performed according to the international standard guidelines and the genotoxicity was detected through the comet assay on cells from whole organisms in vivo exposed. Acute effects occurred at concentrations in the order of tens of μg/L in D. magna and hundreds of μg/L in C. dubia. Chronic effects were found at one order of magnitude less than short-term effects maintaining the same difference in sensitivity between D. magna and C. dubia. BAC induced relevant DNA damage, in both cladocerans; the lowest adverse effect levels were 0.4 and 4 ng/L for D. magna and C. dubia, respectively. As these effective concentrations are far lower than BAC occurrence in surface waters (units of μg/L) a concerning environmental risk cannot be excluded. The findings of this study showed that D. magna and C. dubia, could be used as model organisms to detect acute and chronic toxicity as well as genotoxicity at the whole organism level. - Highlights: • Benzalkonium chloride chronic effect in C. dubia was found at dozens of μg/L. • The LOAEC detected by comet assay in D. magna is in the order of hundreds of pg/L. • D. magna and C. dubia are useful model organisms to detect toxicity and genotoxicity. - Benzalkonium chloride showed chronic toxicity and genotoxicity in Daphnia magna and Ceriodaphnia dubia at concentrations of environmental concern. Daphnids are useful model organisms.

Acute toxicity and sleep-wake EEG analysis of Stachtarpheta ...

African Journals Online (AJOL)

The effect of systemic administration of TASC on sleep architecture in rats was also evaluated in Sprague-Dawley rats that were chronically implanted with electrodes for electroencephalogram (EEG) and electromyogram (EMG) recording. The acute toxicity test revealed no lethal effect with doses of SCCR (up to 2000 ...

40 CFR 797.1930 - Mysid shrimp acute toxicity test.

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2010-07-01

... test organisms and eliminating loss of organisms in outflow water. (6) “Static system” means a test..., procedures, and mysids from the same population or culture container, except that none of the chemical is... in chronic toxicity tests should originate from laboratory cultures in order to ensure the...

Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

International Nuclear Information System (INIS)

Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

2007-01-01

Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

Imidacloprid toxicity impairs spatial memory of echolocation bats through neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas.

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Hsiao, Chun-Jen; Lin, Ching-Lung; Lin, Tian-Yu; Wang, Sheue-Er; Wu, Chung-Hsin

2016-04-13

It has been reported that the decimation of honey bees was because of pesticides of imidacloprid. The imidacloprid is a wildly used neonicotinoid insecticide. However, whether imidacloprid toxicity interferes with the spatial memory of echolocation bats is still unclear. Thus, we compared the spatial memory of Formosan leaf-nosed bats, Hipposideros terasensis, before and after chronic treatment with a low dose of imidacloprid. We observed that stereotyped flight patterns of echolocation bats that received chronic imidacloprid treatment were quite different from their originally learned paths. We further found that neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas of echolocation bats that received imidacloprid treatment was significantly enhanced in comparison with echolocation bats that received sham treatment. Thus, we suggest that imidacloprid toxicity may interfere with the spatial memory of echolocation bats through neural apoptosis in hippocampal CA1 and medial entorhinal cortex areas. The results provide direct evidence that pesticide toxicity causes a spatial memory disorder in echolocation bats. This implies that agricultural pesticides may pose severe threats to the survival of echolocation bats.

Toxicities of total-body irradiation for pediatric bone marrow transplantation

International Nuclear Information System (INIS)

Chou, Rachel H.; Wong, Garrett B.; Kramer, Joel H.; Wara, Diane W.; Matthay, Katherine K.; Crittenden, Mary R.; Swift, Patrick S.; Cowan, Morton J.; Wara, William M.

1996-01-01

Purpose: To determine the acute and late effects, including cognitive function, of total body irradiation (TBI) and chemotherapy for bone marrow transplant (BMT) in children with immunodeficiency or hematologic disorders. Methods and Materials: At UCSF, 15 children with immunodeficiency disorders and 58 children with leukemia received chemoradiotherapy between July 1982 and November 1993 and were evaluated for toxicity. Patients with severe combined immunodeficiency disorder (SCID) received 7 Gy TBI while leukemia patients received 12 Gy TBI. Results: Eight immunodeficient patients (53%) are alive at 4 months to 11 years posttransplant. Acute toxicity was limited and treatment well tolerated. Most patients developed mild nausea and vomiting, skin rash, or erythema. Transient fever/chills, oral mucositis, and alopecia were noted in approximately 50% of patients. Seventy-three percent of patients demonstrated acute liver dysfunction, but only four (27%) developed veno-occlusive disease. All children had decreased growth velocity but normal growth hormone levels. Other endocrinologic evaluations including adrenocorticotropic hormone (ACTH), cortisol, and thyroid hormones were normal. Only one evaluable girl had delayed puberty with late onset of secondary sexual characteristics. Neuropsychological testing demonstrated an intelligence quotient (IQ) reduction between the baseline and 1 year post-BMT, with some recovery at 3 years. Only one patient developed a clinically significant cataract. Thirteen percent of patients had chronic interstitial lung disease. Four children developed exostosis. Only 1 of the 15 children developed a second malignancy (acute myelogenous leukemia) at age 5, 51 months posttransplant for SCID. For patients with leukemia, similar toxicities were observed. Twenty-nine percent disease-free survival was noted with a mean follow-up of 4.7 years. Twenty-two percent had chronic interstitial lung disease and two patients were diagnosed with cataracts

Thyroid cancer in toxic and non-toxic multinodular goiter

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Cerci C

2007-01-01

Full Text Available Background : Many authors have claimed that hyperthyroidism protects against thyroid cancer and believed that the incidence of malignancy is lower in patients with toxic multinodular goiter (TMG than in those with non-toxic multinodular goiter. But in recent studies, it was reported that the incidence of malignancy with TMG is not as low as previously thought. Aim : To compare the thyroid cancer incidence in patients with toxic and non-toxic multinodular goiter. Settings and Design : Histology reports of patients treated surgically with a preoperative diagnosis of toxic and non-toxic multinodular goiter were reviewed to identify the thyroid cancer incidence. Patients having a history of neck irradiation or radioactive iodine therapy were excluded from the study. Materials and Methods : We reviewed 294 patients operated between 2001-2005 from toxic and non-toxic multinodular goiter. One hundred and twenty-four of them were toxic and 170 were non-toxic. Hyperthyroidism was diagnosed by elevated tri-iodothyroinine / thyroxine ratios and low thyroid-stimulating hormone with clinical signs and symptoms. All patients were evaluated with ultrasonography and scintigraphy and fine needle aspiration biopsy. Statistical Analysis Used : Significance of the various parameters was calculated by using ANOVA test. Results : The incidence of malignancy was 9% in the toxic and 10.58% in the non-toxic multinodular goiter group. Any significant difference in the incidence of cancer and tumor size between the two groups could not be detected. Conclusions : The incidence of malignancy in toxic multinodular goiter is not very low as thought earlier and is nearly the same in non-toxic multinodular goiter.

High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data.

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Ghilezan, Michel; Martinez, Alvaro; Gustason, Gary; Krauss, Daniel; Antonucci, J Vito; Chen, Peter; Fontanesi, James; Wallace, Michelle; Ye, Hong; Casey, Alyse; Sebastian, Evelyn; Kim, Leonard; Limbacher, Amy

2012-07-01

within 1 day have excellent tolerance with minimal acute and chronic toxicity. Longer follow-up is needed to confirm these encouraging early results. Copyright © 2012 Elsevier Inc. All rights reserved.

Aerobic Bioremediation of PAH Contaminated Soil Results in Increased Genotoxicity and Developmental Toxicity.

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Chibwe, Leah; Geier, Mitra C; Nakamura, Jun; Tanguay, Robert L; Aitken, Michael D; Simonich, Staci L Massey

2015-12-01

The formation of more polar and toxic polycyclic aromatic hydrocarbon (PAH) transformation products is one of the concerns associated with the bioremediation of PAH-contaminated soils. Soil contaminated with coal tar (prebioremediation) from a former manufactured gas plant (MGP) site was treated in a laboratory scale bioreactor (postbioremediation) and extracted using pressurized liquid extraction. The soil extracts were fractionated, based on polarity, and analyzed for 88 PAHs (unsubstituted, oxygenated, nitrated, and heterocyclic PAHs). The PAH concentrations in the soil tested, postbioremediation, were lower than their regulatory maximum allowable concentrations (MACs), with the exception of the higher molecular weight PAHs (BaA, BkF, BbF, BaP, and IcdP), most of which did not undergo significant biodegradation. The soil extract fractions were tested for genotoxicity using the DT40 chicken lymphocyte bioassay and developmental toxicity using the embryonic zebrafish (Danio rerio) bioassay. A statistically significant increase in genotoxicity was measured in the unfractionated soil extract, as well as in four polar soil extract fractions, postbioremediation (p toxicity was measured in one polar soil extract fraction, postbioremediation (p soil extract fractions in embryonic zebrafish, both pre- and postbioremediation. The increased toxicity measured postbioremediation is not likely due to the 88 PAHs measured in this study (including quinones), because most were not present in the toxic polar fractions and/or because their concentrations did not increase postbioremediation. However, the increased toxicity measured postbioremediation is likely due to hydroxylated and carboxylated transformation products of the 3- and 4-ring PAHs (PHE, 1MPHE, 2MPHE, PRY, BaA, and FLA) that were most degraded.

Standardized toxicity testing may underestimate ecotoxicity: Environmentally relevant food rations increase the toxicity of silver nanoparticles to Daphnia.

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Stevenson, Louise M; Krattenmaker, Katherine E; Johnson, Erica; Bowers, Alexandra J; Adeleye, Adeyemi S; McCauley, Edward; Nisbet, Roger M

2017-11-01

Daphnia in the natural environment experience fluctuations in algal food supply, with periods when algal populations bloom and seasons when Daphnia have very little algal food. Standardized chronic toxicity tests, used for ecological risk assessment, dictate that Daphnia must be fed up to 400 times more food than they would experience in the natural environment (outside of algal blooms) for a toxicity test to be valid. This disconnect can lead to underestimating the toxicity of a contaminant. We followed the growth, reproduction, and survival of Daphnia exposed to 75 and 200 µg/L silver nanoparticles (AgNPs) at 4 food rations for up to 99 d and found that AgNP exposure at low, environmentally relevant food rations increased the toxicity of AgNPs. Exposure to AgNP at low food rations decreased the survival and/or reproduction of individuals, with potential consequences for Daphnia populations (based on calculated specific population growth rates). We also found tentative evidence that a sublethal concentration of AgNPs (75 µg/L) caused Daphnia to alter energy allocation away from reproduction and toward survival and growth. The present findings emphasize the need to consider resource availability, and not just exposure, in the environment when estimating the effect of a toxicant. Environ Toxicol Chem 2017;36:3008-3018. © 2017 SETAC. © 2017 SETAC.

Neurological Disorders in a Murine Model of Chronic Renal Failure

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Jean-Marc Chillon

2014-01-01

Full Text Available Cardiovascular disease is highly prevalent in patients with chronic renal failure (CRF. However, data on the impact of CRF on the cerebral circulatory system are scarce—despite the fact that stroke is the third most common cause of cardiovascular death in people with CRF. In the present study, we examined the impact of CRF on behavior (anxiety, recognition and ischemic stroke severity in a well-defined murine model of CRF. We did not observe any significant increases between CRF mice and non-CRF mice in terms of anxiety. In contrast, CRF mice showed lower levels of anxiety in some tests. Recognition was not impaired (vs. controls after 6 weeks of CRF but was impaired after 10 weeks of CRF. Chronic renal failure enhances the severity of ischemic stroke, as evaluated by the infarct volume size in CRF mice after 34 weeks of CRF. Furthermore, neurological test results in non-CRF mice tended to improve in the days following ischemic stroke, whereas the results in CRF mice tended to worsen. In conclusion, we showed that a murine model of CRF is suitable for evaluating uremic toxicity and the associated neurological disorders. Our data confirm the role of uremic toxicity in the genesis of neurological abnormalities (other than anxiety.

Analyzing the capacity of the Daphnia magna and Pseudokirchneriella subcapitata bioavailability models to predict chronic zinc toxicity at high pH and low calcium concentrations and formulation of a generalized bioavailability model for D. magna.

Science.gov (United States)

Van Regenmortel, Tina; Berteloot, Olivier; Janssen, Colin R; De Schamphelaere, Karel A C

2017-10-01

Risk assessment in the European Union implements Zn bioavailability models to derive predicted-no-effect concentrations for Zn. These models are validated within certain boundaries (i.e., pH ≤ 8 and Ca concentrations ≥ 5mg/L), but a substantial fraction of the European surface waters falls outside these boundaries. Therefore, we evaluated whether the chronic Zn biotic ligand model (BLM) for Daphnia magna and the chronic bioavailability model for Pseudokirchneriella subcapitata could be extrapolated to pH > 8 and Ca concentrations model can accurately predict Zn toxicity for Ca concentrations down to 0.8 mg/L and pH values up to 8.5. Because the chronic Zn BLM for D. magna could not be extrapolated beyond its validity boundaries for pH, a generalized bioavailability model (gBAM) was developed. Of 4 gBAMs developed, we recommend the use of gBAM-D, which combines a log-linear relation between the 21-d median effective concentrations (expressed as free Zn 2+ ion activity) and pH, with more conventional BLM-type competition constants for Na, Ca, and Mg. This model is a first step in further improving the accuracy of chronic toxicity predictions of Zn as a function of water chemistry, which can decrease the uncertainty in implementing the bioavailability-based predicted-no-effect concentration in the risk assessment of high-pH and low-Ca concentration regions in Europe. Environ Toxicol Chem 2017;36:2781-2798. © 2017 SETAC. © 2017 SETAC.

Scenario-targeted toxicity assessment through multiple endpoint bioassays in a soil posing unacceptable environmental risk according to regulatory screening values.

Science.gov (United States)

Rodriguez-Ruiz, A; Etxebarria, J; Boatti, L; Marigómez, I

2015-09-01

Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

Science.gov (United States)

2017-01-01

The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD), calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD) hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates), persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment. PMID:28567415

Neurodevelopmental Disorders and Environmental Toxicants: Epigenetics as an Underlying Mechanism

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Nguyen Quoc Vuong Tran

2017-01-01

Full Text Available The increasing prevalence of neurodevelopmental disorders, especially autism spectrum disorders (ASD and attention deficit hyperactivity disorder (ADHD, calls for more research into the identification of etiologic and risk factors. The Developmental Origin of Health and Disease (DOHaD hypothesizes that the environment during fetal and childhood development affects the risk for many chronic diseases in later stages of life, including neurodevelopmental disorders. Epigenetics, a term describing mechanisms that cause changes in the chromosome state without affecting DNA sequences, is suggested to be the underlying mechanism, according to the DOHaD hypothesis. Moreover, many neurodevelopmental disorders are also related to epigenetic abnormalities. Experimental and epidemiological studies suggest that exposure to prenatal environmental toxicants is associated with neurodevelopmental disorders. In addition, there is also evidence that environmental toxicants can result in epigenetic alterations, notably DNA methylation. In this review, we first focus on the relationship between neurodevelopmental disorders and environmental toxicants, in particular maternal smoking, plastic-derived chemicals (bisphenol A and phthalates, persistent organic pollutants, and heavy metals. We then review studies showing the epigenetic effects of those environmental factors in humans that may affect normal neurodevelopment.

Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

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Robin Mesnage

2014-01-01

Full Text Available Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3. Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone.

Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

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Spiroux de Vendômois, Joël; Séralini, Gilles-Eric

2014-01-01

Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazole, and prochloraz constitute, respectively, the active principles of 3 major herbicides, 3 insecticides, and 3 fungicides. We measured mitochondrial activities, membrane degradations, and caspases 3/7 activities. Fungicides were the most toxic from concentrations 300–600 times lower than agricultural dilutions, followed by herbicides and then insecticides, with very similar profiles in all cell types. Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested. Most importantly, 8 formulations out of 9 were up to one thousand times more toxic than their active principles. Our results challenge the relevance of the acceptable daily intake for pesticides because this norm is calculated from the toxicity of the active principle alone. Chronic tests on pesticides may not reflect relevant environmental exposures if only one ingredient of these mixtures is tested alone. PMID:24719846

Quality of life with well-differentiated thyroid cancer: treatment toxicities and their reduction.

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Mendoza, April; Shaffer, Brian; Karakla, Daniel; Mason, M Elizabeth; Elkins, David; Goffman, Thomas E

2004-02-01

Patients with well-differentiated thyroid cancer have a good prognosis but a significant chance for local recurrence. In the past, limited surgery with postoperative 131I only for extremely high-risk cases or recurrence was not uncommon. As more aggressive surgical and postoperative treatments appear to gain wider acceptance, toxicity and long-term morbidity become more important issues. Our goal is to present the experience of a single institution with emphasis on oral side effects related to 131I as well as acute and chronic symptoms related to this diagnosis and their impact on quality of life. Fifty-seven patients were followed for a median time of 19.3 months. All patients received therapeutic 131I (mean dose, 154.7 mCi) between January 1, 1996 and August 30, 2002. Fifty-four patients (94.7%) were alive at the time of analysis. Sixteen (28.1%) required a second treatment: any sign of persistence resulted in retreatment. Complaints with 131I treatment included altered taste, 26.3%; acute xerostomia, 21.1%; and acute sialoadenitis, 15.8%. Chronic xerostomia occurred in 6 (35.3%) of all patients who received multiple treatments. The incidence of chronic xerostomia was reduced to 1 of 11 (9.1%) with amifostine pretreatment. Other chronic side effects associated with this disease included fatigue 54.4%, weight gain of more than 6 months duration 24.6%, with 12 (27.9%) of those under 60 experiencing an average gain of 2.3 kg from initial diagnosis. Review of treatment-related symptoms prompted policies to reduce toxicity including amifostine pretreatment for 131I therapy and thyrotropin (synthetic TSH) use in place of iatrogenic hypothyroidism for thyroglobulin testing and scanning.

