On line biomonitors used as a tool for toxicity reduction evaluation of in situ groundwater remediation techniques.

PubMed

Küster, Eberhard; Dorusch, Falk; Vogt, Carsten; Weiss, Holger; Altenburger, Rolf

2004-07-15

Success of groundwater remediation is typically controlled via snapshot analysis of selected chemical substances or physical parameters. Biological parameters, i.e. ecotoxicological assays, are rarely employed. Hence the aim of the study was to develop a bioassay tool, which allows an on line monitoring of contaminated groundwater, as well as a toxicity reduction evaluation (TRE) of different remediation techniques in parallel and may furthermore be used as an additional tool for process control to supervise remediation techniques in a real time mode. Parallel testing of groundwater remediation techniques was accomplished for short and long time periods, by using the energy dependent luminescence of the bacterium Vibrio fischeri as biological monitoring parameter. One data point every hour for each remediation technique was generated by an automated biomonitor. The bacteria proved to be highly sensitive to the contaminated groundwater and the biomonitor showed a long standing time despite the highly corrosive groundwater present in Bitterfeld, Germany. The bacterial biomonitor is demonstrated to be a valuable tool for remediation success evaluation. Dose response relationships were generated for the six quantitatively dominant groundwater contaminants (2-chlortoluene, 1,2- and 1,4-dichlorobenzene, monochlorobenzene, ethylenbenzene and benzene). The concentrations of individual volatile organic chemicals (VOCs) could not explain the observed effects in the bacteria. An expected mixture toxicity was calculated for the six components using the concept of concentration addition. The calculated EC(50) for the mixture was still one order of magnitude lower than the observed EC(50) of the actual groundwater. The results pointed out that chemical analysis of the six most quantitative substances alone was not able to explain the effects observed with the bacteria. Thus chemical analysis alone may not be an adequate tool for remediation success evaluation in terms of toxicity reduction.

Decolorization of different textile dyes by Penicillium simplicissimum and toxicity evaluation after fungal treatment

PubMed Central

Bergsten-Torralba, L.R.; Nishikawa, M.M.; Baptista, D.F.; Magalhães, D.P.; da Silva, M.

2009-01-01

The objective of this study was to investigate the capacity of decolorization and detoxification of the textile dyes Reactive Red 198 (RR198), Reactive Blue 214 (RB214), Reactive Blue 21 (RB21) and the mixture of the three dyes (MXD) by Penicillium simplicissimum INCQS 40211. The dye RB21, a phthalocyanine, was totally decolorized in 2 days, and the others, the monoazo RR198, the diazo RB214 and MXD were decolorized after 7 days by P. simplicissimum. Initially the dye decolorization involved dye adsorption by the biomass followed by degradation. The acute toxicity after fungal treatment was monitored with the microcrustacean Daphnia pulex and measured through Effective Concentration 50% (EC50). P. simplicissimum reduced efficiently the toxicity of RB21 from moderately acutely toxic to minor acutely toxic and it also reduced the toxicity of RB214 and MXD, which remained minor acutely toxic. Nevertheless, the fungus increased the toxicity of RR198 despite of the reduction of MXD toxicity, which included this dye. Thus, P. simplicissimum INCQS 40211 was efficient to decolorize different textile dyes and the mixture of them with a significant reduction of their toxicity. In addition this investigation also demonstrated the need of toxicological assays associated to decolorization experiments. PMID:24031428

Toxic materials, fishing, and environmental variation: simulated effects on striped bass population trends

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goodyear, C.P.

1985-01-01

Decreased survival of larval striped bass Morone saxatilis resulting from toxic chemicals in the environment and decreased survival of adults caused by fishing both are suspected as agents contributing to the decline in the Chesapeake Bay stock since the mid-1970s. The relative power of each type of mortality to cause population declines was evaluated with simulation techniques. Equivalent levels of added mortality induced qualitatively identical and quantitatively similar trends in population simulations for all conditions examined except if strong density-dependent mortality preceded the contaminant toxicity. In this case the contaminant effect caused a greater reduction in yield, but the populationmore » did not tend toward extinction. The results indicate that the observed downward trend in the Chesapeake Bay population can be halted or reversed by a reduction in fishing mortality, even if contaminant toxicity is the proximate cause for the decline. 28 references, 1 figure, 1 table.« less

Efficacy and toxicological studies of cremophor EL free alternative paclitaxel formulation.

PubMed

Utreja, Puneet; Jain, Subheet; Yadav, Subodh; Khandhuja, K L; Tiwary, A K

2011-11-01

In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated. Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect™ 96-well cell transformation assay. In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation. The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.

Toxicity decrease in urban wastewaters treated by a new biofiltration process.

PubMed

Binelli, A; Magni, S; Della Torre, C; Parolini, M

2015-12-15

We carried out a project aimed to evaluate the possible role played by the freshwater zebra mussel (Dreissena polymorpha) in the possible decrease of some environmental pollutants recalcitrant to tradition wastewater treatments. By the help of a pilot-plant built in the largest wastewater treatment plant of Milan (Italy), we tested several waste mixtures in order to measure the chemicals' abatement made by mussels' biofiltration. This study represents the last step of the wider project and it aimed to evaluate if the decrease in the concentration of some urban pollutants measured in wastewaters was followed by a corresponding toxicity reduction. Thus, we performed 7-day exposures under laboratory conditions to test the toxicity of the raw wastewaters and those preliminary filtered by zebra mussels, through the measurement of different end-points of acute and chronic toxicity. Results showed a clear positive effect of mussels' biofiltration mainly to decrease the acute toxicity made by the two tested wastewater mixtures, while the biomarkers' suite used to evaluate the chronic toxicity showed contradictory results. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of dredged material proposed for ocean disposal from Arthur Kill Project Area, New York

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gruendell, B.D.; Barrows, E.S.; Borde, A.B.

1997-01-01

The objective of the bioassay reevaluation of Arthur Kill Federal Project was to reperform toxicity testing on proposed dredged material following current ammonia reduction protocols. Arthur Kill was one of four waterways sampled and evaluated for dredging and disposal in April 1993. Sediment samples were recollected from the Arthur Kill Project areas in August 1995. Tests and analyses were conducted according to the manual developed by the USACE and the U.S. Environmental Protection Agency (EPA), Evaluation of Dredged Material Proposed for Ocean Disposal (Testing Manual), commonly referred to as the {open_quotes}Green Book,{close_quotes} and the regional manual developed by the USACE-NYDmore » and EPA Region II, Guidance for Performing Tests on Dredged Material to be Disposed of in Ocean Waters. The reevaluation of proposed dredged material from the Arthur Kill project areas consisted of benthic acute toxicity tests. Thirty-three individual sediment core samples were collected from the Arthur Kill project area. Three composite sediments, representing each reach of the area proposed for dredging, was used in benthic acute toxicity testing. Benthic acute toxicity tests were performed with the amphipod Ampelisca abdita and the mysid Mysidopsis bahia. The amphipod and mysid benthic toxicity test procedures followed EPA guidance for reduction of total ammonia concentrations in test systems prior to test initiation. Statistically significant acute toxicity was found in all Arthur Kill composites in the static renewal tests with A. abdita, but not in the static tests with M. bahia. Statistically significant acute toxicity and a greater than 20% increase in mortality over the reference sediment was found in the static renewal tests with A. abdita. M. bahia did not show statistically significant acute toxicity or a greater than 10% increase in mortality over reference sediment in static tests. 5 refs., 2 figs., 2 tabs.« less

Relative toxicity of pyrolysis products of some materials used in home furnishings

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Furst, A.

1976-01-01

Seventy samples of cushioning and upholstery materials used in home furnishings were evaluated for relative toxicity by means of the USF/NASA toxicity screening test. The materials were variably toxic under pyrolysis conditions, and this test appeared suitable for discriminating among them on the bases of time to incapacitation and time to death. The addition of fire retardants to these materials to comply with flammability regulations either had no significant effect on toxicity, or resulted in a reduction in relative toxicity. The modification of materials to comply with California upholstered furniture flammability regulations appears to have resulted in desirable limitations on toxicity. Fifty percent of the 70 materials tested caused incapacitation earlier than did the materials in compliance, and 30 percent caused death earlier.

Silica micro- and nanoparticles reduce the toxicity of surfactant solutions.

PubMed

Ríos, Francisco; Fernández-Arteaga, Alejandro; Fernández-Serrano, Mercedes; Jurado, Encarnación; Lechuga, Manuela

2018-04-20

In this work, the toxicity of hydrophilic fumed silica micro- and nanoparticles of various sizes (7 nm, 12 nm, and 50 μm) was evaluated using the luminescent bacteria Vibrio fischeri. In addition, the toxicity of an anionic surfactant solution (ether carboxylic acid), a nonionic surfactant solution (alkyl polyglucoside), and a binary (1:1) mixture of these solutions all containing these silica particles was evaluated. Furthermore, this work discusses the adsorption of surfactants onto particle surfaces and evaluates the effects of silica particles on the surface tension and critical micellar concentration (CMC) of these anionic and nonionic surfactants. It was determined that silica particles can be considered as non-toxic and that silica particles reduce the toxicity of surfactant solutions. Nevertheless, the toxicity reduction depends on the ionic character of the surfactants. Differences can be explained by the different adsorption behavior of surfactants onto the particle surface, which is weaker for nonionic surfactants than for anionic surfactants. Regarding the effects on surface tension, it was found that silica particles increased the surface activity of anionic surfactants and considerably reduced their CMC, whereas in the case of nonionic surfactants, the effects were reversed. Copyright © 2018 Elsevier B.V. All rights reserved.

[Are acute toxicity testing and the three Rs rule reconcilable? Example of the lethal dose 50 determination].

PubMed

Dorandeu, Fr; Lallement, G

2003-11-01

Toxicity assessment and demonstration of innocuousness of chemical compounds have been part of the research studies conducted in the fields of pharmacy, agriculture and chemical industry for years. Acute systemic toxicity studies are an important element of the safety evaluation. They remain compulsory for regulatory purposes and important for the public opinion that does not accept the risk anymore. Evolutions of the ethics in animal experiments foster a necessary reduction of the number of animals involved in this type of experiments, following the well-known principle of the three Rs rule of Russell and Burch (1959) (Reduction, refinement and replacement). These two views seem in contradiction. Using the example of acute toxicity testing and focusing on the now very criticized parameter lethal dose 50, we will present approaches, including statistical ones, that a toxicologist can use, when free to choose, to keep on conducting the indispensable in vivo studies while abiding by ethical recommendations.

Ecotoxicity assessment of artificial groundwater recharge with reclaimed water: a pilot-scale study.

PubMed

Zhang, Xue; Zhao, Xuan

2013-11-01

A demonstration of artificial groundwater recharge with tertiary effluent was evaluated using a set of bioassays (acute toxicity to Daphnia, genotoxicity, estrogenic and antiestrogenic toxicity). Around 95 % genotoxicity and 53 % antiestrogenicity were removed from the feed water by ozonation, whereas significant reduction of acute toxicity to Daphnia magna was achieved during a 3 days vadose soil treatment. The toxicity was further removed to the same level as the local groundwater during a 20 days aquifer soil treatment. The pilot study has shown that ozonation and soil treatments can improve the quality of municipal wastewater treatment plant effluents for possible groundwater recharge purposes.

Evaluation of dredged material proposed for ocean disposal from Hackensack River Project Area, New York

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gruendell, B.D.; Barrows, E.S.; Borde, A.B.

1997-01-01

The objective of the bioassay reevaluation of the Hackensack River Federal Project was to reperform toxicity testing on proposed dredged material with current ammonia reduction protocols. Hackensack River was one of four waterways sampled and evaluated for dredging and disposal in April 1993. Sediment samples were re-collected from the Hackensack River Project area in August 1995. Tests and analyses were conducted according to the manual developed by the USACE and the U.S. Environmental Protection Agency (EPA), Evaluation of Dredged Material Proposed for Ocean Disposal (Testing Manual), commonly referred to as the {open_quotes}Green Book,{close_quotes} and the regional manual developed by themore » USACE-NYD and EPA Region II, Guidance for Performing Tests on Dredged Material to be Disposed of in Ocean Waters. The reevaluation of proposed dredged material from the Hackensack River project area consisted of benthic acute toxicity tests. Thirty-three individual sediment core samples were collected from the Hackensack River project area. Three composite sediments, representing each reach of the area proposed for dredging, were used in benthic acute toxicity testing. Benthic acute toxicity tests were performed with the amphipod Ampelisca abdita and the mysid Mysidopsis bahia. The amphipod and mysid benthic toxicity test procedures followed EPA guidance for reduction of total ammonia concentrations in test systems prior to test initiation. Statistically significant acute toxicity was found in all three Hackensack River composites in the static renewal tests with A. abdita, but not in the static tests with M. bahia. Statistically significant acute toxicity and a greater than 20% increase in mortality over the reference sediment was found in the static renewal tests with A. abdita. Statistically significant mortality 10% over reference sediment was observed in the M. bahia static tests. 5 refs., 2 figs., 2 tabs.« less

Is the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) a potential alternative for the fish acute toxicity test?

PubMed

Lammer, E; Carr, G J; Wendler, K; Rawlings, J M; Belanger, S E; Braunbeck, Th

2009-03-01

The fish acute toxicity test is a mandatory component in the base set of data requirements for ecotoxicity testing. The fish acute toxicity test is not compatible with most current animal welfare legislation because mortality is the primary endpoint and it is often hypothesized that fish suffer distress and perhaps pain. Animal alternative considerations have also been incorporated into new European REACH regulations through strong advocacy for the reduction of testing with live animals. One of the most promising alternative approaches to classical acute fish toxicity testing with live fish is the fish embryo toxicity (FET) test. The FET has been a mandatory component in routine whole effluent testing in Germany since 2005 and has already been standardized at the international level. In order to analyze the applicability of the FET also in chemical testing, a comparative re-evaluation of both fish and fish embryo toxicity data was carried out for a total of 143 substances, and statistical approaches were developed to evaluate the correlation between fish and fish embryo toxicity data. Results confirm that fish embryo tests are neither better nor worse than acute fish toxicity tests and provide strong scientific support for the FET as a surrogate for the acute fish toxicity test.

Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

PubMed

Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

2017-05-01

Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

Evaluation of the biodegradability and toxicity of landfill leachates after pretreatment using advanced oxidative processes.

PubMed

da Costa, Fabio Moraes; Daflon, Sarah Dario Alves; Bila, Daniele Maia; da Fonseca, Fabiana Valeria; Campos, Juacyara Carbonelli

2018-06-01

Leachate from urban solid waste landfills is a complex mixture of organic and inorganic substances that cause damage to the environment, due to the high concentration of recalcitrant organic matter and toxicity. The objective of this study was to apply advanced oxidation processes (AOP), namely the dark Fenton and solar photo-Fenton processes, to young and old landfill leachates prior to biological treatment. The leachates were obtained from the Seropedica and Gramacho landfill sites, respectively, located in Rio de Janeiro State, Brazil. For the two Fenton processes, different conditions of pH (1.5, 3.0 and 5.0) and Fe 2+ : H 2 O 2 ratio (1:2, 1:5 and 1:10) were evaluated. Biodegradability was evaluated using the Zahn-Wellens methodology and Aliivibrio fischeri acute toxicity tests were conducted in order to predict the toxicity in the activated sludge. The best conditions for both Fenton processes were pH of 3.0 and Fe 2+ : H 2 O 2 and COD RAW :H 2 O 2 mass ratios of 1:5 and 1:1, respectively. The solar photo-Fenton process was more effective at improving the quality for both leachates, reaching COD, TOC and abs 254 nm reductions of 82%, 85% and 96.3%, respectively, for the Seropedica landfill leachate. In the case of the Gramacho landfill leachate, the corresponding reductions were 78.2, 80.7% and 91.1%, respectively. The biodegradability results for the untreated leachates from the Seropedica and Gramacho sites were 65% and 30% respectively. The biodegradability of both leachates was improved by the Fenton processes, especially the solar photo-Fenton process, which increased the leachate biodegradability to 89% (Seropedica) and 69% (Gramacho). For both leachates, a greater reduction in the acute toxicity was achieved with the solar photo-Fenton compared to the dark-Fenton process. The Seropedica landfill leachate showed high toxicity (EC50 = 33%, 15 min), after the dark Fenton and solar photo Fenton processes, with EC50 values of 81 and 91%, respectively. In the case of Gramacho landfill leachate toxicity, the EC50 value of the raw leachate was 13%, whereas after the dark Fenton and solar photo Fenton processes the corresponding values were 54% and 59%, respectively. These results indicate that the Fenton process (especially solar photo-Fenton), was efficient in terms of increasing the biodegradability and reducing the toxicity of the leachate. This is important in relation to protecting the microbiological community in the activated sludge process. Copyright © 2018 Elsevier Ltd. All rights reserved.

Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

PubMed

Dervisis, Nikolaos G; Dominguez, Pedro A; Newman, Rebecca G; Cadile, Casey D; Kitchell, Barbara E

2011-01-01

Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

Environmental lead toxicity: Nutrition as a component of intervention

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahaffey, K.R.

The influence of nutritional status on susceptibility to the toxicity of lead is discussed. Emphasis is given to dietary factors of substantial clinical importance. Subtle changes in susceptibility are difficult to evaluate under conditions of overwhelming lead exposure. It is clear that subtle effects of lead exposure on neurobehavioral and cognitive development are a major concern. The role of nutrition is considered to be an adjunct to reduction of environmental lead exposure, which is the primary means of reducing adverse health effects of lead. Nutrition should be evaluated as a component of strategies to address this broad societal issue.

Pathophysiology and Toxicokinetic Studies of Blue-Green Algae Intoxication in the Swine Model

DTIC Science & Technology

1987-08-31

bovine aer, albamin caused similar reductions !u toxicity, suggesting nonspecific protein binding. Saturation at the N-methyldehydroalanine of MCYST-A...need to conserve toxin and the goal of creating a model for naturally occurring toxicosis caused us to evaluate the oral administration of microcystin...the isolated ileal loop preparation. Pancreatic enzymes and protein-binding were examined as 2 possible causes for the low oral toxicity of MCYST-A

Resolving the false-negative issues of the nonpolar organic amendment in whole-sediment toxicity identification evaluations.

PubMed

Mehler, W Tyler; Keough, Michael J; Pettigrove, Vincent

2018-04-01

Three common false-negative scenarios have been encountered with amendment addition in whole-sediment toxicity identification evaluations (TIEs): dilution of toxicity by amendment addition (i.e., not toxic enough), not enough amendment present to reduce toxicity (i.e., too toxic), and the amendment itself elicits a toxic response (i.e., secondary amendment effect). One such amendment in which all 3 types of false-negatives have been observed is with the nonpolar organic amendment (activated carbon or powdered coconut charcoal). The objective of the present study was to reduce the likelihood of encountering false-negatives with this amendment and to increase the value of the whole-sediment TIE bioassay. To do this, the present study evaluated the effects of various activated carbon additions to survival, growth, emergence, and mean development rate of Chironomus tepperi. Using this information, an alternative method for this amendment was developed which utilized a combination of multiple amendment addition ratios based on wet weight (1%, lower likelihood of the secondary amendment effect; 5%, higher reduction of contaminant) and nonconventional endpoints (emergence, mean development rate). This alternative method was then validated in the laboratory (using spiked sediments) and with contaminated field sediments. Using these multiple activated carbon ratios in combination with additional endpoints (namely, emergence) reduced the likelihood of all 3 types of false-negatives and provided a more sensitive evaluation of risk. Environ Toxicol Chem 2018;37:1219-1230. © 2017 SETAC. © 2017 SETAC.

Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Methods and Materials: Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractionsmore » were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. Results: The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. Conclusions: Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.« less

Toxicity and biocompatibility profile of 3D bone scaffold developed by Universitas Indonesia: A preliminary study

NASA Astrophysics Data System (ADS)

Rahyussalim A., J.; Kurniawati, T.; Aprilya, D.; Anggraini, R.; Ramahdita, Ghiska; Whulanza, Yudan

2017-02-01

Scaffold as a biomaterial must fulfill some requirements to be safely implanted to the human body. Toxicity and biocompatibility test are needed to evaluate scaffold material in mediating cell proliferation and differentiation, secreting extracelullar matrix and carrying biomolecular signals for cell communication. An in vitro study with mesenchymal stem cells consisted of direct contact test and indirect contact test using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay was conducted on 4 scaffolds made of poly-L-lactic acid (PLA), polyvinyl alcohol (PVA), and hydroxyapatite-poly (vinyl alcohol) composite. There were cells-substrate adhesion impairment, morphological changes, cell death and reduction in cell proliferation seen at 2nd and 6th day in most tested scaffold. Cell count result at day-6 showed proliferation inhibition of more than 50% cell death (inhibition value >50) in all tested scaffold. In MTT assay, two scaffolds were proven non-toxic. In conclusion, various scaffold materials showed different toxicity effect. The toxicity and biocompatibility profile in this study is a preliminary data for further research aiming to use those local-made scaffolds to fill human bone defect in various needs.

Solar photocatalytic treatment of quinolones: intermediates and toxicity evaluation.