Bosutinib in the management of chronic myelogenous leukemia

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Keller-von Amsberg G

2013-05-01

Full Text Available Gunhild Keller-von Amsberg, Philippe SchafhausenDepartment of Hematology and Oncology and, Stem Cell Transplantation and Pulmonology Division, Oncological Center, University Hospital Hamburg-Eppendorf, Hamburg, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily dual Src and Abl kinase inhibitor, approved by the US Food and Drug Administration for the treatment of adults with chronic, accelerated, or blast-phase Philadelphia chromosome-positive chronic myelogenous leukemia who are intolerant of or resistant to first- or second-generation tyrosine kinase inhibitors. Bosutinib effectively overcomes the majority of imatinib-resistance-conferring BCR-ABL mutations except V299L and T315I. In the Bosutinib Efficacy and Safety in chronic myeloid LeukemiA (BELA trial, bosutinib attained a faster and deeper molecular response than imatinib in newly diagnosed chronic-phase chronic myelogenous leukemia patients. Treatment-emergent adverse events are usually very manageable. Low grade, mostly self-limiting diarrhea represents the most frequently observed toxicity of bosutinib. Anti-diarrheal drugs, antiemetic agents, and/or fluid replacement should be used to treat these patients. The improved hematological toxicity of bosutinib compared with other tyrosine kinase inhibitors has been ascribed to its minimal activity against platelet-derived growth factor receptor and KIT. In this review, we give an overview on the profile of bosutinib, the clinical potential and treatment-emergent adverse events.Keywords: CML, BCR-ABL, SRC/ABL kinase inhibitor, resistance-conferring mutation

Prevalence of chronic pancreatitis: Results of a primary care physician-based population study.

Science.gov (United States)

Capurso, Gabriele; Archibugi, Livia; Pasquali, Piera; Aceti, Alessandro; Balducci, Paolo; Bianchi, Patrizia; Buono, Francesco; Camerucci, Stefano; Cantarini, Rosanna; Centofanti, Sergio; Colantonio, Patrizia; Cremaschi, Riccarda; Crescenzi, Sergio; Di Mauro, Caterina; Di Renzi, Davide; Filabozzi, Andrea; Fiorillo, Alfonso; Giancaspro, Giuseppe; Giovannetti, Paola; Lanna, Giuseppe; Medori, Claudio; Merletti, Emilio; Nunnari, Enzo; Paris, Francesca; Pavone, Marco; Piacenti, Angela; Rossi, Almerindo; Scamuffa, Maria Cristina; Spinelli, Giovanni; Taborchi, Marco; Valente, Biagio; Villanova, Antonella; Chiriatti, Alberto; Delle Fave, Gianfranco

2017-05-01

Data on chronic pancreatitis prevalence are scanty and usually limited to hospital-based studies. Investigating chronic pancreatitis prevalence in primary care. Participating primary care physicians reported the prevalence of chronic pancreatitis among their registered patients, environmental factors and disease characteristics. The data were centrally reviewed and chronic pancreatitis cases defined according to M-ANNHEIM criteria for diagnosis and severity and TIGAR-O classification for etiology. Twenty-three primary care physicians participated in the study. According to their judgment, 51 of 36.401 patients had chronic pancreatitis. After reviewing each patient data, 11 turned out to have definite, 5 probable, 19 borderline and 16 uncertain disease. Prevalence was 30.2/100.000 for definite cases and 44.0/100.000 for definite plus probable cases. Of the 16 patients with definite/probable diagnosis, 8 were male, with mean age of 55.6 (±16.7). Four patients had alcoholic etiology, 5 post-acute/recurrent pancreatitis, 6 were deemed to be idiopathic. Four had pancreatic exocrine insufficiency, 10 were receiving pancreatic enzymes, and six had pain. Most patients had initial stage and non-severe disease. This is the first study investigating the prevalence of chronic pancreatitis in primary care. Results suggest that the prevalence in this context is higher than in hospital-based studies, with specific features, possibly representing an earlier disease stage. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chronic dietary toxicity of zinc oxide nanoparticles in common carp (Cyprinus carpio L.): Tissue accumulation and physiological responses.

Science.gov (United States)

Chupani, Latifeh; Niksirat, Hamid; Velíšek, Josef; Stará, Alžběta; Hradilová, Šárka; Kolařík, Jan; Panáček, Aleš; Zusková, Eliška

2018-01-01

Concerns regarding the potential toxic effects of zinc oxide nanoparticles (ZnO NPs) on aquatic organisms are growing due to the fact that NPs may be released into aquatic ecosystems. This study aimed to investigate the effects of dietary exposure to ZnO NPs on juvenile common carp (Cyprinus carpio). Fish were fed a spiked diets at doses 50 and 500mg of ZnO NPs per kg of feed for 6 weeks followed by a 2-week recovery period. Fish were sampled every 2 weeks for haematology trends, blood biochemistry measures, histology analyses, and determination of the accumulation of zinc in tissues. At the end of the exposure and post-exposure periods, fish were sampled for an assessment of lipid peroxidation levels. Dietborne ZnO NPs had no effects on haematology, blood biochemistry, and lipid peroxidation levels during the exposure period. After the recovery period, aspartate aminotransferase activity significantly (p < 0.05) increased and alanine transferase activity significantly (p < 0.05) decreased in the higher exposure group. The level of lipid peroxidation significantly (p < 0.05) decreased in liver of treated fish after 2 weeks post-exposure period. A histological examination revealed mild histopathological changes in kidneys during exposure. Our results did not show a significant increase of zinc content at the end of experiment in any of tested organs. However, chronic dietary exposure to ZnO NPs might affect kidney and liver function. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo assessment of toxicity and pharmacokinetics of methylglyoxal

International Nuclear Information System (INIS)

Ghosh, Manju; Talukdar, Dipa; Ghosh, Swapna; Bhattacharyya, Nivedita; Ray, Manju; Ray, Subhankar

2006-01-01

Previous in vivo studies from several laboratories had shown remarkable curative effect of methylglyoxal on cancer-bearing animals. In contrast, most of the recent in vitro studies have assigned a toxic role for methylglyoxal. The present study was initiated with the objective to resolve whether methylglyoxal is truly toxic in vivo and to reassess its therapeutic potential. Four species of animals, both rodent and non-rodent, were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests had been done with mouse and rat. These animals received 2, 1 and 0.3 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Chronic (treatment for around a month) toxicity test had been done with mouse, rat, rabbit and dog. Mouse, rat and dog received 1, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. Rabbit received 0.55, 0.3 and 0.1 g of methylglyoxal/kg of body weight in a day through oral, subcutaneous and intravenous routes respectively. It had been observed that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies were done with rats that were subjected to chronic toxicity tests. It had been observed that these animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. Studies on several biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal-treated mouse were performed. These studies indicated that methylglyoxal had no apparent deleterious effect on some vital organs of these animals. A detailed pharmacokinetic study was done with mouse after oral administration of methylglyoxal. The effect of methylglyoxal alone and in

Increased formic acid excretion and the development of kidney toxicity in rats following chronic dosing with trichloroethanol, a major metabolite of trichloroethylene

International Nuclear Information System (INIS)

Green, Trevor; Dow, Jacky; Foster, John

2003-01-01

The chronic toxicity of trichloroethanol, a major metabolite of trichloroethylene, has been assessed in male Fischer rats (60 per group) given trichloroethanol in drinking water at concentrations of 0, 0.5 and 1.0 g/l for 52 weeks. The rats excreted large amounts of formic acid in urine reaching a maximum after 12 weeks (∼65 mg/24 h at 1 g/l) and thereafter declining to reach an apparent steady state at 40 weeks (15-20 mg/24 h). Urine from treated rats was more acidic throughout the study and urinary methylmalonic acid and plasma N-methyltetrahydrofolate concentrations were increased, indicating an acidosis, vitamin B12 deficiency and impaired folate metabolism, respectively. The rats treated with trichloroethanol developed kidney damage over the duration of the study which was characterised by increased urinary NAG activity, protein excretion (from 4 weeks), increased basophilia, protein accumulation and tubular damage (from 12 to 40 weeks), increased cell replication (at week 28) and evidence in some rats of focal proliferation of abnormal tubules at 52 weeks. It was concluded that trichloroethanol, the major metabolite of trichloroethylene, induced nephrotoxicity in rats as a result of formic acid excretion and acidosis

Evaluation of distant results after lamivudine discontinuation in children with chronic hepatitis B.

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Lech Chyczewski

2010-08-01

Full Text Available The aim of this study was to estimate distant results after discontinuation of long term lamivudine treatment in children with chronic hepatitis B. Furthermore, the emergence of HBV polymerase gene variants in YMDD motif during therapy was examined. Additionally, the most commonly occurring type of mutation in the polymerase YMDD region were investigated. The study involved 27 HBeAg positive children with chronic hepatitis B. Children included to lamivudine therapy were previously treated without effects with interferon alpha.

Building a Foundation on Sand: The Demise of Leaders Resulting from Toxic Followership

Science.gov (United States)

2016-05-26

Toxic Followers, Prototype Theory, Mission Command, Operational Art, McClellan, Johnston, MacArthur, Powell, 16. SECURITY CLASSIFICATION OF: a. REPORT... Prototypical Differences, Toxicity, and Civil War Relationships. .........................................20 Analysis and Conclusion...West Point Cadets and College Students,” Journal of Political and Military Sociology, vol 29 (Summer 2001), 92-97. 4

Systemic toxicity of ropivacaine during ovine pregnancy.

Science.gov (United States)

Santos, A C; Arthur, G R; Pedersen, H; Morishima, H O; Finster, M; Covino, B G

1991-07-01

Ropivacaine is a new amide local anesthetic structurally related to bupivacaine and mepivacaine. Its potency and duration of action are similar to those of bupivacaine but its therapeutic index may be greater. Since pregnancy enhances the cardiotoxicity of bupivacaine, the current study was devised to compare the toxicity of ropivacaine in chronically instrumented nonpregnant and pregnant ewes during continuous intravenous infusion of the drug at the rate of 0.5 mg.kg-1.min-1. In all animals, symptoms of local anesthetic toxicity occurred in the usual order--convulsions, hypotension, apnea, and circulatory collapse. There were no significant differences between the two groups of animals in the doses and plasma concentrations of ropivacaine associated with each toxic manifestations. For example, circulatory collapse occurred at a mean dose of 11.3 +/- 1.1 mg.kg-1 in nonpregnant and 12.4 +/- 0.9 mg.kg-1 in pregnant animals, with corresponding plasma concentrations of 7.3 +/- 0.3 and 9.6 +/- 2.1 micrograms.ml-1 (P = not significant). Protein binding of ropivacaine in the concentration range associated with toxic manifestations was similar in sera obtained from nonpregnant and pregnant ewes. In conclusion, ovine pregnancy does not enhance the systemic toxicity of ropivacaine, possibly because of an absence of gestation-related increase in the availability of free drug.

76 FR 59142 - Guidance for Industry on Reproductive and Developmental Toxicities-Integrating Study Results To...

Science.gov (United States)

2011-09-23

... of study results to assess concerns about human reproductive and developmental toxicities. It does... assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic access to the guidance document. Submit electronic comments on the guidance to http://www.regulations.gov...

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

International Nuclear Information System (INIS)

Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

2012-01-01

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 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 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. Highlights: ► After 30-day chronic CCl 4 intoxication mitochondria displayed considerable changes. ► The functional parameters of mitochondria were similar to the control values. ► Melatonin + succinate + flavonoids prevented mitochondrial ultrastructure damage. ► The above complex enhanced regenerative processes in the liver.

The biomonitoring and bioremediation of toxic water resulting from municipal waste storage of Somârd, Sibiu county

OpenAIRE

Ioan C. Oprea; Dana Malschi; Liviu O. Muntean

2013-01-01

This paper presents information from the specialty literature and laboratory experimental results on biomonitoring, phytoextraction, biodegradation, and biotransformation of toxic water pollutants at the biotechnology laboratory of the Faculty of Environmental Science and Engineering. The study was conducted in laboratory micro tanks with contaminated water from the municipal landfill water storage pit with toxic bund of Somârd/Medias, Sibiu County, in order to research and develo...

[Acute onset pulmonary toxicity associated to amiodarone].

Science.gov (United States)

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.

Adenocarcinoma of the esophagogastric junction. Neoadjuvant radiochemotherapy and radical surgery. Early results and toxicity

Energy Technology Data Exchange (ETDEWEB)

Leibl, Bernhard J. [Klinikum Coburg (Germany). Dept. of Surgery; Coburg Cancer Center, Coburg (Germany); Vitz, Stephanie; Schaefer, Wolfgang; Alfrink, Martin; Grabenbauer, Gerhard G. [DiCura Coburg, Coburg (Germany). Dept. of Radiation Oncology; Coburg Cancer Center, Coburg (Germany); Geschwendtner, Andreas [Klinikum Coburg (Germany). Dept. of Pathology; Coburg Cancer Center, Coburg (Germany)

2011-04-15

Purpose: To retrospectively evaluate treatment results and toxicity following a combined approach consisting of neoadjuvant radiochemotherapy and radical surgery in advanced adenocarcinoma of the esophagus and gastroesophageal junction. Patients and Methods: Between 2005 and 2009, a total of 41 consecutive patients with newly diagnosed nonmetastatic adenocarcinoma of the esophagus and the esophagogastric junction were evaluated, of whom 23 received neoadjuvant radiochemo-therapy (RCT). A total dose of 50.4 Gy with 2 cycles of simultaneous cisplatin/5-fluorouracil (FU) or Taxol/FU-chemotherapy were applied. A radical transthoracic subtotal esophageal and proximal gastric resection through a right thoracoabdominal laparotomy with intrathoracic anastomosis was performed 6-8 weeks following RCT. This was combined with a two-field lymphadenectomy of mediastinal and abdominal lymph nodes. Standard histopathological evaluation included the application of regression grading according to Werner and Hoefler. Toxicity was recorded on the basis of CTC criteria; survival curves were calculated according to Kaplan-Meier. V10, V15, and V20 data were correlated with pulmonary toxicity. Results: Overall survival for all 23 patients was 61% at 3 years. Of the original 23 patients, 18 (78%) patients proceeded to radical surgery. Reasons for no surgery included advanced age of 79, 82, and 86 years (n = 3), severe comorbidity (n = 1), and progression during radiochemotherapy (n = 1). Surgical morbidity (grade 3-4) and mortality rates were 35% and 6%, respectively. Resurgery was necessary in 3 cases (18%). Clear resection margins were achieved in 17 of 18 patients (94%). Twelve of 18 (67%) patients initially diagnosed with T3 tumors and 3 of 3 patients with T4 tumors experienced downstaging. The ypN0 rate was 12 of 18 patients (67%). Out of a total of 18 patients, regression grading revealed < 10% viable cells in 8 (44%) including 3 cases (17%) with complete regression, 10-50% viable

Development and validation of a chronic copper biotic ligand model for Ceriodaphnia dubia

International Nuclear Information System (INIS)

Schwartz, Melissa L.; Vigneault, Bernard

2007-01-01

A biotic ligand model (BLM) to predict chronic Cu toxicity to Ceriodaphnia dubia was developed and tested. The effect of cationic competition, pH and natural organic matter complexation of Cu was examined to develop the model. There was no effect of cationic competition using increasing Ca and Na concentrations in our exposures. However, we did see a significant regression of decreasing toxicity (measured as the IC25; concentration at which there was a 25% inhibition of reproduction) as Mg concentration increased. However, taking into account the actual variability of the IC25 and since the relative increase in IC25 due to additional Mg was small (1.5-fold) Mg competition was not included in the model. Changes in pH had a significant effect on Cu IC25, which is consistent with proton competition as often suggested for acute BLMs. Finally, natural organic matter (NOM) was added to exposures resulting in significant decreases in toxicity. Therefore, our predictive model for chronic Cu toxicity to C. dubia includes the effect of pH and NOM complexation. The model was validated with Cu IC25 data generated in six natural surface waters collected from across Canada. Using WHAM VI, we calculated Cu speciation in each natural water and using our model, we generated 'predicted' IC25 data. We successfully predicted all Cu IC25 within a factor of 3 for the six waters used for validation

Do oil dispersants make spilled oil more toxic to fish?

International Nuclear Information System (INIS)

Hodson, P.

2010-01-01

The Deepwater Horizon blowout in the Gulf of Mexico was the world's largest oil spill in terms of duration and volume spilled. Clean-up operations, which involved the continuous and wide-spread use of oil dispersant at the surface and at the seabed discharge point at 1500 metres depth, gave rise to public concern about dispersant toxicity. Reports from the United States Environmental Protection Agency (EPA) claimed little difference in acute toxicity to marine fish and invertebrate species among commonly available dispersants and between dispersed and non-dispersed Louisiana Sweet Crude. Technically, the toxicity of waterborne hydrocarbons does not vary with chemical dispersion. However, the EPA omitted any consideration of loading, and misled the public about the risks of dispersant use in oil clean-up. This study examined the chronic toxicity of dispersed oil to fish embryos. The study revealed that toxicity expressed as oil loading increases by a factor of 10 to 1000 times with dispersion, largely because 10 to 1000 times more oil enters the water column. Since the action of dispersant is on the exposure component of the risk equation, not on the potency of the toxic components of oil, then the risk of oil toxicity to fish increases an equivalent amount.

Facts and Fallacies in the Debate on Glyphosate Toxicity

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Robin Mesnage

2017-11-01

Full Text Available The safety profile of the herbicide glyphosate and its commercial formulations is controversial. Reviews have been published by individuals who are consultants and employees of companies commercializing glyphosate-based herbicides in support of glyphosate’s reapproval by regulatory agencies. These authors conclude that glyphosate is safe at levels below regulatory permissible limits. In contrast, reviews conducted by academic scientists independent of industry report toxic effects below regulatory limits, as well as shortcomings of the current regulatory evaluation of risks associated with glyphosate exposures. Two authors in particular (Samsel and Seneff have published a series of commentaries proposing that long-term exposure to glyphosate is responsible for many chronic diseases (including cancers, diabetes, neuropathies, obesity, asthma, infections, osteoporosis, infertility, and birth defects. The aim of this review is to examine the evidential basis for these claimed negative health effects and the mechanisms that are alleged to be at their basis. We found that these authors inappropriately employ a deductive reasoning approach based on syllogism. We found that their conclusions are not supported by the available scientific evidence. Thus, the mechanisms and vast range of conditions proposed to result from glyphosate toxicity presented by Samsel and Seneff in their commentaries are at best unsubstantiated theories, speculations, or simply incorrect. This misrepresentation of glyphosate’s toxicity misleads the public, the scientific community, and regulators. Although evidence exists that glyphosate-based herbicides are toxic below regulatory set safety limits, the arguments of Samsel and Seneff largely serve to distract rather than to give a rational direction to much needed future research investigating the toxicity of these pesticides, especially at levels of ingestion that are typical for human populations.

Facts and Fallacies in the Debate on Glyphosate Toxicity

Science.gov (United States)

Mesnage, Robin; Antoniou, Michael N.