PubMed

Sirtori, Carla; Zapata, Ana; Malato, Sixto; Gernjak, Wolfgang; Fernández-Alba, Amadeo R; Agüera, Ana

2009-05-01

In this study, degradation of Flumequine (FLU) and nalidixic acid (NXA) in distilled water by two solar photocatalytic processes, TiO(2) and photo-Fenton, was evaluated. Intermediates and acute toxicity of the photoproducts generated were also studied. Degradation efficiency by heterogeneous photocatalysis with TiO(2) was similar for NXA and FLU, which were completely degraded after 25 min of illumination. Less NXA mineralisation was reached after 80 min of illumination. Photo-Fenton degradation of both substances was very quick (<25 min of illumination time), and the same mineralisation was reached in both cases. The kinetic parameters of the two substances were calculated for comparison of their photocatalytic degradation. In all cases, photocatalytic processes were associated with a reduction in toxicity, as evaluated by Vibrio fischeri bioassay. Furthermore, a sharp decrease in inhibition was observed from the beginning of the treatment, even when FLU and NXA were still present in the reaction solution (first samples). These results demonstrate that in both photocatalytic processes studied, toxicity decreases significantly, producing a phototreated sample within safe toxicity limits. The intermediates formed during photocatalytic degradation were studied by liquid chromatography-time of flight-mass spectrometry (LC-TOF-MS).

Toxicity reduction of photo processing wastewaters

USGS Publications Warehouse

Wang, W.

1992-01-01

The photo processing industry can be characterized by treatment processes and subsequent silver recovery. The effluents generated all contain various amounts of silver. The objectives of this study were to determine toxicity of photo processing effluents and to explore their toxicity mitigation. Six samples, from small shops to a major photo processing center, were studied. Two samples (I and VI) were found to be extremely toxic, causing 100 and 99% inhibition of duckweed frond reproduction, respectively, and were used for subsequent toxicity reduction experiments. Lime and sodium sulfide were effective for the toxicity reduction of Sample VI; both reduced its toxicity to negligible. Sample I was far more toxic and was first diluted to 2.2% and then treated with 0.5 g lime/100 mL, reducing toxicity from 100% to 12% inhibition.

Influence of ozonation and biodegradation on toxicity of industrial textile wastewater.

PubMed

Paździor, Katarzyna; Wrębiak, Julita; Klepacz-Smółka, Anna; Gmurek, Marta; Bilińska, Lucyna; Kos, Lech; Sójka-Ledakowicz, Jadwiga; Ledakowicz, Stanisław

2017-06-15

The textile industry demands huge volumes of high quality water which converts into wastewater contaminated by wide spectrum of chemicals. Estimation of textile wastewater influence on the aquatic systems is a very important issue. Therefore, closing of the water cycle within the factories is a promising method of decreasing its environmental impact as well as operational costs. Taking both reasons into account, the aim of this work was to establish the acute toxicity of the textile wastewater before and after separate chemical, biological as well as combined chemical-biological treatment. For the first time the effects of three different combinations of chemical and biological methods were investigated. The acute toxicity analysis were evaluated using the Microtox ® toxicity test. Ozonation in two reactors of working volume 1 dm 3 (stirred cell) and 20 dm 3 (bubble column) were tested as chemical process, while biodegradation was conducted in two, different systems - Sequence Batch Reactors (SBR; working volume 1.5 dm 3 ) and Horizontal Continuous Flow Bioreactor (HCFB; working volume 12 dm 3 ). The untreated wastewater had the highest toxicity (EC50 value in range: 3-6%). Ozonation caused lower reduction of the toxicity than biodegradation. In the system with SBR the best results were obtained for the biodegradation followed by the ozonation and additional biodegradation - 96% of the toxicity removal. In the second system (with HCFB) two-stage treatment (biodegradation followed by the ozonation) led to the highest toxicity reduction (98%). Copyright © 2016 Elsevier Ltd. All rights reserved.

The toxicological properties of petroleum gases.

PubMed

McKee, Richard H; Herron, Deborah; Saperstein, Mark; Podhasky, Paula; Hoffman, Gary M; Roberts, Linda

2014-01-01

To characterize the toxicological hazards of petroleum gases, 90-day inhalation toxicity (Organization for Economic Cooperation and Development [OECD] 413) and developmental toxicity (OECD 414) tests were conducted with liquefied propane gas (LPG) at concentrations of 1000, 5000, or 10,000 ppm. A micronucleus test (OECD 474) of LPG was also conducted. No systemic or developmental effects were observed; the overall no observed adverse effect concentration (NOAEC) was 10,000 ppm. Further, there was no effect of LPG exposure at levels up to 10,000 ppm on micronucleus induction and no evidence of bone marrow toxicity. Other alkane gases (ethane, propane, n-butane, and isobutane) were then evaluated in combined repeated exposure studies with reproduction/development toxicity screening tests (OECD 422). There were no toxicologically important changes in parameters relating to systemic toxicity or neurotoxicity for any of these gases at concentrations ranging from 9000 to 16,000 ppm. There was no evidence of effects on developmental or reproductive toxicity in the studies of ethane, propane, or n-butane at the highest concentrations tested. However, there was a reduction in mating in the high-exposure group (9000 ppm) of the isobutane study, which although not significantly different was outside the range previously observed in the testing laboratory. Assuming the reduction in mating to have been toxicologically significant, the NOAEC for the isobutane reproductive toxicity screening test was 3000 ppm (7125 mg/m(3)). A method is proposed by which the toxicity of any of the 106 complex petroleum gas streams can be estimated from its composition.

Effect of zeolite on toxicity of ammonia in freshwater sediments: Implications for toxicity identification evaluation procedures

USGS Publications Warehouse

Besser, J.M.; Ingersoll, C.G.; Leonard, E.N.; Mount, D.R.

1998-01-01

Techniques for reducing ammonia toxicity in freshwater sediments were investigated as part of a project to develop toxicity identification and evaluation (TIE) procedures for whole sediments. Although ammonia is a natural constituent of freshwater sediments, pollution can lead to ammonia concentrations that are toxic to benthic invertebrates, and ammonia can also contribute to the toxicity of sediments that contain more persistent contaminants. We investigated the use of amendments of a natural zeolite mineral, clinoptilolite, to reduce concentrations of ammonia in sediment pore water. Zeolites have been widely used for removal of ammonia in water treatment and in aqueous TIE procedures. The addition of granulated zeolite to ammonia-spiked sediments reduced pore-water ammonia concentrations and reduced ammonia toxicity to invertebrates. Amendments of 20% zeolite (v/v) reduced ammonia concentrations in pore water by ???70% in spiked sediments with ammonia concentrations typical of contaminated freshwater sediments. Zeolite amendments reduced toxicity of ammonia-spiked sediments to three taxa of benthic invertebrates (Hyalella azteca, Lumbriculus variegatus, and Chironomus tentans), despite their widely differing sensitivity to ammonia toxicity. In contrast, zeolite amendments did not reduce acute toxicity of sediments containing high concentrations of cadmium or copper or reduce concentrations of these metals in pore waters. These studies suggest that zeolite amendments, used in conjunction with toxicity tests with sensitive taxa such as H. azteca, may be an effective technique for selective reduction of ammonia toxicity in freshwater sediments.

Phycoremediation of landfill leachate with the chlorophyte Chlamydomonas sp. SW15aRL and evaluation of toxicity pre and post treatment.

PubMed

Paskuliakova, Andrea; McGowan, Ted; Tonry, Steve; Touzet, Nicolas

2018-01-01

Landfill leachate treatment is an ongoing challenge in the wastewater management of existing sanitary landfill sites due to the complex nature of leachates and their heavy pollutant load. There is a continuous interest in treatment biotechnologies with expected added benefits for resource recovery; microalgal bioremediation is seen as promising in this regard. Toxicity reduction of landfill leachate subsequent to phycoremediation was investigated in this study. The treatment eventuated from the growth of the ammonia tolerant microalgal strain Chlamydomonas sp. SW15aRL using a N:P ratio adjustment in diluted leachate for facilitating the process. Toxicity tests ranging over a number of trophic levels were applied, including bacterial-yeast (MARA), protistean (microalgae growth inhibition test), crustacean (daphnia, rotifer) and higher plant (monocot, dicot) assays. Ammonia nitrogen in the diluted landfill leachate containing up to 158mgl -1 NH 4 + -N (60% dilution of the original) was reduced by 83% during the microalgal treatment. Testing prior to remediation indicated the highest toxicity in the crustacean assays Daphnia magna and Brachionus calyciflorus with EC50s at 24h of ~ 35% and 40% leachate dilution, respectively. A major reduction in toxicity was achieved with both bioassays post microalgal treatment with effects well below the EC20s. The microalgae inhibition test on the other hand indicated increased stimulation of growth after treatment as a result of toxicity reduction but also the presence of residual nutrients. Several concurrent processes of both biotic and abiotic natures contributed to pollutant reduction during the treatment. Modifying phosphate dosage especially seems to require further attention. As a by-product of the remediation process, up to 1.2gl -1 of microalgal biomass was obtained with ~ 18% DW lipid content. Copyright © 2017 Elsevier Inc. All rights reserved.

Priority screening of toxic chemicals and industry sectors in the U.S. toxics release inventory: a comparison of the life cycle impact-based and risk-based assessment tools developed by U.S. EPA.

PubMed

Lim, Seong-Rin; Lam, Carl W; Schoenung, Julie M

2011-09-01

Life Cycle Impact Assessment (LCIA) and Risk Assessment (RA) employ different approaches to evaluate toxic impact potential for their own general applications. LCIA is often used to evaluate toxicity potentials for corporate environmental management and RA is often used to evaluate a risk score for environmental policy in government. This study evaluates the cancer, non-cancer, and ecotoxicity potentials and risk scores of chemicals and industry sectors in the United States on the basis of the LCIA- and RA-based tools developed by U.S. EPA, and compares the priority screening of toxic chemicals and industry sectors identified with each method to examine whether the LCIA- and RA-based results lead to the same prioritization schemes. The Tool for the Reduction and Assessment of Chemical and other environmental Impacts (TRACI) is applied as an LCIA-based screening approach with a focus on air and water emissions, and the Risk-Screening Environmental Indicator (RSEI) is applied in equivalent fashion as an RA-based screening approach. The U.S. Toxic Release Inventory is used as the dataset for this analysis, because of its general applicability to a comprehensive list of chemical substances and industry sectors. Overall, the TRACI and RSEI results do not agree with each other in part due to the unavailability of characterization factors and toxic scores for select substances, but primarily because of their different evaluation approaches. Therefore, TRACI and RSEI should be used together both to support a more comprehensive and robust approach to screening of chemicals for environmental management and policy and to highlight substances that are found to be of concern from both perspectives. Copyright © 2011 Elsevier Ltd. All rights reserved.

Impact of water chemistry on the particle-specific toxicity of copper nanoparticles to Daphnia magna.

PubMed

Xiao, Yinlong; Peijnenburg, Willie J G M; Chen, Guangchao; Vijver, Martina G

2018-01-01

Toxicity of metallic nanoparticle suspensions (NP (total) ) is generally assumed to result from the combined effect of the particles present in suspensions (NP (particle) ) and their released ions (NP (ion) ). Evaluation and consideration of how water chemistry affects the particle-specific toxicity of NP (total) are critical for environmental risk assessment of nanoparticles. In this study, it was found that the toxicity of Cu NP (particle) to Daphnia magna, in line with the trends in toxicity for Cu NP (ion) , decreased with increasing pH and with increasing concentrations of divalent cations and dissolved organic carbon (DOC). Without the addition of DOC, the toxicity of Cu NP (total) to D. magna at the LC50 was driven mainly by Cu NP (ion) (accounting for ≥53% of the observed toxicity). However, toxicity of Cu NP (total) in the presence of DOC at a concentration ranging from 5 to 50mg C/L largely resulted from the NP (particle) (57%-85%), which could be attributable to the large reduction of the concentration of Cu NP (ion) and the enhancement of the stability of Cu NP (particle) when DOC was added. Our results indicate that water chemistry needs to be explicitly taken into consideration when evaluating the role of NP (particle) and NP (ion) in the observed toxicity of NP (total) . Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the Treatment Process of Landfill Leachate Using the Toxicity Assessment Method

PubMed Central

Qiu, Aifeng; Cai, Qiang; Zhao, Yuan; Guo, Yingqing; Zhao, Liqian

2016-01-01

Landfill leachate is composed of a complex composition with strong biological toxicity. The combined treatment process of coagulation and sedimentation, anaerobics, electrolysis, and aerobics was set up to treat landfill leachate. This paper explores the effect of different operational parameters of coagulation and sedimentation tanks and electrolytic cells, while investigating the combined process for the removal efficiency of physicochemical indices after processing the landfill leachate. Meanwhile, a battery of toxicity tests with Vibrio fischeri, zebrafish larvae, and embryos were conducted to evaluate acute toxicity and calculated the toxicity reduction efficiency after each treatment process. The combined treatment process resulted in a 100% removal efficiency of Cu, Cd and Zn, and a 93.50% and an 87.44% removal efficiency of Ni and Cr, respectively. The overall removal efficiency of chemical oxygen demand (COD), ammonium nitrogen (NH4+-N), and total nitrogen (TN) were 93.57%, 97.46% and 73.60%, respectively. In addition, toxicity test results showed that the acute toxicity of landfill leachate had also been reduced significantly: toxicity units (TU) decreased from 84.75 to 12.00 for zebrafish larvae, from 82.64 to 10.55 for zebrafish embryos, and from 3.41 to 0.63 for Vibrio fischeri. The combined treatment process was proved to be an efficient treatment method to remove heavy metals, COD, NH4+-N, and acute bio-toxicity of landfill leachate. PMID:28009808

Evaluation of the Treatment Process of Landfill Leachate Using the Toxicity Assessment Method.

PubMed

Qiu, Aifeng; Cai, Qiang; Zhao, Yuan; Guo, Yingqing; Zhao, Liqian

2016-12-21

Landfill leachate is composed of a complex composition with strong biological toxicity. The combined treatment process of coagulation and sedimentation, anaerobics, electrolysis, and aerobics was set up to treat landfill leachate. This paper explores the effect of different operational parameters of coagulation and sedimentation tanks and electrolytic cells, while investigating the combined process for the removal efficiency of physicochemical indices after processing the landfill leachate. Meanwhile, a battery of toxicity tests with Vibrio fischeri , zebrafish larvae, and embryos were conducted to evaluate acute toxicity and calculated the toxicity reduction efficiency after each treatment process. The combined treatment process resulted in a 100% removal efficiency of Cu, Cd and Zn, and a 93.50% and an 87.44% removal efficiency of Ni and Cr, respectively. The overall removal efficiency of chemical oxygen demand (COD), ammonium nitrogen (NH₄⁺-N), and total nitrogen (TN) were 93.57%, 97.46% and 73.60%, respectively. In addition, toxicity test results showed that the acute toxicity of landfill leachate had also been reduced significantly: toxicity units (TU) decreased from 84.75 to 12.00 for zebrafish larvae, from 82.64 to 10.55 for zebrafish embryos, and from 3.41 to 0.63 for Vibrio fischeri . The combined treatment process was proved to be an efficient treatment method to remove heavy metals, COD, NH₄⁺-N, and acute bio-toxicity of landfill leachate.

Reduction on the anaerobic biological activity inhibition caused by heavy metals and sulphates in effluents through chemical precipitation with soda and lime.

PubMed

Alves, L de Carvalho; Cammarota, M C; De França, F P

2006-12-01

The School of Chemistry Environmental Technology Laboratory generates 43.4 1 of effluent with low pH (0.7) and high contents of COD (1908 mgO2 l(-1)), phenol (132.1 mg l(-1)), sulfate (36700 mg l(-1)) and heavy metals (28.2 mg Hg l(-1); 82.1 mg Cr(total) l(-1); 30.8 mg Cu l(-1); 57.4 mg Fe(total) l(-1); 16.2 mg Al l(-1)) weekly. These data show that this effluent presents high toxicity for biological treatment, with a physical-chemical step being necessary before a biological step. Preliminary studies showed that the most toxic constituents of the effluent were sulfate, phenol and total chromium. In this work, a chemical precipitation step with sodium hydroxide or lime was evaluated for the toxicity reduction on anaerobic microbial consortium. These experiments were carried out with increasing concentrations of alkalis in the effluent in order to obtain pH initial values of 8-12. Similar results were obtained for COD (15-28%), turbidity (95-98%), phenol (13-24%) and total chromium (99.8-99.9%) removals in each condition studied with soda or lime. Sulfate was only removed by precipitation with lime, obtaining reductions from 84 to 88%. The toxicity on the anaerobic sludge was studied employing specific methanogenic activity (SMA) analysis of raw and treated effluent (after chemical precipitation step). The SMA experiments showed that chemical precipitation at pH 8 reduces the toxic effect of the effluent on anaerobic microbial consortium three times (with soda) and thirteen times (with lime). These results indicate that precipitation with lime is more efficient at toxicity removal, however the produced sludge volume is around two times higher than that produced with soda.

DEGRADATION OF POLYNUCLEAR AROMATIC HYDROCARBONS UNDER BENCH-SCALE COMPOST CONDITIONS

EPA Science Inventory

The relationship between biomass growth and degradation of polynuclear aromatic hydrocarbons (PAHs) in soil, and subsequent toxicity reduction, was evaluated in 10 in-vessel, bench-scale compost units. Field soil was aquired from the Reilly Tar and Chemical Company Superfund site...

Toxicity, tunneling and feeding behavior of the termite, Coptotermes vastator, in sand treated with oil of the physic nut, Jatropha curcas.

PubMed

Acda, Menandro N

2009-01-01

Oil of the physic nut, Jatropha curcas L. (Malpighiales: Euphorbiaceae), was evaluated in the laboratory for its barrier and repellent activity against the Philippine milk termite Coptotermes vastator Light (Isoptera: Rhinotermitidae). The study showed that J. curcas oil had anti-feeding effect, induced reduction in tunneling activity and increased mortality in C. vastator. Behavior of termites exposed to sand treated with J. curcas oil indicated that it is toxic or repellent to C. vastator. Toxicity and repellent thresholds, were higher than those reported for other naturally occurring compounds tested against the Formosan subterranean termite.

Toxicity, Tunneling and Feeding Behavior of the Termite, Coptotermes vastator, in Sand Treated with Oil of the Physic Nut, Jatropha curcas

PubMed Central

Acda, Menandro N.

2009-01-01

Oil of the physic nut, Jatropha curcas L. (Malpighiales: Euphorbiaceae), was evaluated in the laboratory for its barrier and repellent activity against the Philippine milk termite Coptotermes vastator Light (Isoptera: Rhinotermitidae). The study showed that J. curcas oil had anti-feeding effect, induced reduction in tunneling activity and increased mortality in C. vastator. Behavior of termites exposed to sand treated with J. curcas oil indicated that it is toxic or repellent to C. vastator. Toxicity and repellent thresholds, were higher than those reported for other naturally occurring compounds tested against the Formosan subterranean termite. PMID:20053119

Toxicity of textile dyes and their degradation by the enzyme horseradish peroxidase (HRP).

PubMed

Ulson de Souza, Selene Maria Arruda Guelli; Forgiarini, Eliane; Ulson de Souza, Antônio Augusto

2007-08-25

The enzyme peroxidase is known for its capacity to remove phenolic compounds and aromatic amines from aqueous solutions and also to decolorize textile effluents. This study evaluates the potential of the enzyme horseradish peroxidase (HRP) in the decolorization of textile dyes and effluents. Some factors such as pH and the amount of H(2)O(2) and the enzyme were evaluated in order to determine the optimum conditions for the enzyme performance. For the dyes tested, the results indicated that the decolorization of the dye Remazol Turquoise Blue G 133% was approximately 59%, and 94% for the Lanaset Blue 2R; for the textile effluent, the decolorization was 52%. The tests for toxicity towards Daphnia magna showed that there was a reduction in toxicity after the enzymatic treatment. However, the toxicity of the textile effluent showed no change towards Artemia salina after the enzyme treatment. This study verifies the viability of the use of the enzyme horseradish peroxidase in the biodegradation of textile dyes.

Sulfate Assimilation Mediates Tellurite Reduction and Toxicity in Saccharomyces cerevisiae▿†

PubMed Central

Ottosson, Lars-Göran; Logg, Katarina; Ibstedt, Sebastian; Sunnerhagen, Per; Käll, Mikael; Blomberg, Anders; Warringer, Jonas

2010-01-01

Despite a century of research and increasing environmental and human health concerns, the mechanistic basis of the toxicity of derivatives of the metalloid tellurium, Te, in particular the oxyanion tellurite, Te(IV), remains unsolved. Here, we provide an unbiased view of the mechanisms of tellurium metabolism in the yeast Saccharomyces cerevisiae by measuring deviations in Te-related traits of a complete collection of gene knockout mutants. Reduction of Te(IV) and intracellular accumulation as metallic tellurium strongly correlated with loss of cellular fitness, suggesting that Te(IV) reduction and toxicity are causally linked. The sulfate assimilation pathway upstream of Met17, in particular, the sulfite reductase and its cofactor siroheme, was shown to be central to tellurite toxicity and its reduction to elemental tellurium. Gene knockout mutants with altered Te(IV) tolerance also showed a similar deviation in tolerance to both selenite and, interestingly, selenomethionine, suggesting that the toxicity of these agents stems from a common mechanism. We also show that Te(IV) reduction and toxicity in yeast is partially mediated via a mitochondrial respiratory mechanism that does not encompass the generation of substantial oxidative stress. The results reported here represent a robust base from which to attack the mechanistic details of Te(IV) toxicity and reduction in a eukaryotic organism. PMID:20675578

Aluminium Toxicity to Plants as Influenced by the Properties of the Root Growth Environment Affected by Other Co-Stressors: A Review.