2017-01-01

The safety profile of the herbicide glyphosate and its commercial formulations is controversial. Reviews have been published by individuals who are consultants and employees of companies commercializing glyphosate-based herbicides in support of glyphosate’s reapproval by regulatory agencies. These authors conclude that glyphosate is safe at levels below regulatory permissible limits. In contrast, reviews conducted by academic scientists independent of industry report toxic effects below regulatory limits, as well as shortcomings of the current regulatory evaluation of risks associated with glyphosate exposures. Two authors in particular (Samsel and Seneff) have published a series of commentaries proposing that long-term exposure to glyphosate is responsible for many chronic diseases (including cancers, diabetes, neuropathies, obesity, asthma, infections, osteoporosis, infertility, and birth defects). The aim of this review is to examine the evidential basis for these claimed negative health effects and the mechanisms that are alleged to be at their basis. We found that these authors inappropriately employ a deductive reasoning approach based on syllogism. We found that their conclusions are not supported by the available scientific evidence. Thus, the mechanisms and vast range of conditions proposed to result from glyphosate toxicity presented by Samsel and Seneff in their commentaries are at best unsubstantiated theories, speculations, or simply incorrect. This misrepresentation of glyphosate’s toxicity misleads the public, the scientific community, and regulators. Although evidence exists that glyphosate-based herbicides are toxic below regulatory set safety limits, the arguments of Samsel and Seneff largely serve to distract rather than to give a rational direction to much needed future research investigating the toxicity of these pesticides, especially at levels of ingestion that are typical for human populations. PMID:29226121

Retrospective results of radiation therapy of the Eustachian tube in chronic otitis media

International Nuclear Information System (INIS)

Schultze, J.; Reinke, C.; Kimmig, B.; Frese, K.A.

2003-01-01

Background: The treatment results of symptomatic radiation therapy of the Eustachian tube in chronic otitis media had to be evaluated retrospectively. Patients and Methods: Between 1980 and 1997, 66 patients were referred for therapy. The median age was 58 years. In the clinical presentation, all the patients had a hearing impairment, 35 patients complained of pain, 21 had otorrhea. In their history, 20 patients indicated chronic recurrent infections. The complaints lasted for 4.7 years in the median, primary conservative (adstringentia, antibiotics) and surgical treatment (paracentesis, tympanic tubule, tympanoplastic) did not lead to lasting cure. In 40 of 66 patients, finally radiation therapy was done of both Eustachian tubes. With opposed fields and cobalt-60 photons a total dose of 6 Gy at single doses of 1 Gy, three times a week, was applied. Under the causes for exclusion of radiation therapy were non-acceptance of the patients (nine), prior radiation therapies (six) or spontaneous improvement after initial presentation in our department. The treatment results were evaluated by interviews of the patients and regular otorhinolaryngological examinations. Results: There were no side effects noticed. 28 of 40 (70%) patients reported a significant improvement that could be verified by objective otorhinolaryngological examinations. In the group of 26 nonirradiated patients, 22 could be interviewed indicating in 16 cases (72%) that the complaints were unchanged and chronic otitis media was lasting. In a subgroup analysis concerning the duration of otitis media radiation therapy proved more effective in an acute and subacute stadium of disease of up to 5 years duration, while the patients resistant to radiation therapy were entirely in a chronic stage of disease exceeding 5 years duration. (orig.) [de

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Science.gov (United States)

Gewandter, Jennifer S; Dworkin, Robert H; Turk, Dennis C; Farrar, John T; Fillingim, Roger B; Gilron, Ian; Markman, John D; Oaklander, Anne Louise; Polydefkis, Michael J; Raja, Srinivasa N; Robinson, James P; Woolf, Clifford J; Ziegler, Dan; Ashburn, Michael A; Burke, Laurie B; Cowan, Penney; George, Steven Z; Goli, Veeraindar; Graff, Ole X; Iyengar, Smriti; Jay, Gary W; Katz, Joel; Kehlet, Henrik; Kitt, Rachel A; Kopecky, Ernest A; Malamut, Richard; McDermott, Michael P; Palmer, Pamela; Rappaport, Bob A; Rauschkolb, Christine; Steigerwald, Ilona; Tobias, Jeffrey; Walco, Gary A

2015-07-01

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Quantitative analysis of potentially toxic metals in alginates for dental use

Directory of Open Access Journals (Sweden)

A. S. BRAGA

2009-01-01

Full Text Available

Alginate is one the materials most employed in practice to make dental impressions. Substances like zinc, cadmium and lead silicate, which are included in several alginate brands with the aim of improving their physical, chemical and mechanical properties, are a source of serious concern as regards their toxicity. The most serious chronic effect of oral exposure to cadmium is renal toxicity. Assimilation of lead has deleterious effects on the gastrointestinal tract, hematopoietic system, cardiovascular system, central and peripheral nervous systems, kidneys, immune system, and reproductive system. Chronic oral exposures to zinc have resulted in hypochromic and microcyte anemia in some individuals. The aim of the present study was to measure the cadmium, lead and zinc contents of seven brands of alginate for dental use on sale in Brazil. The samples were weighed and placed in the Teflon cups of a closedsystem microwave oven. Aqua regia (4mL concentrated HCl:HNO₃, 3:1 v/v and hydrofluoric acid (2mL concentrated HF were added to the samples, which were then subjected to heating. The samples were then cooled to room temperature and diluted to 25 mL in deionized water in a volumetric glass flask. The samples were diluted in duplicate and analyzed against a reagent blank. The analyses were performed in an atomic absorption flame spectrophotometer. Neither lead nor cadmium was detected. Zinc contents ranged from 0.001% to 1.36% by weight. The alginates exhibited low contents of the metals under study and gave no cause for concern regarding toxicity; even so, it is advisable to monitor potentially toxic materials continually and to analyze their plasmatic levels in the professionals working with them. Keywords: Cadmium, lead, zinc, alginates, intoxication, irreversible hydrocolloid.

Selective Thinning of the Perifoveal Inner Retina as an Early Sign of Hydroxychloroquine Retinal Toxicity

Science.gov (United States)

Pasadhika, Sirichai; Fishman, Gerald A; Choi, Dongseok; Shahidi, Mahnaz

2013-01-01

Purpose To evaluate macular thickness profiles using spectral-domain optical coherence tomography (SDOCT) and image segmentation in patients with chronic exposure to hydroxychloroquine. Methods This study included 8 patients with chronic exposure to hydroxychloroquine (Group 1) and 8 controls (Group 2). Group 1 patients had no clinically-evident retinal toxicity. All subjects underwent SDOCT imaging of the macula. An image segmentation technique was used to measure thickness of 6 retinal layers at 200 µm intervals. A mixed-effects model was used for multivariate analysis. Results By measuring total retinal thickness either at the central macular (2800 µm in diameter), the perifoveal region 1200-µm-width ring surrounding the central macula), or the overall macular area (5200 µm in diameter), there were no significant differences in the thickness between Groups 1 and 2. On an image segmentation analysis, selective thinning of the inner plexiform + ganglion cell layers (p=0.021) was observed only in the perifoveal area of the patients in Group 1 compared to that of Group 2 by using the mixed-effects model analysis. Conclusions Our results suggest that chronic exposure to hydroxychloroquine is associated with thinning of the perifoveal inner retinal layers, especially in the ganglion cell and inner plexiform layers, even in the absence of functional or structural clinical changes involving the photoreceptor or retinal pigment epithelial cell layers. This may be a contributing factor as the reason most patients who have early detectable signs of drug toxicity present with paracentral or pericentral scotomas. PMID:20395978

Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

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Richard Sauerheber

2013-01-01

Full Text Available The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

Physiologic conditions affect toxicity of ingested industrial fluoride.

Science.gov (United States)

Sauerheber, Richard

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

Antimony Toxicity

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Shyam Sundar

2010-12-01

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

Toxicity of lead (Pb) to freshwater green algae: Development and validation of a bioavailability model and inter-species sensitivity comparison

Energy Technology Data Exchange (ETDEWEB)

De Schamphelaere, K.A.C., E-mail: karel.deschamphelaere@ugent.be; Nys, C., E-mail: chnys.nys@ugent.be; Janssen, C.R., E-mail: colin.janssen@ugent.be

2014-10-15

Highlights: • Chronic toxicity of Pb varied 4-fold among three algae species. • The use of an organic P avoided Pb precipitation in the experiments. • pH and Dissolved Organic Carbon strongly affect Pb toxicity, Ca and Mg do not. • A bioavailability model was developed that accurately predicts toxicity. • Algae may become the most sensitive species to Pb above pH 7.4. - Abstract: Scientifically sound risk assessment and derivation of environmental quality standards for lead (Pb) in the freshwater environment are hampered by insufficient data on chronic toxicity and bioavailability to unicellular green algae. Here, we first performed comparative chronic (72-h) toxicity tests with three algal species in medium at pH 6, containing 4 mg fulvic acid (FA)/L and containing organic phosphorous (P), i.e. glycerol-2-phosphate, instead of PO{sub 4}{sup 3−} to prevent lead-phosphate mineral precipitation. Pseudokirchneriella subcapitata was 4-fold more sensitive to Pb than Chlorella kesslerii, with Chlamydomonas reinhardtii in the middle. The influence of medium physico-chemistry was therefore investigated in detail with P. subcapitata. In synthetic test media, higher concentrations of fulvic acid or lower pH protected against toxicity of (filtered) Pb to P. subcapitata, while effects of increased Ca or Mg on Pb toxicity were less clear. When toxicity was expressed on a free Pb{sup 2+} ion activity basis, a log-linear, 260-fold increase of toxicity was observed between pH 6.0 and 7.6. Effects of fulvic acid were calculated to be much more limited (1.9-fold) and were probably even non-existent (depending on the affinity constant for Pb binding to fulvic acid that was used for calculating speciation). A relatively simple bioavailability model, consisting of a log-linear pH effect on Pb{sup 2+} ion toxicity linked to the geochemical speciation model Visual Minteq (with the default NICA-Donnan description of metal and proton binding to fulvic acid), provided relatively

Toxicity of lead (Pb) to freshwater green algae: Development and validation of a bioavailability model and inter-species sensitivity comparison

International Nuclear Information System (INIS)

De Schamphelaere, K.A.C.; Nys, C.; Janssen, C.R.

2014-01-01

Highlights: • Chronic toxicity of Pb varied 4-fold among three algae species. • The use of an organic P avoided Pb precipitation in the experiments. • pH and Dissolved Organic Carbon strongly affect Pb toxicity, Ca and Mg do not. • A bioavailability model was developed that accurately predicts toxicity. • Algae may become the most sensitive species to Pb above pH 7.4. - Abstract: Scientifically sound risk assessment and derivation of environmental quality standards for lead (Pb) in the freshwater environment are hampered by insufficient data on chronic toxicity and bioavailability to unicellular green algae. Here, we first performed comparative chronic (72-h) toxicity tests with three algal species in medium at pH 6, containing 4 mg fulvic acid (FA)/L and containing organic phosphorous (P), i.e. glycerol-2-phosphate, instead of PO 4 3− to prevent lead-phosphate mineral precipitation. Pseudokirchneriella subcapitata was 4-fold more sensitive to Pb than Chlorella kesslerii, with Chlamydomonas reinhardtii in the middle. The influence of medium physico-chemistry was therefore investigated in detail with P. subcapitata. In synthetic test media, higher concentrations of fulvic acid or lower pH protected against toxicity of (filtered) Pb to P. subcapitata, while effects of increased Ca or Mg on Pb toxicity were less clear. When toxicity was expressed on a free Pb 2+ ion activity basis, a log-linear, 260-fold increase of toxicity was observed between pH 6.0 and 7.6. Effects of fulvic acid were calculated to be much more limited (1.9-fold) and were probably even non-existent (depending on the affinity constant for Pb binding to fulvic acid that was used for calculating speciation). A relatively simple bioavailability model, consisting of a log-linear pH effect on Pb 2+ ion toxicity linked to the geochemical speciation model Visual Minteq (with the default NICA-Donnan description of metal and proton binding to fulvic acid), provided relatively accurate toxicity

Acute and subacute toxicity of 18F-FDG

International Nuclear Information System (INIS)

Dantas, Danielle Maia

2013-01-01

Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the 18 F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical 18 F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of 18 F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

Lung inflammation caused by inhaled toxicants: a review

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Wong J

2016-06-01

Full Text Available John Wong, Bruce E Magun, Lisa J Wood School of Nursing, MGH Institute of Health Professions, Boston, MA, USA Abstract: Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials and those of heavy metals (from paint are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7 may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections. Keywords: cigarette, mycotoxin, trichothecene, ricin, inflammasome, macrophage, inhibitors

Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey

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Arora, Paul; Vasa, Priya; Brenner, Darren; Iglar, Karl; McFarlane, Phil; Morrison, Howard; Badawi, Alaa

2013-01-01

Background: Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults. Methods: We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status. Results: The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m2 or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%). Interpretation: The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease. PMID:23649413

A 27-years-old Man with Abdominal Pain; Lead Toxicity

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Maryam Kia

2017-12-01

Full Text Available Case presentation: A 27-year-old man came to our emergency department with chief complaints of abdominal pain, nausea and vomiting, colicky pain in all area of abdomen without any radiation and generalized myalgia. In his background, he had no previous medical problem. In his social history he had worked in an automobile battery-reclaiming factory for 5 years. During his physical examination, his appearance was pale with perioral priority, ill and agitated but not toxic with a blood pressure of 127/85 mmHg and a pulse of 80 beats/min, respiratory rate of 14 breaths/min and oral temperature of 37.3 °C, mild generalized abdominal tenderness without rebound. No obvious signs of sensory and motor neuropathy were found. In the head and neck examination, we found lead-lined teeth. Learning points: The most common cause of chronic metal poisoning is lead. Exposure occurs through inhalation or ingestion. Both inorganic and organic forms of lead that exist naturally produce clinical toxicity. Gastrointestinal manifestations occur more frequently with acute rather than with chronic poisoning, and concurrent hemolysis may cause the colicky abdominal pains. Patients may have complained of a metallic taste and, with long-term exposure, have bluish-gray gingival lead lines. In addition, constitutional symptoms, including arthralgia, generalized weakness, and weight loss raises the possibility of lead toxicity.

Herbicide toxicity on river biofilms assessed by pulse amplitude modulated (PAM) fluorometry

International Nuclear Information System (INIS)

Kim Tiam, Sandra; Laviale, Martin; Feurtet-Mazel, Agnès; Jan, Gwilherm; Gonzalez, Patrice; Mazzella, Nicolas; Morin, Soizic

2015-01-01

Highlights: • Rapid Light Curves were shown to be early markers of toxicant exposure. • Diuron and norflurazon effects were significant at environmentally realistic concentrations. • Toxic effects in intact biofilms seem to be delayed compared to disrupted biofilms. - Abstract: The use of Rapid light curves (RLCs) as a toxicity endpoint for river biofilms was examined in this study and compared to “classical fluorescence parameters” i.e. minimal fluorescence (F 0 ), optimal and effective quantum yields of photosystem II (F v /F m and Φ PSII ). Measurements were performed after exposure to five concentrations of diuron (from 0.3 to 33.4 μg L −1 ), its main degradation product (DCPMU) (from 1.0 to 1014 μg L −1 ) and norflurazon (from 0.6 to 585 μg L −1 ) with the lowest exposure concentrations corresponding to levels regularly encountered in chronically contaminated sites. Biofilm responses were evaluated after 1, 5, 7 and 14 days of exposure to the different toxicants. Overall, the responses of both “classical fluorescence parameters” and RLC endpoints were highly time dependent and related to the mode of action of the different compounds. Interestingly, parameters calculated from RLCs (α, ETR max and I k ) were useful early markers of pesticide exposure since they revealed significant effects of all the tested toxicants from the first day of exposure. In comparison, classical fluorescence endpoints (F 0 and F v /F m ) measured at day 1 were only affected in the DCPMU treatment. Our results demonstrated the interest of RLCs as early markers of toxicant exposure particularly when working with toxicants with less specific mode of action than PSII inhibitors

Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea

International Nuclear Information System (INIS)

Wagner, H. Jr.; McKeough, P.G.; Desforges, J.; Madoc-Jones, H.

1986-01-01

Seventeen patients with either chronic myelogenous leukemia (CML) or myelofibrosis with myeloid metaplasia (MMM) received 24 courses of splenic irradiation at this institution from 1973 to 1982. Eleven of the 17 patients had received prior chemotherapy. Patients were treated with 60 Co gamma rays or 6 MV photons. The fraction size ranged from 15 to 100 rad and the total dose per treatment course from 15 to 650 rad, with the exception of one patient who received 1650 rad. Fourteen of 19 courses (71%) given for splenic pain yielded significant subjective relief while 17 of 26 courses given for splenomegaly obtained at least 50% regression of splenic size. Blood counts were carefully monitored before each treatment to limit hematologic toxicity. From this experience, the authors conclude that splenic irradiation effectively palliates splenic pain and reverses splenomegaly in the majority of patients with CML and MMM. Intermittent fractionation (twice or thrice weekly) is more convenient for the patient, appears to be as effective as daily treatment, and may be associated with less hematologic toxicity. Preliminary results of concurrent treatment with splenic irradiation and oral hydroxyurea show promise and warrant further study

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

Science.gov (United States)

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...

The chronic pain in back and new methods of treatment

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Irina Dolgova

2015-02-01

Full Text Available  Aim The study of the prevalence causes the formation of chronic vertebrogenic pain syndromes (СVPS, their clinical course, determining the optimal methods of treatment. Methods The observation of the 31 patients with chronic vertebrogenic pain syndrome was led. It is identified neuroimaging changes and leading clinical and neurological syndromes. An objective assessment of the presence of pain confirmed using a visual analog scale and the test for the assessment of pain and functional economic status in chronic backpain. All patients were devided into 2 groups.Results The duration of chronic vertebrogenic pain patients studied were: from 3 to 5 years in 11 (35 %, more than 10 years in 13 (42 %, more than 15 years – in 7 (23% patients. A significant duration of the pain syndrome was the reason for seeking care. Comparing the results of treatment in the two groups showed a significant benefit in the primary group, in which after 10 days the patients did not report pain and returned to work. In the control group revealed a statistically significant reduction of pain syndrome, the condition of patients required further rehabilitation.Conclusions It is identified the best effect with the use of modern methods of treatment of reflex muscle-toxic with Xeomin in comparison with traditional methods

Evaluation of surficial sediment toxicity and sediment physico-chemical characteristics of representative sites in the Lagoon of Venice (Italy)

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Losso, C.; Arizzi Novelli, A.; Picone, M.; Marchetto, D.; Pessa, G.; Molinaroli, E.; Ghetti, P. F.; Volpi Ghirardini, A.

2004-11-01

Toxic hazard in sites with varying types and levels of contamination in the Lagoon of Venice was estimated by means of toxicity bioassays based on the early life-stages of the autochthonous sea urchin Paracentrotus lividus. Elutriate was chosen as the test matrix, due to its ability to highlight potential toxic effects towards sensitive biological components of the water column caused by sediment resuspension phenomena affecting the Lagoon. Surficial sediments (core-top 5 cm deep), directly influenced by resuspension/redeposition processes, and core sediments (core 20 cm deep), recording time-mediated contamination, were sampled in some sites located in the lagoonal area most greatly influenced by anthropogenic activities. Particle size, organic matter and water content were also analysed. In two sites, the results of physical parameters showed that the core-top sediments were coarser than the 20-cm core sediments. Sperm cell toxicity test results showed the negligible acute toxicity of elutriates from all investigated sites. The embryo toxicity test demonstrated a short-term chronic toxicity gradient for elutriates from the 20-cm core sediments, in general agreement both with the expected contamination gradient and with results of the Microtox® solid-phase test. Elutriates of the core-top 5-cm sediments revealed a totally inverted gradient, in comparison with that for the 20-cm core sediments, and the presence of a "hot spot" of contamination in the site chosen as a possible reference. Investigations on ammonia and sulphides as possible confounding factors excluded their contribution to this "hot spot". Integrated physico-chemical and toxicity results on sediments at various depths demonstrated the presence of disturbed sediments in the central basin of the Lagoon of Venice.

Interaction of paracetamol in chronic alcoholic patients. Importance for odontologists.

Science.gov (United States)

Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio

2008-04-01

For social, cultural and historical motives alcohol (ethanol or isopenthanol) is considered to be just a beverage rather than a liquor. However, from a pharmatherapeutic point of view alcohol is a depressor of the central nervous system. The effects of alcohol consumption can range from raised loquacity to drunkenness, loss of consciousness and death as a result of insufficient respiration. Probably the most frequent pharmacological interaction is the combination of alcohol with other depressors of the central nervous system which increases the depression even further. Some medicaments which more frequently produce an interaction are antihistamines, analgesics, antidepressants and medicaments for coughs, common cold and influenza. Paracetamol or acetaminophen is an analgesic medicament similar to acetylsalicylic acid lacking anticoagulatory properties and gastric irritation. However, its major drawback is hepatic toxicity as a result of a toxic metabolite produced in the liver by cytochrome P-450, principally cytochrome CYP2E1, which is detoxified under normal conditions by hepatic glutathione. Ethanol is also detoxified by CYP2E1, which is an inducer of ethanol such that chronic ingestion increases the level of this enzyme. When the ingestion of alcohol is stopped, CYP2E1 is greatly increased and only metabolises the paracetamol giving rise to high quantities of hepatotoxic metabolites so that the hepatic glutathione is unable to detoxify resulting in irreversible hepatic damage. Therefore for odontologists it is important that in chronic alcoholic patients the consumption of alcohol should not be suspended on prescribing paracetamol.

Pattern analysis of patients with temporomandibular disorders resulting from unilateral mastication due to chronic periodontitis

Science.gov (United States)

2017-01-01

Purpose The purpose of the present study was to perform a pattern analysis in patients with temporomandibular disorder (TMD) resulting from unilateral mastication due to chronic periodontitis. Methods Thirty participants with signs or symptoms of TMD who engaged in unilateral mastication due to periodontitis-related discomfort (test group) were selected. Another 30 subjects exhibiting signs or symptoms of TMD resulting from unilateral mastication not due to chronic periodontitis (control group) were also recruited. An interview-based questionnaire was administered, and an examination of the temporomandibular joint (TMJ) with determination of periodontal status was performed. Results The duration of unilateral mastication was significantly longer in the control group than in the test group. There was a significant negative correlation between the duration of unilateral mastication and the Community Periodontal Index score. Using the Research Diagnostic Criteria for TMD (RDC/TMD) axis I algorithms, all the subjects were assigned to 3 main groups. The test group exhibited significantly a higher diagnostic distribution of group III (arthralgia, osteoarthritis, or osteoarthrosis), and in both the test and control groups, the number of diagnoses was larger for the non-chewing side. The control group showed a significantly higher diagnostic distribution of group I (myofacial pain), and in both the test and control groups, the number of diagnoses was larger for the chewing side. Conclusions The results of the present study indicate that unilateral mastication due to chronic periodontitis could induce not only pain but also structural TMJ changes if adequate treatment is not administered and supported within a short time from the onset of the condition. Therefore, immediate treatment of chronic periodontitis is recommended to prevent not only the primary progress of periodontal disease, but also secondary TMJ-related problems. Furthermore, subjects who have suffered chronic

Application of toxicity testing in the evaluation of reclamation options for oil sands fine tails

International Nuclear Information System (INIS)

Nelson, L.R.; MacKinnon, M.; Gulley, J.R.

1993-01-01

The hot water process for the extraction of bitumen from oil sands leads to the production of large volumes of wastewater and the formation of a large inventory of fine clay tailings. This fine tailings material and its associated water are acutely toxic to various aquatic test organisms during bioassays. An overview is presented of toxicity testing at Syncrude and Suncor, the application of toxicity testing to fine tailings management, and the role in reclamation planning. The main acutely toxic component of the tailings is the polar organic acid fraction, specifically naphthanates. These naphthanates are readily degraded biologically by indigenous microbial populations. Toxicity testing is aimed at assessing the degree of both acute and chronic toxicity and the long term potential for the input of toxins into the environment from various proposed reclamation measures. 28 refs., 6 figs., 2 tabs

Provider confidence in opioid prescribing and chronic pain management: results of the Opioid Therapy Provider Survey

Science.gov (United States)

Pearson, Amy CS; Moman, Rajat N; Moeschler, Susan M; Eldrige, Jason S; Hooten, W Michael

2017-01-01

Introduction Many providers report lack of confidence in managing patients with chronic pain. Thus, the primary aim of this study was to investigate the associations of provider confidence in managing chronic pain with their practice behaviors and demographics. Materials and methods The primary outcome measure was the results of the Opioid Therapy Provider Survey, which was administered to clinicians attending a pain-focused continuing medical education conference. Nonparametric correlations were assessed using Spearman’s rho. Results Of the respondents, 55.0% were women, 92.8% were white, and 56.5% were physicians. Primary care providers accounted for 56.5% of the total respondents. The majority of respondents (60.8%) did not feel confident managing patients with chronic pain. Provider confidence in managing chronic pain was positively correlated with 1) following an opioid therapy protocol (P=0.001), 2) the perceived ability to identify patients at risk for opioid misuse (P=0.006), and 3) using a consistent practice-based approach to improve their comfort level with prescribing opioids (Pcorrelated with the perception that treating pain patients was a “problem in my practice” (P=0.005). Conclusion In this study, the majority of providers did not feel confident managing chronic pain. However, provider confidence was associated with a protocolized and consistent practice-based approach toward managing opioids and the perceived ability to identify patients at risk for opioid misuse. Future studies should investigate whether provider confidence is associated with measurable competence in managing chronic pain and explore approaches to enhance appropriate levels of confidence in caring for patients with chronic pain. PMID:28652805

Chronic toxicity and hazard assessment of an inorganic mixture simulating irrigation drainwater to razorback sucker and bonytail

Science.gov (United States)

Hamilton, Steven J.; Buhl, Kevin J.; Bullard, Fern A.; Little, Edward E.

2000-01-01

We conducted two 90 day chronic toxicity studies with two endangered fish, razorback sucker and bonytail. Swim-up larvae were exposed in a reconstituted water simulating the middle Green River. The toxicant mixture simulated the environmental ratio and concentrations of inorganics reported in a Department of the Interior study for the mouth of Ashley Creek on the Green River, and was composed of nine elements. The mixture was tested at 1X, 2X, 4X, 8X, and 16X where X was the measured environmental concentration (2 μg/L arsenic, 630 μg/L boron, 10 μg/L copper, 5 μg/L molybdenum, 51 μg/L selenate, 8 μg/L selenite, 33 μg/L uranium, 2 μg/L vanadium, and 20 μg/L zinc). Razorback sucker had reduced survival after 60 days exposure to the inorganic mixture at 8X, whereas growth was reduced after 30 and 60 days at 2X and after 90 days at 4X. Bonytail had reduced survival after 30 days exposure at 16X, whereas growth was reduced after 30, 60, and 90 days at 8X. Swimming performance of razorback sucker and bonytail were reduced after 60 and 90 days of exposure at 8X. Whole-body residues of copper, selenium, and zinc increased in a concentration-response manner and seemed to be regulated at 90 days of exposure at 4X and lower treatments for razorback sucker, and at 8X and lower for bonytail. Adverse effects occurred in fish with whole-body residues of copper, selenium, and zinc similar to those causing similar effects in other fish species. Comparison of adverse effect concentrations with measured environmental concentrations showed a high hazard to the two endangered fish. Irrigation activities may be a contributing factor to the decline of these endangered fishes in the middle Green River. 

Toxic effects of NH4+-N on embryonic development of Bufo gargarizans and Rana chensinensis.

Science.gov (United States)

Deng, Hongzhang; Chai, Lihong; Luo, Pingping; Zhou, Meimei; Nover, Daniel; Zhao, Xiaohong

2017-09-01

Although nitrogen fertilizer is commonly used worldwide, little information is currently available about NH 4 + -N toxicity on amphibians. This study determined the acute and chronic toxic effects of NH 4 + -N on two native Chinese amphibian species (Bufo gargarizans and Rana chensinensis), and compared the negative sensitivity of different embryos to NH 4 + -N. Static renewal aqueous exposures were performed using B. gargarizans and R. chensinensis embryos at Gosner stage 2 over 96 h. In terms of 96 h-LC 50 , B. gargarizans and R. chensinensis embryos had significantly different responses to NH 4 + -N, and the latter was more sensitive to NH 4 + -N than the former. In the chronic toxicity test, exposure to 10 mg L -1 NH 4 + -N or higher significantly decreased the hatching rate of embryos in both species. Significant increases in the abnormality rate of embryos at 50 mg L -1 NH 4 + -N or higher were observed and morphological abnormalities were characterized by axial flexures, yolk sac edema, and hyperplasia in both species. Additionally, the total length of embryos decreased in a dose-dependent manner after exposure to NH 4 + -N. The results indicate that NH 4 + -N exposure can increase abnormality and inhibit the hatching and development of embryos in B. gargarizans and R. chensinensis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative In Vitro Biological Toxicity of Four Kinds of Air Pollution Particles.

Science.gov (United States)

Shin, Han-Jae; Cho, Hyun Gi; Park, Chang Kyun; Park, Ki Hong; Lim, Heung Bin

2017-10-01

Accumulating epidemiological evidence indicates that exposure to fine air pollution particles (APPs) is associated with a variety of adverse health effects. However, the exact physiochemical properties and biological toxicities of fine APPs are still not well characterized. We collected four types of fine particle (FP) (diesel exhaust particles [DEPs], natural organic combustion [NOC] ash, synthetic organic combustion [SOC] ash, and yellow sand dust [YSD]) and investigated their physicochemical properties and in vitro biological toxicity. DEPs were almost entirely composed of ultrafine particles (UFPs), while the NOC, SOC, and YSD particles were a mixture of UFPs and FPs. The main elements in the DEPs, NOC ash, SOC ash, and YSD were black carbon, silicon, black carbon, and silicon, respectively. DEPs exhibited dose-dependent mutagenicity even at a low dose in Salmonella typhimurium TA 98 and 100 strains in an Ames test for genotoxicity. However, NOC, SOC, and YSD particles did not show any mutagenicity at high doses. The neutral red uptake assay to test cell viability revealed that DEPs showed dose-dependent potent cytotoxicity even at a low concentration. The toxicity of DEPs was relatively higher than that of NOC, SOC, and YSD particles. Therefore, these results indicate that among the four FPs, DEPs showed the highest in vitro biological toxicity. Additional comprehensive research studies such as chemical analysis and in vivo acute and chronic inhalation toxicity tests are necessary to determine and clarify the effects of this air contaminant on human health.

Reproductive impairment in the zebrafish, Danio rerio, upon chronic exposure to 1,2,3-trichlorobenzene.

NARCIS (Netherlands)

Roex, E.W.M.; Giovannangelo, M.E.C.A.; van Gestel, C.A.M.

2001-01-01

Most organic pollutants are supposed to act via the mechanism of nonpolar narcosis upon acute exposure. Because the chronic effects of these compounds are still relatively unknown, in this study a chronic toxicity experiment was performed with zebrafish, Danio rerio, exposed to 1, 2,

Chronic exposure of zinc oxide nanoparticles causes deviant phenotype in Drosophila melanogaster

Energy Technology Data Exchange (ETDEWEB)

Anand, Avnika Singh; Prasad, Dipti N.; Singh, Shashi Bala; Kohli, Ekta, E-mail: ektakohli@hotmail.com

2017-04-05

Zinc oxide nanoparticles (ZnO NPs) are commonly used nanomaterials (NMs) with versatile applications from high-end technologies to household products. This pervasive utilisation has brought human in the close interface with nanoparticles (NPs), hence questioning their safety prior to usage is a must. In this study, we have assessed the effects of chronic exposure to ZnO NPs (<50 nm) on the model organism Drosophila melanogaster. Potential toxic effects were studied by evaluating longevity, climbing ability, oxidative stress and DNA fragmentation. Ensuing exposure, the F0 (parent), F1, F2, F3 and F4 generation flies were screened for the aberrant phenotype. Flies exposed to ZnO NPs showed distinctive phenotypic changes, like deformed segmented thorax and single or deformed wing, which were transmitted to the offspring’s in subsequent generations. The unique abnormal phenotype is evident of chronic toxicity induced by ZnO NPs, although appalling, it strongly emphasize the importance to understand NPs toxicity for safer use.

Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

International Nuclear Information System (INIS)

Lim, Tee S.; Cheung, Patrick; Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

2008-01-01

Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity

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

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Li Li

2016-01-01

Full Text Available 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 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.

Uranium: biokinetics and toxicity; Biocinetique et toxicite de l'uranium

Energy Technology Data Exchange (ETDEWEB)

Menetrier, F.; Renaud-Salis, V.; Flury-Herard, A

2000-07-01

This report was achieved as a part of a collaboration with the Fuel Cycle Direction. Its aim was to give the state of the art about: the behaviour of uranium in the human organism (biokinetics) after ingestion, its toxicity (mainly renal) and the current regulation about its incorporation. Both in the upstream and in the downstream of the fuel cycle, uranium remains, quantitatively, the first element in the cycle which is, at the present time, temporarily disposed or recycled. Such a considerable quantity of uranium sets the problem of its risk on the health. In the long term, the biosphere may be affected and consequently the public may ingest water or food contaminated with uranium. In this way, radiological and chemical toxicity risk may be activated. This report emphasizes: the necessity of confirming some experimental and epidemiological biokinetic data used or not in the ICRP models. Unsolved questions remain about the gastrointestinal absorption according to chemical form (valency state, mixtures...), mass and individual variations (age, disease) further a chronic ingestion of uranium. It is well established that uranium is mainly deposited in the skeleton and the kidney. But the skeleton kinetics following a chronic ingestion and especially in some diseases has to be more elucidated; the necessity of taking into account uranium at first as a chemical toxic, essentially in the kidney and determining the threshold of functional lesion. In this way, it is important to look for some specific markers; the problem of not considering chemical toxicity of uranium in the texts regulating its incorporation.

Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats

International Nuclear Information System (INIS)

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

2003-01-01

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

Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy

LENUS (Irish Health Repository)

Bratland, Ase

2011-04-08

Abstract Background In early-phase studies with targeted therapeutics and radiotherapy, it may be difficult to decide whether an adverse event should be considered a dose-limiting toxicity (DLT) of the investigational systemic agent, as acute normal tissue toxicity is frequently encountered with radiation alone. We have reanalyzed the toxicity data from a recently conducted phase 1 study on vorinostat, a histone deacetylase inhibitor, in combination with pelvic palliative radiotherapy, with emphasis on the dose distribution within the irradiated bowel volume to the development of DLT. Findings Of 14 eligible patients, three individuals experienced Common Terminology Criteria of Adverse Events grade 3 gastrointestinal and related toxicities, representing a toxicity profile vorinostat has in common with radiotherapy to pelvic target volumes. For each study patient, the relative volumes of small bowel receiving radiation doses between 6 Gy and 30 Gy at 6-Gy intervals (V6-V30) were determined from the treatment-planning computed tomography scans. The single patient that experienced a DLT at the second highest dose level of vorinostat, which was determined as the maximum-tolerated dose, had V6-V30 dose-volume estimates that were considerably higher than any other study patient. This patient may have experienced an adverse radiation dose-volume effect rather than a toxic effect of the investigational drug. Conclusions When reporting early-phase trial results on the tolerability of a systemic targeted therapeutic used as potential radiosensitizing agent, radiation dose-volume effects should be quantified to enable full interpretation of the study toxicity profile. Trial registration ClinicalTrials.gov: NCT00455351

Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy

International Nuclear Information System (INIS)

Bratland, Åse; Dueland, Svein; Hollywood, Donal; Flatmark, Kjersti; Ree, Anne H

2011-01-01

In early-phase studies with targeted therapeutics and radiotherapy, it may be difficult to decide whether an adverse event should be considered a dose-limiting toxicity (DLT) of the investigational systemic agent, as acute normal tissue toxicity is frequently encountered with radiation alone. We have reanalyzed the toxicity data from a recently conducted phase 1 study on vorinostat, a histone deacetylase inhibitor, in combination with pelvic palliative radiotherapy, with emphasis on the dose distribution within the irradiated bowel volume to the development of DLT. Of 14 eligible patients, three individuals experienced Common Terminology Criteria of Adverse Events grade 3 gastrointestinal and related toxicities, representing a toxicity profile vorinostat has in common with radiotherapy to pelvic target volumes. For each study patient, the relative volumes of small bowel receiving radiation doses between 6 Gy and 30 Gy at 6-Gy intervals (V6-V30) were determined from the treatment-planning computed tomography scans. The single patient that experienced a DLT at the second highest dose level of vorinostat, which was determined as the maximum-tolerated dose, had V6-V30 dose-volume estimates that were considerably higher than any other study patient. This patient may have experienced an adverse radiation dose-volume effect rather than a toxic effect of the investigational drug. When reporting early-phase trial results on the tolerability of a systemic targeted therapeutic used as potential radiosensitizing agent, radiation dose-volume effects should be quantified to enable full interpretation of the study toxicity profile.