PubMed

Siecińska, Joanna; Nosalewicz, Artur

Aluminium toxicity to crops depends on the acidity of the soil and specific plant resistance. However, it is also strongly affected by other environmental factors that have to be considered to properly evaluate the resultant effects on plants. Observed weather perturbations and predicted climate changes will increase the probability of co-occurrence of aluminium toxicity and other abiotic stresses.In this review the mechanisms of plant-aluminium interactions are shown to be influenced by soil mineral nutrients, heavy metals, organic matter, oxidative stress and drought. Described effects of aluminium toxicity include: root growth inhibition, reduction in the uptake of mineral nutrients resulting from the inhibition of transport processes through ion channels; epigenetic changes to DNA resulting in gene silencing. Complex processes occurring in the rhizosphere are highlighted, including the role of soil organic matter and aluminium detoxification by mucilage.There is a considerable research gap in the understanding of root growth in the soil environment in the presence of toxic aluminium concentrations as affected by interactions with abiotic stressors. This knowledge is important for the selection of feasible methods aimed at the reduction of negative consequences of crop production in acidic soils affected by adverse growth environment.

Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction.

PubMed

Pujol-Vila, F; Vigués, N; Guerrero-Navarro, A; Jiménez, S; Gómez, D; Fernández, M; Bori, J; Vallès, B; Riva, M C; Muñoz-Berbel, X; Mas, J

2016-03-03

Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox(®), rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation requirements and the simplicity of the bioassay open the possibility of in-situ water toxicity assessment with a fast and low-cost protocol. Copyright © 2016 Elsevier B.V. All rights reserved.

Miniaturized blood sampling techniques to benefit reduction in mice and refinement in nonhuman primates: applications to bioanalysis in toxicity studies with antibody-drug conjugates.

PubMed

Caron, Alexis; Lelong, Christine; Pascual, Marie-Hélène; Benning, Véronique

2015-03-01

Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development of miniaturized blood sampling methods (including microsampling and dried blood spots) applicable to toxicokinetic determinations of small-molecule drugs. Implementation of miniaturized blood sampling methods in the context of biotherapeutic drugs is desirable because a limitation to this type of medicine remains the total blood volume needed from a single animal to support toxicokinetic determinations of several analytes (parent drug, metabolites[s], antidrug antibodies, and so forth). We describe here the technical details, applicability, and relevance of new miniaturized blood sampling procedures in mice and nonhuman primates in the context of the toxicologic evaluation of biotherapeutic drugs consisting of antibody-drug conjugates developed for oncology indications. These examples illustrate how these techniques can benefit the reduction of animal usage in mouse toxicity studies by decreasing the number of animals dedicated to toxicokinetic determinations and the refinement of practices in nonhuman primate toxicity studies by decreasing the blood volume repeatedly drawn for toxicokinetic determinations.

Miniaturized Blood Sampling Techniques to Benefit Reduction in Mice and Refinement in Nonhuman Primates: Applications to Bioanalysis in Toxicity Studies with Antibody–Drug Conjugates

PubMed Central

Caron, Alexis; Lelong, Christine; Pascual, Marie-Hélène; Benning, Véronique

2015-01-01

Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development of miniaturized blood sampling methods (including microsampling and dried blood spots) applicable to toxicokinetic determinations of small-molecule drugs. Implementation of miniaturized blood sampling methods in the context of biotherapeutic drugs is desirable because a limitation to this type of medicine remains the total blood volume needed from a single animal to support toxicokinetic determinations of several analytes (parent drug, metabolites[s], antidrug antibodies, and so forth). We describe here the technical details, applicability, and relevance of new miniaturized blood sampling procedures in mice and nonhuman primates in the context of the toxicologic evaluation of biotherapeutic drugs consisting of antibody–drug conjugates developed for oncology indications. These examples illustrate how these techniques can benefit the reduction of animal usage in mouse toxicity studies by decreasing the number of animals dedicated to toxicokinetic determinations and the refinement of practices in nonhuman primate toxicity studies by decreasing the blood volume repeatedly drawn for toxicokinetic determinations. PMID:25836960

Somatostatin analogs and disease control in castration-resistant prostate cancer: different biological behavior? Case series and review of the literature.

PubMed

D'Angelillo, Rolando Maria; Greco, Carlo; Fiore, Michele; Ippolito, Edy; Eolo Trodella, Luca; Iurato, Aurelia; Molfese, Elisabetta; Ramella, Sara; Trodella, Lucio

2014-01-01

Castration-resistant prostate cancer is a recent biological behavior where disease can elude androgen deprivation therapy (ADT). Several pathways have been described, including neuroendocrine dedifferentiation. Patients with neuroendocrine dedifferentiation show an increase in chromogranin A (CgA) along with a PSA increase. Our aim was to evaluate the response of patients with castration-resistant prostate cancer and high CgA serum levels after treatment with inhibitors of neuroendocrine cells (somatostatin analogs) in combination with ADT. From January 2009 to April 2011, 10 patients with castration-resistant prostate cancer and rising PSA levels along with a CgA increase were evaluated. The therapy was based on somatostatin analogs and LHRH anologs. Total PSA and CgA were measured every 2 months. In 9 of the 10 patients, a reduction of the values of pre-treatment CgA was detected, while a reduction of PSA was found in 8 patients. No grade 2 or higher toxicity was recorded. Only 3 patients had grade 1 gastrointestinal toxicity. Time to progression was 13 months. Therapy with somatostatin analogs could increase the therapeutic window of ADT with a low toxicity profile in a subpopulation of patients with castration-resistant prostate cancer who experience a rise in CgA due to neuroendocrine regulation.

TOXICITY REDUCTION EVALUATION (TRE) AT A MUNICIPAL WASTEWATER TREATMENT PLANT USING MUTAGENICITY AS AN END- POINT

EPA Science Inventory

Previous work revealed substantial levels of mutagenicity in effluents from certain municipal wastewater treatment plants. One of these treatment plants was selected for further study to track the effluent mutagenicity to its sources, to chemically characterize the mutagenicity, ...

Development of a toxicity identification evaluation procedure for characterizing metal toxicity in marine sediments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burgess, R.M.; Cantwell, M.G.; Pelletier, M.C.

2000-04-01

A multiagency effort is underway to develop whole sediment toxicity identification evaluation (TIE) methods. Whole sediment TIE methods will be critical tools for characterizing toxicity at hazardous waste sites and in the conduct of environmental risk assessments. The research approach is based on the predominance of three classes of toxicants in sediments: ammonia, nonpolar organic chemicals, and metals. Here the authors describe a procedure for characterizing acute toxicity caused by metals in whole marine sediments. The procedure involves adding a chelating resin to sediments, resulting in the sequestration of bioavailable metal while not stressing testing organisms. Within the testing chambers,more » the presence of resin resulted in statistically significant reductions in the overlying and interstitial water concentrations of five metals (cadmium, copper, nickel, lead, and zinc) generally by factors of 40 and 200. Toxicity to both the amphipod Ampelisca abdita and mysid Americamysis bahia (formerly Mysidopsis bahia) of sediments spiked with the five metals was decreased by approximately a factor of four when resin was present. While very effective at reducing the concentrations and toxicity of metals, the resin has only minor ameliorative effects on the toxicity of ammonia and a representative nonpolar toxicant (Endosulfan). Resin and accumulated metal were easily isolated from the testing system following exposures allowing for the initiation of phase II TIE (identification) procedures. This procedure using the addition of a chelating resin provides an approach for determining the importance of metals to the toxicity of marine sediments. Work is continuing to validate the method with environmentally contaminated sediments.« less

Guidance on the selection of cohorts for the extended one-generation reproduction toxicity study (OECD test guideline 443).

PubMed

Moore, Nigel P; Beekhuijzen, Manon; Boogaard, Peter J; Foreman, Jennifer E; North, Colin M; Palermo, Christine; Schneider, Steffen; Strauss, Volker; van Ravenzwaay, Bennard; Poole, Alan

2016-10-01

The extended one-generation reproduction toxicity study (EOGRTS; OECD test guideline 433) is a new and technically complex design to evaluate the putative effects of chemicals on fertility and development, including effects upon the developing nervous and immune systems. In addition to offering a more comprehensive assessment of developmental toxicity, the EOGRTS offers important improvements in animal welfare through reduction and refinement in a modular study design. The challenge to the practitioner is to know how the modular aspects of the study should be triggered on the basis of prior knowledge of a particular chemical, or on earlier findings in the EOGRTS itself, requirements of specific regulatory frameworks notwithstanding. The purpose of this document is to offer guidance on science-based triggers for these extended evaluations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Influence of Study Design on Developmental and Reproductive Toxicology Study Outcomes.

PubMed

Foster, Paul M D

2017-01-01

Regulatory studies of developmental and reproductive toxicity (DART) studies have remained largely unchanged for decades, with exposures occurring at various phases of the reproductive cycle and toxicity evaluations at different ages/times depending on the study purpose. The National Toxicology Program has conducted studies examining the power to detect adverse effects where there is a prenatal exposure, but evaluations occur postnatally. In these studies, examination is required of only 1 male and female pup from each litter beyond weaning. This provides poor resolving power to detect rare events (e.g., reproductive tract malformations). If an adverse effect is detected, there is little confidence in the shape of the dose-response curve (and the Benchmark Dose or No Observed Adverse Effect Level [NOAEL]). We have developed a new protocol to evaluate DART, the modified one generation study, with exposure commencing with pregnant animals and retention of 4 males and females from each litter beyond weaning to improve statistical power. These animals can be allocated to specific cohorts that examine subchronic toxicity, teratology, littering, and neurobehavioral toxicity in the same study. This approach also results in a reduction in animal numbers used, compared with individual stand-alone studies, and offers increased numbers of end points evaluated compared with recent Organization for Economic Cooperation and Development proposals.

Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract of Dicoma anomala Sond. in Wistar Rats

PubMed Central

Balogun, Fatai Oladunni; Tom Ashafa, Anofi Omotayo

2016-01-01

The present study evaluated the safety of aqueous root extract of Dicoma anomala (AQRED) through acute and subchronic toxicity studies. Single oral dose of AQRED at the concentration of 0, 5, 300, and 2000 mg/kg as well as 125, 250, and 500 mg/kg/day was administered to rats for 14-day acute and 90-day subchronic oral toxicity studies. The results revealed no mortalities or observed clinical signs of toxicity in all the rats during both investigation periods. In subchronic toxicity testing, administration of AQRED also did not cause any changes in body weight as well as food and water consumption patterns. The haematological parameters and blood chemistry revealed no significant difference (p > 0.05) between the treatment and the control except in platelet count, alkaline phosphatase, and sodium levels where there was a significant increase (p < 0.05), although there was also a significant reduction (p < 0.05) in alanine transaminase, aspartate transaminase, and creatinine when compared to control. However, these changes were not reflecting the results from histology. Conclusively, the obtained results suggested that the LD50 of AQRED is in excess of 2000 mg/kg and its oral administration for 90 days revealed that it is unlikely to be toxic, hence, safe. PMID:27200099

CO-DEPENDENCIES OF REACTIVE AIR TOXIC AND CRITERIA POLLUTANTS ON EMISSION REDUCTIONS

EPA Science Inventory

It is important to understand the effect of emission controls on the concentrations of ozone, PM_2.5, and hazardous air pollutants simultaneously, in order to evaluate the full range of both health related and economic effects. Until recently, the capability of simultan...

In vitro toxicities of experimental jet fuel system ice-inhibiting agents.