Multiple inorganic toxic substances contaminating the groundwater of Myingyan Township, Myanmar: Arsenic, manganese, fluoride, iron, and uranium

Energy Technology Data Exchange (ETDEWEB)

Bacquart, Thomas [Better Life Laboratories, Calais, VT (United States); Frisbie, Seth [Better Life Laboratories, Calais, VT (United States); Department of Chemistry and Biochemistry, Norwich University, Northfield, VT (United States); Mitchell, Erika [Better Life Laboratories, Calais, VT (United States); Grigg, Laurie [Department of Earth and Environmental Science, Norwich University, Northfield, VT (United States); Cole, Christopher [Department of Chemistry and Biochemistry, Norwich University, Northfield, VT (United States); Small, Colleen [Vermont Department of Health Laboratory, Burlington, VT (United States); Sarkar, Bibudhendra, E-mail: bsarkar@sickkids.ca [Department of Molecular Structure and Function, The Research Institute of The Hospital for Sick Children, University of Toronto, Toronto, Ontario (Canada); Department of Biochemistry, University of Toronto, Toronto, Ontario (Canada)

2015-06-01

In South Asia, the technological and societal shift from drinking surface water to groundwater has resulted in a great reduction of acute diseases due to water borne pathogens. However, arsenic and other naturally occurring inorganic toxic substances present in groundwater in the region have been linked to a variety of chronic diseases, including cancers, heart disease, and neurological problems. Due to the highly specific symptoms of chronic arsenic poisoning, arsenic was the first inorganic toxic substance to be noticed at unsafe levels in the groundwater of West Bengal, India and Bangladesh. Subsequently, other inorganic toxic substances, including manganese, uranium, and fluoride have been found at unsafe levels in groundwater in South Asia. While numerous drinking water wells throughout Myanmar have been tested for arsenic, relatively little is known about the concentrations of other inorganic toxic substances in Myanmar groundwater. In this study, we analyzed samples from 18 drinking water wells (12 in Myingyan City and 6 in nearby Tha Pyay Thar Village) and 2 locations in the Ayeyarwaddy River for arsenic, boron, barium, beryllium, cadmium, cobalt, chromium, copper, fluoride, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, uranium, vanadium, and zinc. Concentrations of arsenic, manganese, fluoride, iron, or uranium exceeded health-based reference values in most wells. In addition, any given well usually contained more than one toxic substance at unsafe concentrations. While water testing and well sharing could reduce health risks, none of the wells sampled provide water that is entirely safe with respect to inorganic toxic substances. It is imperative that users of these wells, and users of other wells that have not been tested for multiple inorganic toxic substances throughout the region, be informed of the need for drinking water testing and the health consequences of drinking water contaminated with inorganic toxic

Multiple inorganic toxic substances contaminating the groundwater of Myingyan Township, Myanmar: Arsenic, manganese, fluoride, iron, and uranium

International Nuclear Information System (INIS)

Bacquart, Thomas; Frisbie, Seth; Mitchell, Erika; Grigg, Laurie; Cole, Christopher; Small, Colleen; Sarkar, Bibudhendra

2015-01-01

In South Asia, the technological and societal shift from drinking surface water to groundwater has resulted in a great reduction of acute diseases due to water borne pathogens. However, arsenic and other naturally occurring inorganic toxic substances present in groundwater in the region have been linked to a variety of chronic diseases, including cancers, heart disease, and neurological problems. Due to the highly specific symptoms of chronic arsenic poisoning, arsenic was the first inorganic toxic substance to be noticed at unsafe levels in the groundwater of West Bengal, India and Bangladesh. Subsequently, other inorganic toxic substances, including manganese, uranium, and fluoride have been found at unsafe levels in groundwater in South Asia. While numerous drinking water wells throughout Myanmar have been tested for arsenic, relatively little is known about the concentrations of other inorganic toxic substances in Myanmar groundwater. In this study, we analyzed samples from 18 drinking water wells (12 in Myingyan City and 6 in nearby Tha Pyay Thar Village) and 2 locations in the Ayeyarwaddy River for arsenic, boron, barium, beryllium, cadmium, cobalt, chromium, copper, fluoride, iron, mercury, manganese, molybdenum, nickel, lead, antimony, selenium, thallium, uranium, vanadium, and zinc. Concentrations of arsenic, manganese, fluoride, iron, or uranium exceeded health-based reference values in most wells. In addition, any given well usually contained more than one toxic substance at unsafe concentrations. While water testing and well sharing could reduce health risks, none of the wells sampled provide water that is entirely safe with respect to inorganic toxic substances. It is imperative that users of these wells, and users of other wells that have not been tested for multiple inorganic toxic substances throughout the region, be informed of the need for drinking water testing and the health consequences of drinking water contaminated with inorganic toxic

A fresh look at road salt: aquatic toxicity and water-quality impacts on local, regional, and national scales.

Science.gov (United States)

Corsi, Steven R; Graczyk, David J; Geis, Steven W; Booth, Nathaniel L; Richards, Kevin D

2010-10-01

A new perspective on the severity of aquatic toxicity impact of road salt was gained by a focused research effort directed at winter runoff periods. Dramatic impacts were observed on local, regional, and national scales. Locally, samples from 7 of 13 Milwaukee, Wisconsin area streams exhibited toxicity in Ceriodaphnia dubia and Pimephales promelas bioassays during road-salt runoff. Another Milwaukee stream was sampled from 1996 to 2008 with 72% of 37 samples exhibiting toxicity in chronic bioassays and 43% in acute bioassays. The maximum chloride concentration was 7730 mg/L. Regionally, in southeast Wisconsin, continuous specific conductance was monitored as a chloride surrogate in 11 watersheds with urban land use from 6.0 to 100%. Elevated specific conductance was observed between November and April at all sites, with continuing effects between May and October at sites with the highest specific conductance. Specific conductance was measured as high as 30,800 μS/cm (Cl = 11,200 mg/L). Chloride concentrations exceeded U.S. Environmental Protection Agency (USEPA) acute (860 mg/L) and chronic (230 mg/L) water-quality criteria at 55 and 100% of monitored sites, respectively. Nationally, U.S. Geological Survey historical data were examined for 13 northern and 4 southern metropolitan areas. Chloride concentrations exceeded USEPA water-quality criteria at 55% (chronic) and 25% (acute) of the 168 monitoring locations in northern metropolitan areas from November to April. Only 16% (chronic) and 1% (acute) of sites exceeded criteria from May to October. At southern sites, very few samples exceeded chronic water-quality criteria, and no samples exceeded acute criteria.

Chronic pesticide exposure and consequential keratectasia & corneal neovascularisation.

Science.gov (United States)

Sanyal, Shalini; Law, Atrayo; Law, Sujata

2017-11-01

Ocular toxicity as a consequence of chronic pesticide exposure is one of the health hazards caused due to extended exposure to pesticides. The cornea, due to its position as the outer ocular layer and its role in protecting the internal layers of the eye; is gravely affected by this xenobiotic insult to the eye, leading to ocular irritation and damage to normal vision. The deleterious effects of chronic pesticide exposure on the various corneal layers and the ocular risks involved therein, were explored by mimicking the on-field scenario. Cytological, histological and flowcytometric parameters were taken into consideration to determine the enhanced risk of corneal neovascularisation and keratectasia, specifically, keratoconus. Chronic exposure to pesticides leads to heightened ocular morbidity wherein there were visible pathophysiological changes to the ocular surface. The cornea was found to be adversely affected with visible protuberance in a cone-like shape, characteristic of keratoconus in a majority of the experimental animals. Further analyses revealed a detrimental impact on all the corneal layers and an amplified expression of inflammation markers such as TNF-α, VCAM-1 and ICAM-1. Additionally, it was found that post pesticide exposure, the corneal surface developed hypoxia, leading to a significant increase of angiogenesis promoting factors and consequential neovascularisation. Apart from ocular toxicity, chronic exposure to pesticides significantly increases the risks of keratectasia and corneal neovascularisation; disorders which lead to diminished vision and if untreated, blindness. Copyright © 2017 Elsevier Ltd. All rights reserved.

Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcome results with rapid arc

Directory of Open Access Journals (Sweden)

Fogliata Antonella

2010-10-01

Full Text Available Abstract Background To report acute toxicity, initial outcome results and planning therapeutic parameters in radiation treatment of advanced lung cancer (stage III with volumetric modulated arcs using RapidArc (RA. Methods Twenty-four consecutive patients were treated with RA. All showed locally advanced non-small cell lung cancer with stage IIIA-IIIB and with large volumes (GTV:299 ± 175 cm3, PTV:818 ± 206 cm3. Dose prescription was 66Gy in 33 fractions to mean PTV. Delivery was performed with two partial arcs with a 6 MV photon beam. Results From a dosimetric point of view, RA allowed us to respect most planning objectives on target volumes and organs at risk. In particular: for GTV D1% = 105.6 ± 1.7%, D99% = 96.7 ± 1.8%, D5%-D95% = 6.3 ± 1.4%; contra-lateral lung mean dose resulted in 13.7 ± 3.9Gy, for spinal cord D1% = 39.5 ± 4.0Gy, for heart V45Gy = 9.0 ± 7.0Gy, for esophagus D1% = 67.4 ± 2.2Gy. Delivery time was 133 ± 7s. At three months partial remission > 50% was observed in 56% of patients. Acute toxicities at 3 months showed 91% with grade 1 and 9% with grade 2 esophageal toxicity; 18% presented grade 1 and 9% with grade 2 pneumonia; no grade 3 acute toxicity was observed. The short follow-up does not allow assessment of local control and progression free survival. Conclusions RA proved to be a safe and advantageous treatment modality for NSCLC with large volumes. Long term observation of patients is needed to assess outcome and late toxicity.

Different modes of TiO2 uptake by Ceriodaphnia dubia: relevance to toxicity and bioaccumulation.

Science.gov (United States)

Dalai, Swayamprava; Iswarya, V; Bhuvaneshwari, M; Pakrashi, Sunandan; Chandrasekaran, N; Mukherjee, Amitava

2014-07-01

The extensive environmental exposure of engineered metal oxide nanoparticles (NPs) may result in their bioaccumulation in aquatic organisms leading to their biotransfer in a food chain through various routes in a freshwater ecosystem. The present study focuses on the possible modes of TiO2 NP trophic transfer to Ceriodaphnia dubia, in presence and/absence of its diet, Scenedesmus obliquus (primary producer). The acute exposure studies (48h) were designed to have daphnids exposed to (i) the free NPs, (ii) both the free and the algae-borne NPs; and (iii) only the algae-borne NPs in separate tests to understand the possible routes of NP transfer. The dietary uptake of TiO2 NPs (algae-borne) was found to be the primary route for NP biotransfer with ∼70% of total NP uptake. Interestingly, in a separate study it was noticed that the NPs coated with algal exudates were easily taken up by daphnids as compared to pristine NPs of same concentrations, leading to their higher bioaccumulation. A chronic toxicity study, where daphnids were exposed to both free and algae-borne NPs for 21 days was undertaken to comprehend the TiO2 NP effect on daphnia growth and reproduction upon chronic exposure and also the bioaccumulation potential. Both acute and chronic exposure studies suggested higher bioaccumulation of TiO2 in daphnids when the particles were less toxic to the diet (algae). Copyright © 2014 Elsevier B.V. All rights reserved.

Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests

International Nuclear Information System (INIS)

Arts, Gertie H.P.; Belgers, J. Dick M.; Hoekzema, Conny H.; Thissen, Jac T.N.M.

2008-01-01

The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root endpoints, reflecting root growth, were most sensitive in the toxicity tests, while endpoints relating to biomass, growth and shoot length were less sensitive. The endpoints with the lowest coefficients of variation were not necessarily the endpoints, which were toxicologically most sensitive. Differences in sensitivity were in the range of 10-1000 for different macrophyte-specific endpoints. No macrophyte species was consistently the most sensitive. Criteria to select endpoints in macrophyte toxicity tests should include toxicological sensitivity, variance and ecological relevance. Hence, macrophyte toxicity tests should comprise an array of endpoints, including very sensitive endpoints like those relating to root growth. - A range of endpoints is more representative of macrophyte fitness than biomass and growth only

Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

Science.gov (United States)

Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

2017-02-05

The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

Various musculoskeletal manifestations of chronic renal insufficiency

International Nuclear Information System (INIS)

Lim, C.Y.; Ong, K.O.

2013-01-01

Musculoskeletal manifestations in chronic renal insufficiency are caused by complex bone metabolism alterations, now described under the umbrella term of chronic kidney disease mineral- and bone-related disorder (CKD-MBD), as well as iatrogenic processes related to renal replacement treatment. Radiological imaging remains the mainstay of disease assessment. This review aims to illustrate the radiological features of CKD-MBD, such as secondary hyperparathyroidism, osteomalacia, adynamic bone disease, soft-tissue calcifications; as well as features associated with renal replacement therapy, such as aluminium toxicity, secondary amyloidosis, destructive spondyloarthropathy, haemodialysis-related erosive arthropathy, tendon rupture, osteonecrosis, and infection

Modeling accumulations of particles in lung during chronic inhalation exposures that lead to impaired clearance

International Nuclear Information System (INIS)

Wolff, R.K.; Griffith, W.C. Jr.; Cuddihy, R.G.; Snipes, M.B.; Henderson, R.F.; Mauderly, J.L.; McClellan, R.O.

1989-01-01

Chronic inhalation of insoluble particles of low toxicity that produce substantial lung burdens of particles, or inhalation of particles that are highly toxic to the lung, can impair clearance. This report describes model calculations of accumulations in lung of inhaled low-toxicity diesel exhaust soot and high-toxicity Ga2O3 particles. Lung burdens of diesel soot were measured periodically during a 24-mo exposure to inhaled diesel exhaust at soot concentrations of 0, 0.35, 3.5, and 7 mg m-3, 7 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y after a 4-wk exposure to 23 mg Ga2O3 m-3, 2 h d-1, 5 d wk-1. Lung burdens of Ga2O3 were measured for 1 y both studies using inhaled radiolabeled tracer particles. Simulation models fit the observed lung burdens of diesel soot in rats exposed to the 3.5- and 7-mg m-3 concentrations of soot only if it was assumed that clearance remained normal for several months, then virtually stopped. Impaired clearance from high-toxicity particles occurred early after accumulations of a low burden, but that from low-toxicity particles was evident only after months of exposure, when high burdens had accumulated in lung. The impairment in clearances of Ga2O3 particles and radiolabeled tracers was similar, but the impairment in clearance of diesel soot and radiolabeled tracers differed in magnitude. This might have been related to differences in particle size and composition between the tracers and diesel soot. Particle clearance impairment should be considered both in the design of chronic exposures of laboratory animals to inhaled particles and in extrapolating the results to people

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

Energy Technology Data Exchange (ETDEWEB)

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.

THE DETERMINATION AND APPRECIATION OF OCCUPATIONAL TOXICITY AT WORK

Directory of Open Access Journals (Sweden)

Oana CHIVU

2017-05-01

Full Text Available The occupational toxins are those chemicals that workers come into contact with during the exercise of the profession and which under certain conditions have harmful effects on the body. The paper aims to address the determination and assessment of occupational toxicities in a workplace with the aim of ensuring an adequate working enviro nment as well as preventing occupational diseases, accidents and chronic fatigue.

THE DETERMINATION AND APPRECIATION OF OCCUPATIONAL TOXICITY AT WORK

OpenAIRE

Oana CHIVU; Claudiu BABIS; Andrei DIMITRESCU

2017-01-01

The occupational toxins are those chemicals that workers come into contact with during the exercise of the profession and which under certain conditions have harmful effects on the body. The paper aims to address the determination and assessment of occupational toxicities in a workplace with the aim of ensuring an adequate working enviro nment as well as preventing occupational diseases, accidents and chronic fatigue.

Toxicogenetics: in search of host susceptibility to environmental toxicants

OpenAIRE

Alam, Gelareh; Jones, Byron C.

2014-01-01

Heavy metals, various pesticide and herbicides are implicated as risk factors for human health. Paraquat, maneb, and rotenone, carbamate, and organophosphorous insecticides are examples of toxicants for which acute and chronic exposure are associated with multiple neurological disorders including Parkinson’s disease. Nevertheless, the role of pesticide exposure in neurodegenerative diseases is not clear-cut, as there are inconsistencies in both the epidemiological and preclinical research. Th...

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

International Nuclear Information System (INIS)

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

2017-01-01

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

MR imaging in solvent-induced chronic toxic encephalopathy

International Nuclear Information System (INIS)

Thuomas, K.AA.; Moeller, C.; Oedkvist, L.M.; Flodin, U.; Dige, N.

1996-01-01

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

Evaluation of Methacholine Challenge Test Results in Chronic Cough Patients Referring to Clinic of Pulmonary Disease

Directory of Open Access Journals (Sweden)

Derakhshan Deilami Gholamreza

2009-10-01

Full Text Available Chronic cough is a common problem in patients visiting physicians and its prevalence in different populations range from 3 to 40%. Postnasal drip, asthma and gastroesophageal reflux are the known cause of chronic cough. Although diagnosis of asthma is usually made by clinical signs and spirometeric results, methacholine challenge test is a good diagnostic test in patients who show normal physical examination and spirometeric results. In this study, the results of methacholine challenge test in chronic cough patients are investigated. This is a cross sectional study performed on patients suffering from chronic cough (over 8 weeks, who went to Pulmonary Disease Clinic of Imam Khomeini Hospital in 2006. Postnasal drip, gastroesophageal reflux was evaluated and ruled out in all patients. Then they were tested by methacholine inhalation using low to high doses of methacholine. The results of test was defined as 20% fall in FEV1 and its relationship with age, sex, history of allergic disease, family history of asthma and smoking status was investigated. 81 patients (36 female and 45 male entered this study who had mean age of 32.5 ± 13.06 years. 81.5% of patients had never smoked or closed contact with smokers, 6.2% were passive smokers, 8.6% were smokers and 3.7% had quit smoking. 37% had suffered from chronic cough less than 6 months, 11% for 6-11 months and 52% for more than 12 months. In 26% of patients, family history of asthma was present and 34.5% had a history of one type of allergy. In 29.5% the results of methacholine challenge test was positive, among them 45.8% showed an intense response and 54.2% a moderate response. The test results and its intensity had no statistically significant relationship with age, sex, smoking status, the duration of cough and family history of asthma, but the relationship between methacholine challenge test and the history of allergic disease was significant. Methacholine challenge test can be used as a

N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

Science.gov (United States)

Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

2016-01-01

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

Alimentary, metabolic and toxic osteopathies in adults

Energy Technology Data Exchange (ETDEWEB)

Ellegast, H.H.