PubMed

Geiss, K T; Frazier, J M

2001-07-02

One research emphasis within the Department of Defense has been to seek the replacement of operational compounds with alternatives that pose less potential risk to human and ecological systems. Alternatives to glycol ethers, such as diethylene glycol monomethyl ether (M-DE), were investigated for use as jet fuel system ice-inhibiting agents (FSIIs). This group of chemicals includes three derivatives of 1,3-dioxolane-4-methanol (M-1, M-2, and M-3) and a 1,3-dioxane (M-27). In addition, M-DE was evaluated as a reference compound. Our approach was to implement an in vitro test battery based on primary rat hepatocyte cultures to perform initial toxicity evaluations. Hepatocytes were exposed to experimental chemicals (0, 0.001, 0.01, 0.1, 1, 10 mM dosages) for periods up to 24 h. Samples were assayed for lactate dehydrogenase (LDH) release, MTT dye reduction activity, glutathione level, and rate of protein synthesis as indicators of toxicity. Of the compounds tested, M-1, especially at the 10-mM dose, appeared to be more potent than the other chemicals, as measured by these toxicity assays. M-DE, the current FSII, elicited little response in the toxicity assays. Although some variations in toxicity were observed at the 10-mM dose, the in vitro toxicities of the chemicals tested (except for M-1) were not considerably greater than that of M-DE.

Addition of biochar to sewage sludge decreases freely dissolved PAHs content and toxicity of sewage sludge-amended soil.

PubMed

Stefaniuk, Magdalena; Oleszczuk, Patryk

2016-11-01

Due to an increased content of polycyclic aromatic hydrocarbons (PAHs) frequently found in sewage sludges, it is necessary to find solutions that will reduce the environmental hazard associated with their presence. The aim of this study was to determine changes of total and freely dissolved concentration of PAHs in sewage sludge-biochar-amended soil. Two different sewage sludges and biochars with varying properties were tested. Biochars (BC) were produced from biogas residues at 400 °C or 600 °C and from willow at 600 °C. The freely dissolved PAH concentration was determined by means of passive sampling using polyoxymethylene (POM). Total and freely dissolved PAH concentration was monitored at the beginning of the experiment and after 90 days of aging of the sewage sludge with the biochar and soil. Apart from chemical evaluation, the effect of biochar addition on the toxicity of the tested materials on bacteria - Vibrio fischeri (Microtox ® ), plants - Lepidium sativum (Phytotestkit F, Phytotoxkit F), and Collembola - Folsomia candida (Collembolan test) was evaluated. The addition of biochar to the sewage sludges decreased the content of C free PAHs. A reduction from 11 to 43% of sewage sludge toxicity or positive effects on plants expressed by root growth stimulation from 6 to 25% to the control was also found. The range of reduction of C free PAHs and toxicity was dependent on the type of biochar. After 90 days of incubation of the biochars with the sewage sludge in the soil, C free PAHs and toxicity were found to further decrease compared to the soil with sewage sludge alone. The obtained results show that the addition of biochar to sewage sludges may significantly reduce the risk associated with their environmental use both in terms of PAH content and toxicity of the materials tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microbial stabilization and mass reduction of wastes containing radionuclides and toxic metals

DOEpatents

Francis, A.J.; Dodge, C.J.; Gillow, J.B.

1991-09-10

A process is provided to treat wastes containing radionuclides and toxic metals with Clostridium sp. BFGl to release a large fraction of the waste solids into solution and convert the radionuclides and toxic metals to a more concentrated and stable form with concurrent volume and mass reduction. The radionuclides and toxic metals being in a more stable form are available for recovery, recycling and disposal. 18 figures.

Microbial stabilization and mass reduction of wastes containing radionuclides and toxic metals

DOEpatents

Francis, Arokiasamy J.; Dodge, Cleveland J.; Gillow, Jeffrey B.

1991-01-01

A process is provided to treat wastes containing radionuclides and toxic metals with Clostridium sp. BFGl to release a large fraction of the waste solids into solutin and convert the radionuclides and toxic metals to a more concentrated and stable form with concurrent volume and mass reduction. The radionuclides and toxic metals being in a more stable form are available for recovery, recycling and disposal.

Toxics Use Reduction in the Home: Lessons Learned from Household Exposure Studies

PubMed Central

Dunagan, Sarah C.; Dodson, Robin E.; Rudel, Ruthann A.; Brody, Julia G.

2010-01-01

Workers and fence-line communities have been the first to benefit from the substantial reductions in toxic chemical use and byproducts in industrial production resulting from the Massachusetts Toxics Use Reduction Act (TURA). As TURA motivates reformulation of products as well as retooling of production processes, benefits could extend more broadly to large-scale reductions in everyday exposures for the general population. Household exposure studies, including those conducted by Silent Spring Institute, show that people are exposed to complex mixtures of indoor toxics from building materials and a myriad of consumer products. Pollutants in homes are likely to have multiple health effects because many are classified as endocrine disrupting compounds (EDCs), with the ability to interfere with the body's hormone system. Product-related EDCs measured in homes include phthalates, halogenated flame retardants, and alkylphenols. Silent Spring Institute's chemical analysis of personal care and cleaning products confirms many are potential sources of EDCs, highlighting the need for a more comprehensive toxics use reduction (TUR) approach to reduce those exposures. Toxics use reduction targeted at EDCs in consumer products has the potential to substantially reduce occupational and residential exposures. The lessons that have emerged from household exposure research can inform improved chemicals management policies at the state and national levels, leading to safer products and widespread health and environmental benefits. PMID:21516227

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

PubMed

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.

Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.

PubMed

Postel-Vinay, Sophie; Collette, Laurence; Paoletti, Xavier; Rizzo, Elisa; Massard, Christophe; Olmos, David; Fowst, Camilla; Levy, Bernard; Mancini, Pierre; Lacombe, Denis; Ivy, Percy; Seymour, Lesley; Le Tourneau, Christophe; Siu, Lillian L; Kaye, Stan B; Verweij, Jaap; Soria, Jean-Charles

2014-08-01

Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients. Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. Copyright © 2014 Elsevier Ltd. All rights reserved.

An Eco-Safety Assessment of Glyoxal-Containing Cellulose Ether on Freeze-Dried Microbial Strain, Cyanobacteria, Daphnia, and Zebrafish

PubMed Central

Park, Chang-Beom; Song, Min Ju; Choi, Nak Woon; Kim, Sunghoon; Jeon, Hyun Pyo; Kim, Sanghun; Kim, Youngjun

2017-01-01

The objective of this study was to investigate the aquatic-toxic effects of glyoxal-containing cellulose ether with four different glyoxal concentrations (0%, 1.4%, 2.3%, and 6.3%) in response to global chemical regulations, e.g., European Union Classification, Labeling and Packaging (EU CLP). Toxicity tests of glyoxal-containing cellulose ether on 11 different microbial strains, Microcystis aeruginosa, Daphnia magna, and zebrafish embryos were designed as an initial stage of toxicity screening and performed in accordance with standardized toxicity test guidelines. Glyoxal-containing cellulose ether showed no significant toxic effects in the toxicity tests of the 11 freeze-dried microbial strains, Daphnia magna, and zebrafish embryos. Alternatively, 6.3% glyoxal-containing cellulose ether led to a more than 60% reduction in Microcystis aeruginosa growth after 7 days of exposure. Approximately 10% of the developmental abnormalities (e.g., bent spine) in zebrafish embryos were also observed in the group exposed to 6.3% glyoxal-containing cellulose ether after 6 days of exposure. These results show that 6.3% less glyoxal-containing cellulose ether has no acute toxic effects on aquatic organisms. However, 6.3% less glyoxal-containing cellulose ether may affect the health of aquatic organisms with long-term exposure. In order to better evaluate the eco-safety of cellulosic products containing glyoxal, further studies regarding the toxic effects of glyoxal-containing cellulose ether with long-term exposure are required. The results from this study allow us to evaluate the aquatic-toxic effects of glyoxal-containing cellulosic products, under EU chemical regulations, on the health of aquatic organisms. PMID:28335565

Evaluation of genomic biomarkers and relative potency of phthalate-induced male reproductive developmental toxicity using a targeted rtPCR array approach**

EPA Science Inventory

Exposure to certain phthalate esters (PEs) during sexual differentiation induces reproductive tract malformations in male rats due to reductions in fetal testicular testosterone (T) production and expression of steroidogenesis-and insl3-related genes. In the current study, we use...

Degradation of parathion and the reduction of acute toxicity in TiO2 photocatalysis.

PubMed

Zoh, K D; Kim, T S; Kim, J G; Choi, K H

2005-01-01

Photocatalytic degradation of methyl parathion was done using a circulating TiO2/UV and TiO2/solar reactor. Indoor experimental results showed that, under the photocatalysis conditions, parathion was more effectively degraded than under the photolysis and TiO2 only conditions. Parathion (38 microM) was completely degraded under photocatalysis within 90 min, and more than 80% TOC decrease after 150 minutes. The main ionic byproducts during the photocatalysis were measured, and almost complete nitrogen recovery was achieved as mainly NO3- NO2-, and NH4+, and 80% of sulfur as recovered as SO4(2)-. Organic intermediates such as nitrophenol and methyl paraoxon were also identified during the photocatalysis of parathion, and these were further degraded after 90 minutes. Microtox bioassay using Vibrio fischeri was used in evaluating the toxicity of solutions treated by photocatalysis and photolysis of parathion. The results showed that the acute toxicity expressed as EC50 almost reduced after 90 min under the photocatalysis condition whereas only 40% reduction of toxicity as EC50 was achieved in photolysis condition. The outdoor results using a TiO2/solar system were similar to the TiO2 indoor system, indicating the possibility of applying TiO2/solar system for the treatment of parathion-contaminated water.

Mycological and ecotoxicological characterisation of landfill leachate before and after traditional treatments.

PubMed

Tigini, Valeria; Prigione, Valeria; Varese, Giovanna Cristina

2014-07-15

Pollution caused by landfill leachates is one of the main problems of urbanised areas, on account of their chemical composition, which turn in an ineffective treatment. A characterisation of leachates, which takes into account chemical, ecotoxicological and mycological aspects, is basilar for the evaluation of environmental impact of leachate and the development of suitable treatment techniques. In this study, the toxicity of a raw leachate and an effluent coming from traditional wastewater treatment plant was assessed by means of 4 ecotoxicological assays. Both the samples exceed the legal threshold value according to all the tested organisms, indicating the ineffectiveness of activated sludge treatment in the reduction of toxicity. The autochthonous mycoflora of the two samples was evaluated by filtration. The fungal load was 73 CFU for leachate and 102 CFU for the effluent. Ascomycetes were the dominant fraction (81% and 61%, for leachate and effluent respectively), followed by basidiomycetes (19% and 39%, respectively). Most of them were potential emerging pathogens. A decolourisation screening with autochthonous fungi was set up towards both samples in the presence or absence of glucose. Eleven fungi (basidiomycetes and ascomycetes) achieved up to 38% decolourisation yields, showing to be promising fungi for the bioremediation of leachates. Further experiment will be aimed to the study of decolourisation mechanism and toxicity reduction. Copyright © 2014 Elsevier B.V. All rights reserved.

Moderate hypofractionated radiotherapy with volumetric modulated arc therapy and simultaneous integrated boost for pelvic irradiation in prostate cancer.

PubMed

Franzese, C; Fogliata, A; D'Agostino, G R; Di Brina, L; Comito, T; Navarria, P; Cozzi, L; Scorsetti, M

2017-07-01

The optimal treatment for unfavourable intermediate/high-risk prostate cancer is still debated. In the present study, the pattern of toxicity and early clinical outcome of patients with localized prostate cancer was analyzed. A cohort of 90 patients treated on pelvic lymph nodes from 2010 to 2015 was selected. All patients were treated with Volumetric Modulated Arc Therapy (VMAT), and Simultaneous integrated boost (SIB) in 28 fractions; the prostate, the seminal vesicle and the pelvic lymph node received total doses of 74.2, 65.5, and 51.8 Gy, respectively. End points were the detection of acute and late toxicities graded according to the Common Toxicity Criteria CTCAE version 3, evaluating the rectal, genito-urinary and gastro-intestinal toxicity. Correlation of OARs dose parameters and related toxicities was explored. Preliminary overall survival and Progression-free survival (PFS) were evaluated. With a median follow-up of 25 months, no interruptions for treatment-related toxicity were recorded. Univariate analysis among dosimetric data and acute toxicities showed no correlations. Regarding late toxicity: the dose received by a rectal volume of 90 cm 3 was found to be significant for toxicity prediction (p = 0.024). PFS was 90.6% and 60.2% at 2 and 4 years, respectively. PFS correlates with age (p = 0.011) and Gleason score (p = 0.011). Stratifying the PSA nadir in quartiles, its value was significant (p = 0.016) in predicting PFS, showing a reduction of PFS of 2 months for each PSA-nadir increase of 0.1 ng/ml. HRT with VMAT and SIB on the whole pelvis in unfavourable prostate cancer patients is effective with a mild pattern of toxicity.

Evaluation of zinc oxide nanoparticles toxicity on marine algae chlorella vulgaris through flow cytometric, cytotoxicity and oxidative stress analysis.

PubMed

Suman, T Y; Radhika Rajasree, S R; Kirubagaran, R

2015-03-01

The increasing industrial use of nanomaterials during the last decades poses a potential threat to the environment and in particular to organisms living in the aquatic environment. In the present study, the toxicity of zinc oxide nanoparticles (ZnO NPs) was investigated in Marine algae Chlorella vulgaris (C. vulgaris). High zinc dissociation from ZnONPs, releasing ionic zinc in seawater, is a potential route for zinc assimilation and ZnONPs toxicity. To examine the mechanism of toxicity, C. vulgaris were treated with 50mg/L, 100mg/L, 200mg/L and 300 mg/L ZnO NPs for 24h and 72h. The detailed cytotoxicity assay showed a substantial reduction in the viability dependent on dose and exposure. Further, flow cytometry revealed the significant reduction in C. vulgaris viable cells to higher ZnO NPs. Significant reductions in LDH level were noted for ZnO NPs at 300 mg/L concentration. The activity of antioxidant enzyme superoxide dismutase (SOD) significantly increased in the C. vulgaris exposed to 200mg/L and 300 mg/L ZnO NPs. The content of non-enzymatic antioxidant glutathione (GSH) significantly decreased in the groups with a ZnO NPs concentration of higher than 100mg/L. The level of lipid peroxidation (LPO) was found to increase as the ZnO NPs dose increased. The FT-IR analyses suggested surface chemical interaction between nanoparticles and algal cells. The substantial morphological changes and cell wall damage were confirmed through microscopic analyses (FESEM and CM). Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of steam activation of biochar produced from a giant Miscanthus on copper sorption and toxicity.

PubMed

Shim, Taeyong; Yoo, Jisu; Ryu, Changkook; Park, Yong-Kwon; Jung, Jinho

2015-12-01

This study aims to evaluate the physiochemical properties, sorption characteristics, and toxicity effects of biochar (BC) produced from Miscanthus sacchariflorus via slow pyrolysis at 500°C and its steam activation product (ABC). Although BC has a much lower surface area than ABC (181 and 322m(2)g(-1), respectively), the Cu sorption capacities of BC and ABC are not significantly different (p>0.05). A two-compartment model successfully explains the sorption of BC and ABC as being dominated by fast and slow sorption processes, respectively. In addition, both BC and ABC efficiently eliminate the toxicity of Cu towards Daphnia magna. However, ABC itself induced acute toxicity to D. magna, which is possibly due to increased aromaticity upon steam activation. These findings suggest that activation of BC produced from M. sacchariflorus at a pyrolytic temperature of 500°C may not be appropriate in terms of Cu sorption and toxicity reduction. Copyright © 2015 Elsevier Ltd. All rights reserved.

A systems evaluation on the effectiveness of a catalyst retrofit program in China.

PubMed

Jones, M; Wilson, R; Norbeck, J M; Han, W; Hurley, R; Schuetzle, D

2001-09-01

A low-cost, rare-earth oxide (REO) catalyst has been recommended as part of China's retrofit program for Chinese carbureted vehicles. This study evaluated: (1) the emission reduction efficiency of the REO catalyst during chassis dynamometer testing on the FTP cycle; (2) the effect that fuel properties had on tailpipe emissions and catalyst efficiency; (3) the importance of vehicle premaintenance as part of a retrofit protocol; and (4) the emission reductions obtained following implementation of the program. Results also show that current in-use Chinese noncatalyst, carbureted vehicles operate excessively rich, resulting in extremely high emissions of CO, gaseous toxic compounds, and other non-methane hydrocarbon species (NMHC). Preretrofit maintenance alone has the potential to reduce these emissions by approximately 50%. Dynamometer emission tests showed emissions reductions of >95% for hydrocarbons, CO, and gaseous toxics after retrofit of the REO catalyst. In particular, the relative unit health risk associated with the decrease in emissions of airborne toxic compounds using unleaded Chinese fuel was reduced from 6.33 to 0.30. (Use of low-sulfur California Phase II gasoline rather than current in-use Chinese fuel reduced emissions further.) Following implementation of the program, a follow-up study showed that in-use emissions benefits were considerably less than anticipated, primarily because of poor quality control at the retrofit service centers, a less aggressive preretrofit maintenance procedure, and unauthorized modification to the recommended retrofit control system. Overall results indicate that a carefully controlled retrofit program using REO catalyst technology can reduce emissions significantly. However, well-defined implementation guidelines, and strict adherence to these guidelines are needed to achieve maximum benefits.

Evaluation of several biological monitoring techniques for hazard assessment of potentially contaminated wastewater and groundwater. Volume 3. Old O-field groundwater. Final report, July 1990-December 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burton, D.T.; Turley, S.D.

1992-03-01

The toxicity of contaminated Old O-Field (Edgewood Area of Aberdeen Proving Ground) groundwater and the reduction and/or elimination of toxicity by various treatment processes were evaluated. The study was divided into a bench scale and pilot scale study. The bench scale studies consisted of 48-h definitive acute toxicity tests run with daphnid neonates (Daphnia magna) and juvenile fathead minnows (Pimephales promelas) exposed to untreated Old O-Field groundwater and groundwater treated by metals precipitation, UV oxidation (H 2O2 ), carbon adsorption, and carbon adsorption/biological sludge. The pilot scale studies consisted of several 96-h definitive acute toxicity tests run with two freshwatermore » and two saltwater invertebrates and fish and Ames mutagenicity assays. Acute toxicity tests were run on untreated Old O-Field groundwater and groundwater treated by metals precipitation, UV oxidation (H2O2), air stripping, and carbon adsorption during the pilot scale study. The freshwater invertebrate and fish used in the study were daphnid neonates and juvenile fathead minnows, respectively. The saltwater invertebrate and fish were juvenile mysids (Mysidopsis bahia) and juvenile sheepshead minnows (Cyprinodon variegatus). Ames tests were run on untreated groundwater, UV oxidation-treated groundwater, and carbon-treated groundwater.... Groundwater, Aquatic, Toxicity, Daphnia, Daphnia magna, Fathead minnow, Pimephales promelas, Mysid, Mysidopsis bahia, Sheepshead minnow, Cyprinodon variegatus.« less

Beam Path Toxicities to Non-Target Structures During Intensity-Modulated Radiation Therapy for Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenthal, David I.; Chambers, Mark S.; Fuller, Clifton D.

2008-11-01

Background: Intensity-modulated radiation therapy (IMRT) beams traverse nontarget normal structures not irradiated during three-dimensional conformal RT (3D-CRT) for head and neck cancer (HNC). This study estimates the doses and toxicities to nontarget structures during IMRT. Materials and Methods: Oropharyngeal cancer IMRT and 3D-CRT cases were reviewed. Dose-volume histograms (DVH) were used to evaluate radiation dose to the lip, cochlea, brainstem, occipital scalp, and segments of the mandible. Toxicity rates were compared for 3D-CRT, IMRT alone, or IMRT with concurrent cisplatin. Descriptive statistics and exploratory recursive partitioning analysis were used to estimate dose 'breakpoints' associated with observed toxicities. Results: A totalmore » of 160 patients were evaluated for toxicity; 60 had detailed DVH evaluation and 15 had 3D-CRT plan comparison. Comparing IMRT with 3D-CRT, there was significant (p {<=} 0.002) nonparametric differential dose to all clinically significant structures of interest. Thirty percent of IMRT patients had headaches and 40% had occipital scalp alopecia. A total of 76% and 38% of patients treated with IMRT alone had nausea and vomiting, compared with 99% and 68%, respectively, of those with concurrent cisplatin. IMRT had a markedly distinct toxicity profile than 3D-CRT. In recursive partitioning analysis, National Cancer Institute's Common Toxicity Criteria adverse effects 3.0 nausea and vomiting, scalp alopecia and anterior mucositis were associated with reconstructed mean brainstem dose >36 Gy, occipital scalp dose >30 Gy, and anterior mandible dose >34 Gy, respectively. Conclusions: Dose reduction to specified structures during IMRT implies an increased beam path dose to alternate nontarget structures that may result in clinical toxicities that were uncommon with previous, less conformal approaches. These findings have implications for IMRT treatment planning and research, toxicity assessment, and multidisciplinary patient management.« less

Determination of pharmaceutical compounds in hospital wastewater and their elimination by advanced oxidation processes.