1986-12-01

Skeletal changes in deficient or badly balanced nutrition (alimentary osteopathies) and osseous changes accompanying chronic desease of internal organs and metabolic disorders (metabolic osteopathies) are discussed. Basically, the classical generalised skeletal changes such as osteoporosis, osteomalacia, fibroosteoclacia and sklerosis of the bone can occur in their pure form or as a combination of two or more of these disorders. Finally the exogenic toxic osteopathies are discussed, nowadays fluorosis being the most important. Other external factors may be drugs like methotrexate and antiepileptic medications.

Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

OpenAIRE

Richard Sauerheber

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity ...

Chronic pharmacologic inhibition of EGFR leads to cardiac dysfunction in C57BL/6J mice

International Nuclear Information System (INIS)

Barrick, Cordelia J.; Yu Ming; Chao, H.-H.; Threadgill, David W.

2008-01-01

Molecule-targeted therapies like those against the epidermal growth factor receptor (EGFR) are becoming widely used in the oncology clinic. With improvements in treatment efficacy, many cancers are being treated as chronic diseases, with patients having prolonged exposure to several therapies that were previously only given acutely. The consequence of chronic suppression of EGFR activity may lead to unexpected toxicities like altered cardiac physiology, a common organ site for adverse drug effects. To explore this possibility, we treated C57BL/6J (B6) mice with two EGFR small molecule tyrosine kinase inhibitors (TKIs), irreversible EKB-569 and reversible AG-1478, orally for 3 months. In B6 female mice, chronic exposure to both TKIs depressed body weight gain and caused significant changes in left ventricular (LV) wall thickness and cardiac function. No significant differences were observed in heart weight or cardiomyocyte size but histological analysis revealed an increase in fibrosis and in the numbers of TUNEL-positive cells in the hearts from treated female mice. Consistent with histological results, LV apoptotic gene expression was altered, with significant downregulation of the anti-apoptotic gene Bcl2l1. Although there were no significant differences in any of these endpoints in treated male mice, suggesting sex may influence susceptibility to TKI mediated toxicity, the LVs of treated male mice had significant upregulation of Egf, Erbb2 and Nppb over controls. Taken together, these data suggest that chronic dietary exposure to TKIs may result in pathological and physiological changes in the heart

Absorbable hydrogel spacer use in men undergoing prostate cancer radiotherapy: 12 month toxicity and proctoscopy results of a prospective multicenter phase II trial

International Nuclear Information System (INIS)

Uhl, Matthias; DeWeese, Theodore L; Herfarth, Klaus; Eble, Michael J; Pinkawa, Michael; Triest, Baukelien van; Kalisvaart, Robin; Weber, Damien C; Miralbell, Raymond; Song, Danny Y

2014-01-01

Radiation therapy is one of the recommended treatment options for localized prostate cancer. In randomized trials, dose escalation was correlated with better biochemical control but also with higher rectal toxicity. A prospective multicenter phase II study was carried out to evaluate the safety, clinical and dosimetric effects of the hydrogel prostate-rectum spacer. Here we present the 12 months toxicity results of this trial. Fifty two patients with localized prostate cancer received a transperineal PEG hydrogel injection between the prostate and rectum, and then received IMRT to a dose of 78 Gy. Gastrointestinal and genitourinary toxicity were recorded during treatment and at 3, 6 and 12 months following irradiation by using the RTOG/EORTC criteria. Additionally, proctoscopy was performed 12 months after treatment and the results were scored using the Vienna Rectoscopy Scale (VRS). Of the patients treated 39.6% and 12.5% experienced acute Grade 1 and Grade 2 GI toxicity, respectively. There was no Grade 3 or Grade 4 acute GI toxicity experienced in the study. Only 4.3% showed late Grade 1 GI toxicity, and there was no late Grade 2 or greater GI toxicity experienced in the study. A total of 41.7%, 35.4% and 2.1% of the men experienced acute Grade 1, Grade 2 and Grade 3 GU toxicity, respectively. There was no Grade 4 acute GU toxicity experienced in the study. Late Grade 1 and Grade 2 GU toxicity was experienced in 17.0% and 2.1% of the patients, respectively. There was no late Grade 3 or greater GU toxicity experienced in the study. Seventy one percent of the patients had a VRS score of 0, and one patient (2%) had Grade 3 teleangiectasia. There was no evidence of ulceration, stricture or necrosis at 12 months. The use of PEG spacer gel is a safe and effective method to spare the rectum from higher dose and toxicity

Herbicide toxicity on river biofilms assessed by pulse amplitude modulated (PAM) fluorometry

Energy Technology Data Exchange (ETDEWEB)

Kim Tiam, Sandra, E-mail: sandra.kimtiam@gmail.com [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Laviale, Martin [Departamento de Biologia and CESAM – Centro de Estudos do Ambiente e do Mar Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Sorbonne Universités, UPMC Univ Paris 06, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer (France); CNRS, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer France (France); Feurtet-Mazel, Agnès [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Jan, Gwilherm [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Gonzalez, Patrice [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Mazzella, Nicolas; Morin, Soizic [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France)

2015-08-15

Highlights: • Rapid Light Curves were shown to be early markers of toxicant exposure. • Diuron and norflurazon effects were significant at environmentally realistic concentrations. • Toxic effects in intact biofilms seem to be delayed compared to disrupted biofilms. - Abstract: The use of Rapid light curves (RLCs) as a toxicity endpoint for river biofilms was examined in this study and compared to “classical fluorescence parameters” i.e. minimal fluorescence (F{sub 0}), optimal and effective quantum yields of photosystem II (F{sub v}/F{sub m} and Φ{sub PSII}). Measurements were performed after exposure to five concentrations of diuron (from 0.3 to 33.4 μg L{sup −1}), its main degradation product (DCPMU) (from 1.0 to 1014 μg L{sup −1}) and norflurazon (from 0.6 to 585 μg L{sup −1}) with the lowest exposure concentrations corresponding to levels regularly encountered in chronically contaminated sites. Biofilm responses were evaluated after 1, 5, 7 and 14 days of exposure to the different toxicants. Overall, the responses of both “classical fluorescence parameters” and RLC endpoints were highly time dependent and related to the mode of action of the different compounds. Interestingly, parameters calculated from RLCs (α, ETR{sub max} and I{sub k}) were useful early markers of pesticide exposure since they revealed significant effects of all the tested toxicants from the first day of exposure. In comparison, classical fluorescence endpoints (F{sub 0} and F{sub v}/F{sub m}) measured at day 1 were only affected in the DCPMU treatment. Our results demonstrated the interest of RLCs as early markers of toxicant exposure particularly when working with toxicants with less specific mode of action than PSII inhibitors.

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

African Journals Online (AJOL)

AJL

2012-06-14

Jun 14, 2012 ... Thailand registered PN in the list of herbal medical ... Pharmacy, Silpakorn University, Nakorn Pathom, Thailand. The ... automated blood analyzer (Hitachi Science Systems Ltd., Ibaraki, ..... toxic effects of the extracts in both concurrent control and ..... uric acid levels might be necessary when patients are.

Toxicity evaluation and prediction of toxic chemicals on activated sludge system.

Science.gov (United States)

Cai, Bijing; Xie, Li; Yang, Dianhai; Arcangeli, Jean-Pierre

2010-05-15

The gaps of data for evaluating toxicity of new or overloaded organic chemicals on activated sludge system resulted in the requirements for methodology of toxicity estimation. In this study, 24 aromatic chemicals typically existed in the industrial wastewater were selected and classified into three groups of benzenes, phenols and anilines. Their toxicity on activated sludge was then investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively from the respiration rates of activated sludge with different toxicant concentration at mid-term (24h) and short-term (30min) time intervals. Experimental results showed that the group of benzenes was the most toxic, followed by the groups of phenols and anilines. The values of IC(50-M) of the tested chemicals were higher than those of IC(50-S). In addition, quantitative structure-activity relationships (QSARs) models developed from IC(50-M) were more stable and accurate than those of IC(50-S). The multiple linear models based on molecular descriptors and K(ow) presented better reliability than single linear models based on K(ow). Among these molecular descriptors, E(lumo) was the most important impact factor for evaluation of mid-term toxicity. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Diagnostic efficiency and treatment strategy in chronic axonal polyneuropathy

NARCIS (Netherlands)

Vrancken, A.F.J.E.

2007-01-01

Polyneuropathy is a common peripheral nerve disorder that often has a well known cause such as diabetes, chronic renal disease, alcohol abuse, vitamin deficiency, hypothyroidism, or use of toxic medication. Elderly people are more often affected, but the differentiation from signs of normal ageing

Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals

DEFF Research Database (Denmark)

Achhra, Amit C; Nugent, Melinda; Mocroft, Amanda

2016-01-01

Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted...

Toxicity studies of the water extract from the calyces of Hibiscus ...

African Journals Online (AJOL)

Acute and chronic toxicities of the water extract from calyces of Hibiscus sabdariffa were studied in male and female rats. After 14 days of a single oral administration of test substance 5,000 mg/kg body weight, measurement of the body and organ weights, necropsy and health monitoring were performed. No signs and ...

Toxicity alarm: Case history

International Nuclear Information System (INIS)

Hogan, D.; Retallack, J.

1993-01-01

In late fall 1991, the Novacor petrochemical plant near Joffre, Alberta experienced a toxicity alarm, the first since its startup 14 years ago. Fish exposed to a normal toxicity test were stressed within 2 h and showed 100% mortality after 24 h. A history of the events leading up to, during, and after the toxicity alarm is presented. The major effluent sources were three cooling water systems. Although these sources are well characterized, the event causes were not immediately clear. Initial toxic screening indicated that one was very toxic, another moderately toxic, and the third not toxic at all. All three systems utilized the same chemical treatment program to avoid fouling: stabilized phosphates with minor variants. The most toxic of the cooling systems operated at 10-12 cycles, had three chemicals for biocide control, and had three makeup streams. Toxic and nontoxic system characteristics were compared. An in-depth modified toxicity identification and evaluation program was then performed to identify and evaluate the cause of the toxicity alarm for future prevention. The most probable causes of toxicity were identified by elimination. The combination of high numbers of cycles, hydrocarbons in the makeup water, and bromine added as an antifoulant resulted in formation of aromatic bromamines which are capable of causing the toxic condition experienced. 2 tabs

Modeling Chronic Toxicity: A Comparison of Experimental Variability With (QSAR/Read-Across Predictions

Directory of Open Access Journals (Sweden)

Christoph Helma

2018-04-01

Full Text Available This study compares the accuracy of (QSAR/read-across predictions with the experimental variability of chronic lowest-observed-adverse-effect levels (LOAELs from in vivo experiments. We could demonstrate that predictions of the lazy structure-activity relationships (lazar algorithm within the applicability domain of the training data have the same variability as the experimental training data. Predictions with a lower similarity threshold (i.e., a larger distance from the applicability domain are also significantly better than random guessing, but the errors to be expected are higher and a manual inspection of prediction results is highly recommended.

The surgical treatment of chronic intestinal ischemia: results of a recent series.

Science.gov (United States)

Illuminati, G; Caliò, F G; D'Urso, A; Papaspiropoulos, V; Mancini, P; Ceccanei, G

2004-04-01

Due to the rarity of the condition, large and prospective series defining the optimal method of digestive arteries revascularization, for the treatment of chronic intestinal ischemia, are lacking. The aim of this consecutive sample clinical study was to test the hypothesis that flexible application of different revascularization methods, according to individual cases, will yield the best results in the management of chronic intestinal ischemia. Eleven patients, of a mean age of 56 years, underwent revascularization of 11 digestive arteries for symptomatic chronic mesenteric occlusive disease. Eleven superior mesenteric arteries and one celiac axis were revascularized. The revascularization techniques included retrograde bypass grafting in 7 cases, antegrade bypass grafting in 2, percutaneous arterial angioplasty in 1, and arterial reimplantation in one case. The donor axis for either reimplantation or bypass grafting was the infrarenal aorta in 4 cases, an infrarenal Dacron graft in 4, and the celiac aorta in one case. Grafting materials included 5 polytetrafluoroethylene (PTFE) and 3 Dacron grafts. Concomitant procedures included 3 aorto-ilio-femoral grafts and one renal artery revascularization. Mean follow-up duration was 31 months. There was no operative mortality. Cumulative survival rate was 88.9% at 36 months (SE 12.1%). Primary patency rate was 90% at 36 months (SE 11.6%). The symptom free rate was 90% at 36 months (SE 11.6%). Direct reimplantation, antegrade and retrograde bypass grafting, all allow good mid-term results: the choice of the optimal method depends on the anatomic and general patient's status. Associated infrarenal and renal arterial lesions can be safely treated in the same time of digestive revascularization. Angioplasty alone yields poor results and should be limited to patients at poor risk for surgery.

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

Energy Technology Data Exchange (ETDEWEB)

Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-04-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

International Nuclear Information System (INIS)

Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-01-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

Chronic arsenic poisoning following ayurvedic medication.

Science.gov (United States)

Pinto, Benzeeta; Goyal, Palvi; Flora, S J S; Gill, K D; Singh, Surjit

2014-12-01

Ayurveda, Indian traditional system of medicine, is practiced commonly in South East Asia and in many parts of the world. Many ayurvedic drugs contain heavy metals and may lead to metal toxicity. Of these, chronic lead poisoning is the most common. Chronic arsenic poisoning following the use of ayurvedic medication, though reported, is rare. We describe three patients who presented with features of chronic arsenic poisoning following prolonged ayurvedic medication use. The diagnosis of chronic arsenic poisoning was confirmed by high arsenic levels in the blood, urine, hair, and nails in all the three patients and in ayurvedic drug in two patients. The ayurvedic medication was discontinued and treatment with D-penicillamine started. At 6 months after treatment, blood arsenic levels returned to normal with clinical recovery in all of them. Arsenic poisoning following ayurvedic medication is much less common than lead poisoning, though mineral ayurvedic medicines may lead to it. We used D-penicillamine as chelator and all of them recovered. Whether withdrawal of medication alone or D-penicillamine also played a role in recovery is unclear and needs to be assessed.

Effect of low-dose ionizing radiation on luminous marine bacteria: radiation hormesis and toxicity

International Nuclear Information System (INIS)

Kudryasheva, N.S.; Rozhko, T.V.

2015-01-01

The paper summarizes studies of effects of alpha- and beta-emitting radionuclides (americium-241, uranium-235+238, and tritium) on marine microorganisms under conditions of chronic low-dose irradiation in aqueous media. Luminous marine bacteria were chosen as an example of these microorganisms; bioluminescent intensity was used as a tested physiological parameter. Non-linear dose-effect dependence was demonstrated. Three successive stages in the bioluminescent response to americium-241 and tritium were found: 1 – absence of effects (stress recognition), 2 – activation (adaptive response), and 3 – inhibition (suppression of physiological function, i.e. radiation toxicity). The effects were attributed to radiation hormesis phenomenon. Biological role of reactive oxygen species, secondary products of the radioactive decay, is discussed. The study suggests an approach to evaluation of non-toxic and toxic stages under conditions of chronic radioactive exposure. - Highlights: • Luminous bacteria demonstrate nonlinear dose-effect relation in radioactive solutions. • Response to low-dose radiation includes 3 stages: threshold, activation, inhibition. • ROS are responsible for low-dose effects of alpha-emitting radionuclides. • Luminous marine bacteria are a convenient tool to study radiation hormesis

TOXICITY BEHAVIORS IN ORGANIZATIONS: STUDY OF RELIABILITY AND VALIDITY OF TOXIC EMOTIONAL EXPERIENCES SCALE

OpenAIRE

Bektas, Meral; Erkal, Pinar

2016-01-01

In toxic organizations which are mostly destructive instead of being constrictive towards its employees, toxicity behaviors emerge as a result of the formal and informal relationships. Toxicity behaviors are often negatively affect motivation, job satisfaction or performance of the employees in workplace. Basic toxicity behaviors in organizations are: extreme jealousy, biting words, emphasis  superiority emphasis, getting angry, offending employees, strict control, heavy job workload, limited...

Results of radiosynoviorthesis with yttrium 90 in cases of chronic synovitis

International Nuclear Information System (INIS)

Schuette, H.

1982-01-01

The goal of this study was to answer the following questions: Is the outcome of radiosynoviorthesis with 90 Y in patients who suffer from a chronic polyarthritis dependent on the stage according to Steinbrocker and does this dependency change when the results are measured 1/2 to 3 years later? Is there a difference between the effect of 90 Y on the joints of seropositive and seronegative patients? How are the results of radiosynoviorthesis in patients who suffer under other chronic joint diseases? What is the success distribution of re-synoviorthesis in evaluated patients? Is there a difference in the effectiveness of radiosynoviorthesis between joints in stage I and stage II and is the outcome dependent on whether or not degenerative changes are already present? Is the effect of radiosynoviorthesis, measured after one year, dependent on the duration of the disease in the treated joint or on the process activity of the disease? Is there a connection between the outcome of radiosynoviorthesis and the laboratory parameters of blood sedimentation and hemoglobin content? Does radiosynoviorthesis influence the number of medically induced, intra-articular injections and punctures in the treated joint? Is there a connection between radiosynoviorthesis outcomes and common therapy outcomes? What side effects of radiosynoviorthesis therapy were observed? (orig./MG) [de

Chronic Myeloid Leukemia with Variant Chromosomal Translocations: Results of Treatment with Imatinib Mesylate

Directory of Open Access Journals (Sweden)

Rohan Bhise

2013-01-01

Full Text Available Objective: To evaluate the efficacy of imatinib in chronic myeloid leukemia patients with variant translocations. Methods: Forty eight chronic myeloid leukemia patients carrying variant translocations and treated with imatinib at our institute were considered for the study. Survival and response rates were evaluated. Results: The median follow up was 48 months(m. Forty three (89.58% patients achieved complete hematologic response. Thirty one (64.58% patients achieved complete cytogenetic response and 19(39.58% achieved major molecular response anytime during their follow up period. Only 18.75% of the patients achieved complete cytogenetic response and major molecular response within the stipulated time frames.The estimated overall survival at 48 m median follow up was 81.2%.The progression free survival was also 81.2% and the event free survival was 79.1%.There was no significant survival difference between low vs intermediate and high risk sokal group. Conclusion: We report suboptimal responses to imatinib in chronic myeloid leukemia with variant translocations. Further studies with imatinib and the newer more active drugs dasatinib and nilotinib are justified.

Effect of new soil metal immobilizing agents on metal toxicity to terrestrial invertebrates

Energy Technology Data Exchange (ETDEWEB)

Lock, K.; Janssen, C.R

2003-01-01

Organisms with different exposure routes should be used to simultaneously assess risks of metals in soils. - Application of 5% (w:w) novel metal immobilizing agent reduced the water soluble, the calcium chloride extracted as well as the pore water concentration of zinc in soils from Maatheide, a metal contaminated site in the northeast of Belgium. Addition of the metal immobilizing agents also eliminated acute toxicity to the potworm Enchytraeus albidus and the earthworm Eisenia fetida and chronic toxicity to the springtail Folsomia candida. Cocoon production by E. fetida, however, was still adversely affected. These differences may be explained by the species dependent routes of metal uptake: F. candida is probably mainly exposed via pore water while in E. fetida dietary exposure is probably also important. From these results it is clear that organisms with different exposure routes should be used simultaneously to assess the environmental risk of metal contaminated soils.

[Treatment Strategy and Results of Carotid Endarterectomy in Chronic Renal Failure Patients].

Science.gov (United States)

Murahashi, Takeo; Kamiyama, Kenji; Osato, Toshiaki; Watanabe, Toshiichi; Ogino, Tatsuya; Sugio, Hironori; Endo, Hideki; Takahira, Kazuki; Shindo, Koichiro; Takahashi, Shuhei; Nakamura, Hirohiko

2017-02-01

The number of patients receiving chronic dialysis treatment in Japan currently exceeds 300,000 people. Few reports have described carotid endarterectomy(CEA)for chronic renal failure patients because of the unacceptable rate of perioperative stroke and other morbidities. A strategy for and treatment results of CEA for chronic renal failure patients in our hospital are described herein. The present study included 6 patients who underwent CEA while receiving dialysis treatment between April 2011 and November 2014. Dialysis treatment was initiated due to diabetes in 4 patients and renal sclerosis in 2 patients. All the patients were men, with a mean age of 74.0 years. Two patients were symptomatic, and four were asymptomatic. In all the patients, heart vascular lesions and arteriosclerosis risk factors were present. Postoperatively, pneumonia transient cranial neuropathy, heart failure, and pneumonia in 1 case required extensive treatment. However, by the time of discharge from hospital, no cases had deteriorated compared with their pre-CEA state. The modified Rankin scale score on discharge was 0-2 for all the patients. CEA can be performed safely in patients receiving dialysis, but further operative procedures and careful postoperative management are likely to be needed for patients with CEA who are receiving dialysis.

The association between diabetes mellitus, glucose, and chronic musculoskeletal complaints. Results from the Nord-Trøndelag Health Study

Directory of Open Access Journals (Sweden)

Zwart John-Anker

2008-12-01

Full Text Available Abstract Background The relationship between diabetes mellitus (DM and chronic musculoskeletal complaints (MSCs is unclear. The aim of this study was to investigate the association between DM, non-fasting glucose and chronic MSCs defined as pain and/or stiffness ≥ 3 months during the past year in the general adult population. Methods The results were based on cross-sectional data from 64,785 men and women (aged ≥ 20 years who participated in the Nord-Trøndelag Health Survey, which included 1,940 individuals with known DM. Associations were assessed using multiple logistic regression, estimating prevalence odds ratio (OR with 95% confidence intervals (CIs. Results High non-fasting glucose was associated with a lower prevalence of chronic MSCs compared to a low glucose level. DM was associated with higher prevalence of chronic MSCs, in particular chronic widespread MSCs. In the multivariate analysis, adjusting for glucose level, BMI, age, gender and physical activity, chronic widespread MSCs was 1.6 times more likely (OR = 1.6, 95% CI 1.2–2.2 among individuals Conclusion In this cross-sectional study a high non-fasting glucose was associated with lower prevalence of chronic MSCs. Among individuals with known DM chronic widespread MSCs were more likely.

Alimentary, metabolic and toxic osteopathies in adults

International Nuclear Information System (INIS)

Ellegast, H.H.

1986-01-01

Skeletal changes in deficient or badly balanced nutrition (alimentary osteopathies) and osseous changes accompanying chronic desease of internal organs and metabolic disorders (metabolic osteopathies) are discussed. Basically, the classical generalised skeletal changes such as osteoporosis, osteomalacia, fibroosteoclacia and sklerosis of the bone can occur in their pure form or as a combination of two or more of these disorders. Finally the exogenic toxic osteopathies are discussed, nowadays fluorosis being the most important. Other external factors may be drugs like methotrexate and antiepileptic medications. (orig.) [de

The toxic effects of chlorophenols and associated mechanisms in fish

International Nuclear Information System (INIS)

Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun

2017-01-01

Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

The toxic effects of chlorophenols and associated mechanisms in fish

Energy Technology Data Exchange (ETDEWEB)

Ge, Tingting; Han, Jiangyuan; Qi, Yongmei; Gu, Xueyan; Ma, Lin; Zhang, Chen; Naeem, Sajid; Huang, Dejun, E-mail: huangdj@lzu.edu.cn

2017-03-15

Highlights: • We review the toxic effects of chlorophenols (CPs) and underlying mechanisms in fish. • CPs induce lethal effects, oxidative stress, endocrine disruption, reproductive toxicity and apoptosis in fish. • CPs exhibit toxicity through multiple signaling pathways in fish and different pathways co-exist under the same conditions. • Studies on DNA methylation provide new insights into our understanding of epigenetic mechanisms of CPs-induced toxicity. • Mechanisms studies on CPs toxicity performed under environmental concentrations need more attentions. - Abstract: Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems. CPs affect immune system by altering the number of mature B cells and macrophages, while suppressing phagocytosis and down-regulating the expression of immune factors. CPs also disrupt endocrine function by affecting hormone levels, or inducing abnormal gene expression and interference with hormone receptors. CPs at relatively higher concentrations induce apoptosis via mitochondria-mediated pathway, cell death receptor-mediated pathway, and/or DNA damage-mediated pathway. CPs at relatively lower concentrations promote cell proliferation, and foster cancers-prone environment by increasing the rate of point mutations and oxidative DNA lesions. These toxic effects in fish are induced directly by CPs per se or indirectly by their metabolic products. In addition, recent

Assessment of the toxicity of the Brazilian pepper trees Schinus terebinthifolius Raddi (Aroeira-da-praia) and Myracrodruon urundeuva Allemão (Aroeira-do-sertão).

Science.gov (United States)

Carlini, Elisaldo Araujo; Duarte-Almeida, Joaquim Maurício; Tabach, Ricardo

2013-05-01

The present study aimed to assess the preclinical toxicity of two plants commonly used to treat "stomach ailments" in Brazil: Schinus terebinthifolius Raddi (S) and Myracrodruon urundeuva Allemão (M). In male rats, chronic treatment (83 days) with both pepper trees (17.6 and 13.8 mg/kg, S and M, respectively) has been shown to decrease hematocrit. However, a reduction in the number of red blood cells and hemoglobin was only seen following administration of S. terebinthifolius. None of the plants caused anatomopathological alterations following chronic treatment, and mating ability and fertility were not affected. Both pepper trees showed moderate toxicity following acute and chronic treatment by gavage, particularly S. terebinthifolius. Moreover, bone malformations were induced in fetuses, and a slight delay in recovery time of the postural reflex was observed in pups from female animals treated (18 days) with S. terebinthifolius. Given these results, a better assessment of the risks and benefits of the internal use of these plants is necessary, especially when used by women of childbearing age. Copyright © 2012 John Wiley & Sons, Ltd.

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

Directory of Open Access Journals (Sweden)

Debendranath Dey

2015-01-01

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

Toxicity and bioaccumulation of sediment-associated contaminants using freshwater invertebrates: A review of methods and applications

Science.gov (United States)

Ingersoll, C.G.; Ankley, G.T.; Benoit, D.A.; Brunson, E.L.; Burton, G.A.; Dwyer, F.J.; Hoke, R.A.; Landrum, P.F.; Norberg-King, T. J.; Winger, P.V.

1995-01-01

This paper reviews recent developments in methods for evaluating the toxicity and bioaccumulation of contaminants associated with freshwater sediments and summarizes example case studies demonstrating the application of these methods. Over the past decade, research has emphasized development of more specific testing procedures for conducting 10-d toxicity tests with the amphipod Hyalella azteca and the midge Chironomus tentans. Toxicity endpoints measured in these tests are survival for H. azteca and survival and growth for C. tentans. Guidance has also been developed for conducting 28-d bioaccumulation tests with the oligochaete Lumbriculus variegatus, including determination of bioaccumulation kinetics for different compound classes. These methods have been applied to a variety of sediments to address issues ranging from site assessments to bioavailability of organic and inorganic contaminants using field-collected and laboratory-spiked samples. Survival and growth of controls routinely meet or exceed test acceptability criteria. Results of laboratory bioaccumulation studies with L. variegatus have been confirmed with comparisons to residues (PCBs, PAHs, DDT) present from synoptically collected field populations of oligochaetes. Additional method development is currently underway to develop chronic toxicity tests and to provide additional data-confirming responses observed in laboratory sediment tests with natural benthic populations.

Yellow phosphorus process to convert toxic chemicals to non-toxic products

Science.gov (United States)

Chang, S.G.

1994-07-26

The present invention relates to a process for generating reactive species for destroying toxic chemicals. This process first contacts air or oxygen with aqueous emulsions of molten yellow phosphorus. This contact results in rapid production of abundant reactive species such as O, O[sub 3], PO, PO[sub 2], etc. A gaseous or liquid aqueous solution organic or inorganic chemicals is next contacted by these reactive species to reduce the concentration of toxic chemical and result in a non-toxic product. The final oxidation product of yellow phosphorus is phosphoric acid of a quality which can be recovered for commercial use. A process is developed such that the byproduct, phosphoric acid, is obtained without contamination of toxic species in liquids treated. A gas stream containing ozone without contamination of phosphorus containing species is also obtained in a simple and cost-effective manner. This process is demonstrated to be effective for destroying many types of toxic organic, or inorganic, compounds, including polychlorinated biphenyls (PCB), aromatic chlorides, amines, alcohols, acids, nitro aromatics, aliphatic chlorides, polynuclear aromatic compounds (PAH), dyes, pesticides, sulfides, hydroxyamines, ureas, dithionates and the like. 20 figs.

On the mechanism of nanoparticulate CeO{sub 2} toxicity to freshwater algae

Energy Technology Data Exchange (ETDEWEB)

Angel, Brad M., E-mail: Brad.Angel@csiro.au [Centre for Environmental Contaminants Research, CSIRO Land and Water Flagship, Locked Bag 2007, Kirrawee, NSW 2232 (Australia); Vallotton, Pascal [Digital Productivity Flagship, CSIRO, North Ryde, NSW 1670 (Australia); Apte, Simon C. [Centre for Environmental Contaminants Research, CSIRO Land and Water Flagship, Locked Bag 2007, Kirrawee, NSW 2232 (Australia)

2015-11-15

Highlights: • Nanoparticulate CeO{sub 2} less toxic than micron-sized CeO{sub 2}. • UV light filters prevented ROS generation by CeO{sub 2}. • ROS not toxic mechanism: CeO{sub 2} toxicity was similar in presence and absence of ROS. • Strong sorption of nanoparticulate CeO{sub 2} to Pseudokirchneriella subcapitata in synthetic fresh water. • CeO{sub 2} sorption to cells was prevented and toxicity mitigated in the presence of DOC. - Abstract: The factors affecting the chronic (72-h) toxicity of three nanoparticulate (10–34 nm) and one micron-sized form of CeO{sub 2} to the green alga, Pseudokirchneriella subcapitata were investigated. To characterise transformations in solution, hydrodynamic diameters (HDD) were measured by dynamic light scatter, zeta potential values by electrophoretic mobility, and dissolution by equilibrium dialysis. The protective effects of humic and fulvic dissolved organic carbon (DOC) on toxicity were also assessed. To investigate the mechanisms of algal toxicity, the CytoViva hyperspectral imaging system was used to visualise algal–CeO{sub 2} interactions in the presence and absence of DOC, and the role of reactive oxygen species (ROS) was investigated by ‘switching off’ ROS production using UV-filtered lighting conditions. The nanoparticulate CeO{sub 2} immediately aggregated in solution to HDDs measured in the range 113–193 nm, whereas the HDD and zeta potential values were significantly lower in the presence of DOC. Negligible CeO{sub 2} dissolution over the time course of the bioassay ruled out potential toxicity from dissolved cerium. The nanoparticulate CeO{sub 2} concentration that caused 50% inhibition of algal growth rate (IC50) was in the range 7.6–28 mg/L compared with 59 mg/L for micron-sized ceria, indicating that smaller particles were more toxic. The presence of DOC mitigated toxicity, with IC50s increasing to greater than 100 mg/L. Significant ROS were generated in the nanoparticulate CeO{sub 2

Evaluation of metals, metalloids, and ash mixture toxicity using sediment toxicity testing.

Science.gov (United States)

Stojak, Amber; Bonnevie, Nancy L; Jones, Daniel S

2015-01-01

In December 2008, a release of 4.1 million m(3) of coal ash from the Tennessee Valley Authority Kingston Fossil Plant occurred. Ash washed into the Emory River and migrated downstream into the Clinch and Tennessee Rivers. A Baseline Ecological Risk Assessment evaluated risks to ecological receptors from ash in the river system post-dredging. This article describes the approach used and results from sediment toxicity tests, discussing any causal relationships between ash, metals, and toxicity. Literature is limited in the realm of aquatic coal combustion residue (CCR) exposures and the potential magnitude of effects on benthic invertebrates. Sediment samples along a spectrum of ash content were used in a tiered toxicity testing approach and included a combination of 10 day sediment toxicity acute tests and longer-term, partial life cycle "definitive" tests with 2 species (Hyalella azteca and Chironomus dilutus). Arsenic, and to a lesser extent Se, in the ash was the most likely toxicant causing observed effects in the laboratory toxicity tests. Sites in the Emory River with the greatest statistical and biologically significant effects had As concentrations in sediments twice the probable effects concentration of 33 mg/kg. These sites contained greater than 50% ash. Sites with less than approximately 50% ash in sediments exhibited fewer significant toxic responses relative to the reference sediment in the laboratory. The results discussed here present useful evidence of only limited effects occurring from a worst-case exposure pathway. These results provided a valuable line of evidence for the overall assessment of risks to benthic invertebrates and to other ecological receptors, and were crucial to risk management and development of project remediation goals. © 2014 SETAC.

[Subchronic toxicity test of genetically modified rice with double antisense starch-branching enzyme gene].

Science.gov (United States)

Li, Min; Piao, Jianhua; Yang, Xiaoguang

2010-07-01

To observe the sub-chronic toxic effects of the genetically modified rice with double antisense SBE gene. Based on gender and weight, weanling Wistar rats were randomly sorted into five groups: non-genetically modified rice group (group A), genetically modified rice group (group B), half genetically modified rice group (group C), quarter genetically modified rice group (group D) and AIN-93G normal diet group (group E). Indicators were the followings: body weight, food consumption, blood routine, blood biochemical test, organ weight, bone density and pathological examination of organs. At the middle of the experiment, the percentage of monocyte of female group B was less than that of group E (P 0.05), and no notable abnormity in the pathological examination of main organs (P > 0.05). There were no enough evidence to confirm the sub-chronic toxicity of genetically modified rice on rats.

Toxic metals in tissues of fishes from the Black Sea and associated human health risk exposure.

Science.gov (United States)

Plavan, Gabriel; Jitar, Oana; Teodosiu, Carmen; Nicoara, Mircea; Micu, Dragos; Strungaru, Stefan-Adrian

2017-03-01

The anthropogenic activities in the Black Sea area are responsible for toxic metal contamination of sea food products. In this study, several toxic metals: cadmium, lead, nickel, chromium, and copper were quantified in different tissues (digestive tract, muscle, skeleton, skin) of nine fish species (Neogobius melanostomus, Belone belone, Solea solea, Trachurus mediterraneus ponticus, Sardina pilchardus, Engraulis encrasicolus, Pomatomus saltatrix, Sprattus sprattus, Scorpaena porcus) by using atomic absorption spectrometer with a high-resolution continuum source and graphite furnace technique (HR-CS GF-AAS), and the risk of fish meat consumption by the young human population was evaluated. These metals are used in high amounts in industries located near the coastline such as shipyard construction and industrial plants. Toxic metal accumulation depends on fish feeding behavior, abiotic conditions, metal chemistry, and animal physiology. For instance, cadmium was measured in the muscle of the investigated species and average values of 0.0008-0.0338 mg kg -1 were obtained. The lowest average value of this metal was measured at benthic species N. melanostomus and the highest at the pelagic predator T. mediterraneus ponticus. Generally, the highest metal concentration was measured in the digestive tract that has the role of biofilter for these contaminants. The risk of contamination is significantly reduced by avoiding the consumption of certain fish tissues (digestive tract and skin for copper and skeleton for nickel). An estimation of the dietary metal intake to young consumers was realized for each of the studied species of fish from Romanian, Bulgarian, and Turkish waters, during the period 2001-2014 in order to evaluate the risks of chronic exposure in time due to metal toxicity. This estimation is important for the prevention of chronic exposure due to metal toxicity. Food exposure to studied metals showed a negative trend for Romania, Turkey, and Bulgaria based

FDA toxicity databases and real-time data entry

International Nuclear Information System (INIS)

Arvidson, Kirk B.

2008-01-01

Structure-searchable electronic databases are valuable new tools that are assisting the FDA in its mission to promptly and efficiently review incoming submissions for regulatory approval of new food additives and food contact substances. The Center for Food Safety and Applied Nutrition's Office of Food Additive Safety (CFSAN/OFAS), in collaboration with Leadscope, Inc., is consolidating genetic toxicity data submitted in food additive petitions from the 1960s to the present day. The Center for Drug Evaluation and Research, Office of Pharmaceutical Science's Informatics and Computational Safety Analysis Staff (CDER/OPS/ICSAS) is separately gathering similar information from their submissions. Presently, these data are distributed in various locations such as paper files, microfiche, and non-standardized toxicology memoranda. The organization of the data into a consistent, searchable format will reduce paperwork, expedite the toxicology review process, and provide valuable information to industry that is currently available only to the FDA. Furthermore, by combining chemical structures with genetic toxicity information, biologically active moieties can be identified and used to develop quantitative structure-activity relationship (QSAR) modeling and testing guidelines. Additionally, chemicals devoid of toxicity data can be compared to known structures, allowing for improved safety review through the identification and analysis of structural analogs. Four database frameworks have been created: bacterial mutagenesis, in vitro chromosome aberration, in vitro mammalian mutagenesis, and in vivo micronucleus. Controlled vocabularies for these databases have been established. The four separate genetic toxicity databases are compiled into a single, structurally-searchable database for easy accessibility of the toxicity information. Beyond the genetic toxicity databases described here, additional databases for subchronic, chronic, and teratogenicity studies have been prepared

[Chronic complex tinnitus: therapeutic results of inpatient treatment in a tinnitus clinic].

Science.gov (United States)

Hesse, G; Rienhoff, N K; Nelting, M; Laubert, A

2001-09-01

In-patient treatment of patients with chronic tinnitus is necessary only when these patients have a severe psychosomatic co-morbidity and suffer severely. However this therapeutic approach has to be supervised and evaluated properly. We present data and results of 1841 patients suffering from chronic tinnitus. Due to the severity of the symptom and psycho-neurotic side effects in-patient treatment was necessary. Therapy lasted 5 - 6 weeks, the main aspect was an intensive psychotherapeutic evaluation and stabilisation next to retraining and habituation programmes. Relaxation techniques were taught. Patients suffered from their tinnitus more than six month; 95 % further suffered from hearing-loss, mainly in high frequencies. The study evaluates results of patients from October 1994 until June 2000. Basis of the study was the evaluation of a specific tinnitus-questionnaire (TQ), published by Hallam in the UK and translated by Goebel and Hiller in Germany. Data was recorded at registration in our clinic, 4 - 6 months later during admission and at the end of the therapy. Final data was gained during a special meeting or questioning 6 months after dismissal from the clinic. Patients that suffered most showed the greatest improvement; directly after therapy there was a highly significant improvement in the TQ for an average of 13.01 points. Highly significant improvements were found in all the TQ-subscales respectively. Only 10 % of the patients did not show any improvement at all. Therapy of most severe cases of chronic tinnitus is possible, using an integrated concept of otologic and psychosomatic treatments. With large numbers of patients and sufficient data a thorough and necessary evaluation of this therapy can be achieved.

Aerobic Bioremediation of PAH Contaminated Soil Results in Increased Genotoxicity and Developmental Toxicity

Science.gov (United States)

Chibwe, Leah; Geier, Mitra C.; Nakamura, Jun; Tanguay, Robert L.; Aitken, Michael D.; Simonich, Staci L. Massey

2015-01-01

The formation of more polar and toxic polycyclic aromatic hydrocarbon (PAH) transformation products is one of the concerns associated with the bioremediation of PAH-contaminated soils. Soil contaminated with coal tar (pre-bioremediation) from a former manufactured gas plant (MGP) site was treated in a laboratory scale bioreactor (post-bioremediation) and extracted using pressurized liquid extraction. The soil extracts were fractionated, based on polarity, and analyzed for 88 PAHs (unsubstituted, oxygenated, nitrated, and heterocyclic PAHs). The PAH concentrations in the soil tested, post-bioremediation, were lower than their regulatory maximum allowable concentrations (MACs), with the exception of the higher molecular weight PAHs (BaA, BkF, BbF, BaP, and IcdP), most of which did not undergo significant biodegradation. The soil extract fractions were tested for genotoxicity using the DT40 chicken lymphocyte bioassay and developmental to xicity using the embryonic zebrafish (Danio rerio) bioassay. A statistically significant increase in genotoxicity was measured in the unfractionated soil extract, as well as in four polar soil extract fractions, post-bioremediation (p bioremediation (p bioremediation. The increased toxicity measured post-bioremediation is not likely due to the 88 PAHs measured in this study (including quinones), because most were not present in the toxic polar fractions and/or because their concentrations did not increase post-bioremediation. However, the increased toxicity measured post-bioremediation is likely due to hydroxylated and carboxylated transformation products of the 3- and 4-ring PAHs (PHE, 1MPHE, 2MPHE, PRY, BaA, and FLA) that were most degraded. PMID:26200254

Predicting molybdenum toxicity to higher plants: Estimation of toxicity threshold values

Energy Technology Data Exchange (ETDEWEB)

McGrath, S.P., E-mail: steve.mcgrath@bbsrc.ac.u [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Mico, C.; Zhao, F.J.; Stroud, J.L. [Soil Science Department, Centre for Soils and Ecosystems Function, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Zhang, H.; Fozard, S. [Division of Environmental Science, Lancaster University, Lancaster LA1 4YQ (United Kingdom)

2010-10-15

Four plant species (oilseed rape, Brassica napus L.; red clover, Trifolium pratense L.; ryegrass, Lolium perenne L.; and tomato, Lycopersicon esculentum L.) were tested on ten soils varying widely in soil properties to assess molybdenum (Mo) toxicity. A larger range (66-fold-609-fold) of added Mo concentrations resulting in 50% inhibition of yield (ED{sub 50}) was found among soils than among plant species (2-fold-38-fold), which illustrated that the soils differed widely in the expression of Mo toxicity. Toxicity thresholds based on soil solution Mo narrowed the variation among soils compared to thresholds based on added Mo concentrations. We conclude that plant bioavailability of Mo in soil depends on Mo solubility, but this alone did not decrease the variability in observed toxicity enough to be used in risk assessment and that other soil properties influencing Mo toxicity to plants need to be considered. - Mo toxicity thresholds varied widely in different soils and therefore soil properties need to be taken into account in order to assess the risk of Mo exposure.

[Abnormal metabolism of triglycerides fractions in chronic pancreatitis and results after the operation treatment].

Science.gov (United States)

Diakowska, Dorota; Knast, Witold; Diakowski, Witold; Grabowski, Krzysztof; Szelachowski, Piotr; Pelczar, Piotr

2005-06-01

This study was undertaken to determine how fats digestion processes were damaged due to chronic pancreatitis, and identify, whether lipid metabolism improved after surgical treatment the patients with chronic pancreatitis. Total lipids, triglycerides, diglycerides and free fatty acids levels in serum and stool were analysed, using chemical tests, thin-layer chromatography and electrophoresis of serum lipoproteins. The patients before the operations showed higher total lipids and triglycerides concentrations, and lower concentrations of diglycerides and free fatty acids in stool. These patients had high triglycerides, chylomicrons, VLDL, LDL-CH concentrations, and low-diglycerides, free fatty acids, HDL-CH concentrations in serum. These data were statistically significant. After the operations and substitution therapy it was observed normalization of the total lipids and lipids fractions levels in stool and in serum. Concentrations of LDL-CH and HDL-CH fractions were irregular. We conclude, that these lipids parameters could be used in diagnosing and monitoring the results of chronic pancreatitis surgical treatment.

Effects of functionalized fullerenes on bifenthrin and tribufos toxicity to Daphnia magna: Survival, reproduction, and growth rate.

Science.gov (United States)

Brausch, Kathryn A; Anderson, Todd A; Smith, Philip N; Maul, Jonathan D

2010-11-01

Incorporation of carbon nanomaterials into industrial and consumer products is increasing, yet their impact on aquatic ecosystems alone and in chemical mixtures is largely unknown. Carbon nanomaterials may be found in the aquatic environment as mixtures with pesticides because of their proposed use in agriculture as smart delivery systems and nanosensors. The interaction effects of a functionalized fullerene ([1,2-methanofullerene C₆₀]-61-carboxylic acid) (fC₆₀) at 52.8 µg/L and the hydrophobic pesticides bifenthrin and tribufos were examined. The test organism was Daphnia magna, and response variables included 48-h survival, reproduction (bifenthrin, 70-d; tribufos, 21-d), and 10-d growth. Both pesticides reduced D. magna survival and reproduction (p bifenthrin acute toxicity but did not significantly affect chronic endpoints or growth (p > 0.05). Median lethal concentrations (LC50s), median inhibition concentrations (IC50s) for days surviving, and IC50s for reproduction were 0.86, 0.55, and 0.49 µg/L for bifenthrin; 0.22, 0.39, and 0.77 µg/L for fC₆₀-bifenthrin mix; 6.63, 9.89, and 5.79 µg/L for tribufos; and 9.17, 8.17, and 6.59 µg/L for fC₆₀-tribufos mix. Mixtures did not affect instantaneous growth rate (p > 0.05). These results suggest that fC₆₀ had little effect on pesticide chronic toxicity but influenced acute toxicity. Given the widespread application of nanotechnology, the influence of nanomaterials on environmental contaminants is an important consideration. Thus, our results may be useful in the development and use of nanotechnology in agricultural practices. © 2010 SETAC.

Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

Science.gov (United States)

Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR

Metallothionein provides zinc-mediated protective effects against methamphetamine toxicity in SK-N-SH cells.

Science.gov (United States)

Ajjimaporn, Amornpan; Swinscoe, John; Shavali, Shaik; Govitrapong, Piyarat; Ebadi, Manuchair

2005-11-30

Methamphetamine (METH) is a drug of abuse and neurotoxin that induces Parkinson's-like pathology after chronic usage by targeting dopaminergic neurons. Elucidation of the intracellular mechanisms that underlie METH-induced dopaminergic neuron toxicity may help in understanding the mechanism by which neurons die in Parkinson's disease. In the present study, we examined the role of reactive oxygen species (ROS) in the METH-induced death of human dopaminergic SK-N-SH cells and further assessed the neuroprotective effects of zinc and metallothionein (MT) against METH-induced toxicity in culture. METH significantly increased the production of reactive oxygen species, decreased intracellular ATP levels and reduced the cell viability. Pre-treatment with zinc markedly prevented the loss of cell viability caused by METH treatment. Zinc pre-treatment mainly increased the expression of metallothionein and prevented the generation of reactive oxygen species and ATP depletion caused by METH. Chelation of zinc by CaEDTA caused a significant decrease in MT expression and loss of protective effects of MT against METH toxicity. These results suggest that zinc-induced MT expression protects dopaminergic neurons via preventing the accumulation of toxic reactive oxygen species and halting the decrease in ATP levels. Furthermore, MT may prevent the loss of mitochondrial functions caused by neurotoxins. In conclusion, our study suggests that MT, a potent scavenger of free radicals is neuroprotective against dopaminergic toxicity in conditions such as drug of abuse and in Parkinson's disease.

Toxicity assessment of sediments from three European river basins using a sediment contact test battery

NARCIS (Netherlands)

Tuikka, A.I.; Schmitt, C.; Hoess, S.; Bandow, N; von der Ohe, P.; de Zwart, D.; de Deckere, E.; Streck, G.; Mothes, S.; van Hattum, A.G.M.; Kocan, A.; Brix, R.; Brack, W.; Barcelo, D.; Sormunen, A.; Kukkonen, J.V.K.

2011-01-01

The toxicity of four polluted sediments and their corresponding reference sediments from three European river basins were investigated using a battery of six sediment contact tests representing three different trophic levels. The tests included were chronic tests with the oligochaete Lumbriculus

Hazard-ranking of agricultural pesticides for chronic health effects in Yuma County, Arizona.

Science.gov (United States)

Sugeng, Anastasia J; Beamer, Paloma I; Lutz, Eric A; Rosales, Cecilia B

2013-10-01

With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam-sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk. Copyright © 2013 Elsevier B.V. All rights reserved.

Hazard-Ranking of Agricultural Pesticides for Chronic Health Effects in Yuma County, Arizona

Science.gov (United States)

Sugeng, Anastasia J.; Beamer, Paloma I.; Lutz, Eric A.; Rosales, Cecilia B.

2013-01-01

With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk. PMID:23783270

Oral toxicity study of certain plant extracts containing pyrrolizidine alkaloids.

Science.gov (United States)

Şeremet, Oana Cristina; Bărbuceanu, Florica; Ionică, Floriana Elvira; Margină, Denisa Marilena; GuŢu, Claudia Maria; Olaru, Octavian Tudorel; Ilie, Mihaela; Gonciar, Veaceslav; Negreş, Simona; ChiriŢă, Cornel

2016-01-01

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds which are found in plants. Poisoning caused by these toxins is associated with acute and chronic liver damage. Tussilago farfara (coltsfoot), Petasites hybridus (common butterbur), Senecio vernalis (eastern groundsel) and Symphytum officinale (comfrey) are traditional phytotherapic species, which beside the therapeutic bioactive compounds contain PAs. The aim of the paper was to assess the safety of some dry extracts obtained from these species. For the determination of acute toxicity, Organization for Economic Cooperation and Development (OECD) Guideline No. 423 was used. For the determination of repeated dose oral toxicity, Senecionis vernalis herba and Symphyti radix extracts (250 mg÷kg) were administrated, by gavage, for 28 days, and their effects on animal weight, liver and biliary functions, hepatic tissue and oxidative stress were investigated. After the acute toxicity testing, the dry extracts were placed in the GHS Category V (LD50>5000 mg÷kg, p.o.). For the subacute toxicity testing, no death or any signs of toxicity were observed. Also, no significant differences in biochemical parameters were observed between control and treated groups. The observed histopathological lesions were non-specific and were not consistent with the data reported in the literature for PAs exposure. In conclusion, the administration for 28 days, of the tested extracts, in a dose which correspond to a PAs concentration over the limits imposed in some countries, produced no hepatic and biliary toxic effects. Further studies, extended over a longer period of time, are needed in order to determine the safety of plant extracts containing PAs.

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

DEFF Research Database (Denmark)

Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen

2017-01-01

Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative...... proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33...... proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb...

The application of a weight of evidence approach to compare the quality of coastal sediments affected by acute (Prestige 2002) and chronic (Bay of Algeciras) oil spills

International Nuclear Information System (INIS)

Morales-Caselles, Carmen; Riba, Inmaculada; Sarasquete, Carmen; Valls, T. Angel del

2008-01-01

To evaluate sediment quality in different areas affected by oil spills, a weight of evidence approach was employed by including a complete set of parameters as part of four lines of evidence: sediment contamination, biological effects (including biomarkers) and bioaccumulation under laboratory conditions, toxicity in field conditions and benthic community structure. The methodology was applied to sediments from the Bay of Algeciras (S Spain) chronically impacted by different spills, and the Galician Coast (NW Spain) acutely impacted by an oil spill (Prestige 2002). Results obtained have elucidated the sources and fates of pollutants and the type of risk involved for the ecosystem. Factorial analysis revealed that the main factors were those containing toxicity, chemistry and benthic community variables indicating degradation in Algeciras. It has been demonstrated that the impact associated with chronic event of contamination by oil spills are significantly more dangerous and polluted than those related to acute effects. - Chronic inputs due to the continuous entrance of contaminants result in much more harm to coastal ecosystems than major but precise environmental impacts

Cyclosporine toxicity in immunosuppressed streptozotocin-diabetic nonhuman primates

International Nuclear Information System (INIS)

Wijkstrom, Martin; Kirchhof, Nicole; Graham, Melanie; Ingulli, Elizabeth; Colvin, Robert B.; Christians, Uwe; Hering, Bernhard J.; Schuurman, Henk-Jan

2005-01-01

Streptozotocin (STZ) is widely applied in animal models of insulin-dependent diabetes mellitus. Adverse effects of STZ mainly concern liver and kidney. In nonhuman primates a single 100-150 mg/kg dose invariably induces diabetes with only rare adverse effects. We report one animal with renal failure necessitating sacrifice. Body weight (age) might be a confounding factor, i.e. older animals might be more vulnerable to STZ-related toxicity. We therefore recommended to administer STZ on a mg/m 2 basis and not on a mg/kg basis. In our islet transplantation program nonhuman primates with STZ-induced diabetes received transplants under chronic immunosuppression including calcineurin inhibitors (cyclosporine, tacrolimus), drugs in the rapamycin class affecting growth factor-induced cell proliferation, and the sphingosine 1-phosphate receptor antagonist FTY720. Four animals developed renal failure and had to be sacrificed, most likely caused by cyclosporine. Kidney histology was typical for cyclosporine toxicity including thrombotic microangiopathy in glomeruli and fibrinoid necrosis of arteries, and for STZ toxicity including acute tubular necrosis and accumulations of erythroid precursors. This adverse effect was observed at a pharmacologically active cyclosporine exposure. Additionally, six diabetic animals without major adverse effects during cyclosporine or tacrolimus treatment are presented. We conclude that cyclosporine facilitates renal dysfunction in animals with STZ-induced diabetes, presumably related to an increased vulnerability to a toxic insult after STZ administration

Materials safety data sheets: the basis for control of toxic chemicals

Energy Technology Data Exchange (ETDEWEB)

Bolton, N. E.; Ketchen, E. E.; Porter, W. E.; Hunt, C. L.

1977-05-01

For large industrial and research operations, maintaining reasonable control of all toxic materials used in their operations can be a formidable task. A system utilizing cards has been developed that serves a dual purpose, informing the user regarding hazards of a particular material and also facilitating appropriate workplace surveillance during its use. Selected data, including threshold limit values, routes of absorption, symptoms of exposure, chronic effects, and emergency first-aid procedures, are printed on the card. A portion of the card contains the label that the user detaches and affixes to the container. This label classifies the material according to flammability, toxicity, reactivity, and special properties on a 0 through 4 hazard rating system. This report describes the development and use of such cards, contains the associated Toxic Material Data Sheets that provide full backup data for the labels, and furnishes a glossary of biomedical terms used in the Data Sheets.

Health Effects of Chronic Arsenic Exposure

Directory of Open Access Journals (Sweden)

Young-Seoub Hong

2014-09-01

Full Text Available Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.

Subchronic and acute preclinical toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae)

International Nuclear Information System (INIS)

Garcia Gonzalez, Mildred; Coto Morales, Teresita; Ocampo, Rafael; Pazos, Liliana

2006-01-01

The effects of the aqueous extract of Petiveria alliacea, leaves were tested on acute and sub-chronic toxicity, hematocrit and blood glucose level and intestinal motility of male albino NGP mice, of 20 to 25 g mean weight. Treatments were in all cases doses of 1000 and 2000 mg/kg animal weight and a control treatment with 0.5 ml distilled water, using 10 animals per treatment and administered orally every day (5 days per week). Experimental periods were 18 and 70 days for acute and sub chronic toxicity, respectively. No mortality nor any toxicity signs could be observed in both tests. A slight but significant increase in the glucose levels during the first three weeks was observed with the 1000 mg/kg dose but not for the higher 2000 mg/kg doses. After administering the dose once after a starving period of six hours, no significant differences in intestinal motility could be found. (author) [es

Subchronic and acute preclinic toxicity and some pharmacological effects of the water extract from leaves of Petiveria alliacea (Phytolaccaceae).