PubMed

Souza, Fernanda S; Da Silva, Vanessa V; Rosin, Catiusa K; Hainzenreder, Luana; Arenzon, Alexandre; Pizzolato, Tania; Jank, Louise; Féris, Liliana A

2018-02-23

This study investigates the mineralization efficiency, i.e. removal of total organic carbon (TOC) in hospital wastewater by direct ozonation, ozonation with UV radiation (O 3 /UV), homogeneous catalytic ozonation (O 3 /Fe 2+ ) and homogeneous photocatalytic ozonation (O 3 /Fe 2+ /UV). The influence of pH and reaction time was evaluated. For the best process, toxicity and degradation efficiency of the selected pharmaceutical compounds (PhCs) were determined. The results showed that the PhCs detected in the hospital wastewater were completely degraded when the mineralization efficiency reached 54.7% for O 3 /UV with 120 minutes of reaction time using a rate of 1.57 g O 3 h -1 . This process also achieved a higher chemical oxygen demand removal efficiency (64.05%), an increased aromaticity reduction efficiency (81%) and a toxicity reduction.

Using risk elasticity to prioritize risk reduction strategies for geographical areas and industry sectors.

PubMed

Li, Pei-Chiun; Ma, Hwong-Wen

2016-01-25

The total quantity of chemical emissions does not take into account their chemical toxicity, and fails to be an accurate indicator of the potential impact on human health. The sources of released contaminants, and therefore, the potential risk, also differ based on geography. Because of the complexity of the risk, there is no integrated method to evaluate the effectiveness of risk reduction. Therefore, this study developed a method to incorporate the spatial variability of emissions into human health risk assessment to evaluate how to effectively reduce risk using risk elasticity analysis. Risk elasticity analysis, the percentage change in risk in response to the percentage change in emissions, was adopted in this study to evaluate the effectiveness and efficiency of risk reduction. The results show that the main industry sectors are different in each area, and that high emission in an area does not correspond to high risk. Decreasing the high emissions of certain sectors in an area does not result in efficient risk reduction in this area. This method can provide more holistic information for risk management, prevent the development of increased risk, and prioritize the risk reduction strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

Biosorption of landfill leachate by Phanerochaete sp. ISTL01: isotherms, kinetics and toxicological assessment.

PubMed

Ghosh, Pooja; Thakur, Indu Shekhar

2017-07-01

The study investigates the ability of fungus Phanerochaete sp. ISTL01 for biosorption of color from landfill leachate. Batch mode experiments were conducted to study the effects of pH, temperature, adsorbent dose, contact time and initial leachate concentration on biosorption. Maximum biosorption capacity was determined as 17.73 mg g -1 of biomass. Equilibrium isotherms and kinetics were further studied. The biosorption data were found to fit well to the Freundlich isotherm and pseudo-second-order kinetic model. The value of activation energy suggested that chemisorption mechanism was involved. Biosorption efficiency was also evaluated by the Methyltetrazolium (MTT) assay for cytotoxicity and alkaline comet assay in HepG2 human hepato-carcinoma cells. The fungus reduced toxicity as shown by 1.3-fold increase in MTT EC 50 and 1.5- and 1.1-fold reduction in Tail moment and Olive tail moment, respectively, after 12 h biosorption. The fungus showed good biosorption characteristics in terms of contaminant-level reduction per unit mass of adsorbent, process kinetics and toxicity reduction, envisaging its application in leachate treatment.

The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

PubMed

Tastekin, Didem; Tambas, Makbule; Kilic, Kemal; Erturk, Kayhan; Arslan, Deniz

2014-12-01

This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.

Evaluation of cytotoxicity, genotoxicity and teratogenicity of marine sediments from Qingdao coastal areas using in vitro fish cell assay, comet assay and zebrafish embryo test.

PubMed

Yang, Fan; Zhang, Qianqian; Guo, Huarong; Zhang, Shicui

2010-10-01

Marine sediments are often a final sink for numerous anthropogenic contaminants and may impose serious effects on benthic organisms and ecosystem. An in vitro cell assay using a cell line derived from flounder gill (FG) cells, an in vitro comet assay in FG cells, and an in vitro zebrafish embryo assay were used to evaluate the in vitro cytotoxicity (measured by MTT reduction), genotoxicity and teratogenicity of crude sediment extracts of Li Cang (LC), Zhan Qiao (ZQ) and Olympic Sailing Center (OSC) from Qingdao coastal area. Sediments from the three sites displayed different cytotoxicity, genotoxicity and teratogenicity potencies; however, all three assays yielded similar LOECs (lowest observed effect concentration) for each site, suggesting that the assays were equally sensitive to and suitable for initial screening of the LOECs of marine sediments. The cytotoxicity, genotoxicity and teratogenicity for these three sampling sites were in the same order of LC>ZQ>OSC, indicating different degrees of contamination. Interestingly, trials with the three sediment extracts at the doses inducing a similar cytotoxicity as evaluated with MTT reduction did not produce similar genotoxicity and teratogenicity, with the genotoxic and teratogenic activities of LC and ZQ extracts being markedly higher than those of OSC sediments. These findings indicate that cytotoxicity does not form a fully equivalent toxicity index with that of genotoxicity and teratogenicity. Therefore, in order to assess the true toxic potential of marine sediments, all three assays should be performed. Analysis of 16 EPA (US Environmental Protection Agency) priority PAHs in these three sediment samples showed a clear correlation between PAH concentrations and sediment toxicities, with a higher PAH content corresponding to higher toxicity although PAHs are surely not the only cause. Copyright © 2010 Elsevier Ltd. All rights reserved.

Identifying potential exposure reduction priorities using regional rankings based on emissions of known and suspected carcinogens to outdoor air in Canada.

PubMed

Setton, Eleanor M; Veerman, Basil; Erickson, Anders; Deschenes, Steeve; Cheasley, Roz; Poplawski, Karla; Demers, Paul A; Keller, C Peter

2015-08-22

Emissions inventories aid in understanding the sources of hazardous air pollutants and how these vary regionally, supporting targeted reduction actions. Integrating information on the relative toxicity of emitted pollutants with respect to cancer in humans helps to further refine reduction actions or recommendations, but few national programs exist in North America that use emissions estimates in this way. The CAREX Canada Emissions Mapping Project provides key regional indicators of emissions (total annual and total annual toxic equivalent, circa 2011) of 21 selected known and suspected carcinogens. The indicators were calculated from industrial emissions reported to the National Pollutant Release Inventory (NPRI) and estimates of emissions from transportation (airports, trains, and car and truck traffic) and residential heating (oil, gas and wood), in conjunction with human toxicity potential factors. We also include substance-specific annual emissions in toxic equivalent kilograms and annual emissions in kilograms, to allow for ranking substances within any region. For provinces and territories in Canada, the indicators suggest the top five substances contributing to the total toxic equivalent emissions in any region could be prioritized for further investigation. Residents of Quebec and New Brunswick may be more at risk of exposure to industrial emissions than those in other regions, suggesting that a more detailed study of exposure to industrial emissions in these provinces is warranted. Residential wood smoke may be an important emission to control, particularly in the north and eastern regions of Canada. Residential oil and gas heating, along with rail emissions contribute little to regional emissions and therefore may not be an immediate regional priority. The developed indicators support the identification of pollutants and sources for additional investigation when planning exposure reduction actions among Canadian provinces and territories, but have important limitations similar to other emissions inventory-based tools. Additional research is required to evaluate how the Emissions Mapping Project is used by different groups and organizations with respect to informing actions aimed at reducing Canadians' potential exposure to harmful air pollutants.

[Comparative toxicity of photosensitizers in varying destruction].

PubMed

Sinitsina, O O; Zholdakova, Z I; Poliakova, E E; Golovach, E N; Sycheva, L P; Beliaeva, N N; Kuznetsova, N A

2007-01-01

The toxicity of the photosensitizers proflavine acetate (PA) versus methylene blue (MB) was evaluated during their varying destruction. Under the influence of visible light, a partial (25%) transformation of the photosensitizers was shown to be attended by their enhanced toxicity and 100% destruction of the parent substances caused a reduction in their hazard. PA and its phototransformation products mainly affect the antiperoxide protection system and the structural and functional states of the liver, kidney, and duodenum. The maximum noneffective dose is 0.002 mg/kg. The possibility of using PA for water disinfection depends on the ratio of safe and effective concentrations. A partial (25%) MB destruction products cause mutagenic effects; the permissible dose of the mutagen is 0.00025 mg/kg. MB is not recommended for disinfection of all types of waters.

Toxicity and biodegradability of selected N-substituted phenols under anaerobic conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donlon, B.; Razo-Flores, E.; Hwu, C.S.

1995-12-31

The anaerobic toxicity and biodegradability of N-substituted aromatics were evaluated in order to obtain information on their ultimate biotreatment. The toxicity of selected N-substituted aromatic compounds toward acetoclastic methanogens in granular sludge was measured in batch assays. This toxicity was highly correlated with compound hydrophobicity, indicating that partitioning into the bacterial membranes was an important factor in the toxicity. However, other factors, such as chemical interactions with key cell components, were suggested to be playing an important role. Nitroaromatic compounds were, on the average, over 300-fold more toxic than their amino-substituted counterparts. This finding suggests that the facile reduction ofmore » nitro-groups known to occur in anaerobic environments would result in a high level of detoxification. To test this hypothesis, continuous lab-scale upward-flow anaerobic sludge bed reactors treating 2-nitrophenol and 4-nitrophenol were established. The 4-nitrophenol was readily converted to the corresponding 4-aminophenol, whereas complete mineralization of 2-nitrophenol via intermediate formation of 2-aminophenol was obtained. These conversions led to a dramatic detoxification of the nitrophenols, because it was feasible to treat the highly toxic nitrophenolics at high organic loading rates.« less

Impact of bio-palladium nanoparticles (bio-Pd NPs) on the activity and structure of a marine microbial community.

PubMed

Nuzzo, Andrea; Hosseinkhani, Baharak; Boon, Nico; Zanaroli, Giulio; Fava, Fabio

2017-01-01

Biogenic palladium nanoparticles (bio-Pd NPs) represent a promising catalyst for organohalide remediation in water and sediments. However, the available information regarding their possible impact in case of release into the environment, particularly on the environmental microbiota, is limited. In this study the toxicity of bio-Pd NPs on the model marine bacterium V. fischeri was assessed. The impacts of different concentrations of bio-Pd NPs on the respiratory metabolisms (i.e. organohalide respiration, sulfate reduction and methanogenesis) and the structure of a PCB-dechlorinating microbial community enriched form a marine sediment were also investigated in microcosms mimicking the actual sampling site conditions. Bio-Pd NPs had no toxic effect on V. fischeri. In addition, they had no significant effects on PCB-dehalogenating activity, while showing a partial, dose-dependent inhibitory effect on sulfate reduction as well as on methanogenesis. No toxic effects by bio-Pd NPs could be also observed on the total bacterial community structure, as its biodiversity was increased compared to the not exposed community. In addition, resilience of the microbial community to bio-Pd NPs exposure was observed, being the final community organization (Gini coefficient) of samples exposed to bio-Pd NPs similar to that of the not exposed one. Considering all the factors evaluated, bio-Pd NPs could be deemed as non-toxic to the marine microbiota in the conditions tested. This is the first study in which the impact of bio-Pd NPs is extensively evaluated over a microbial community in relevant environmental conditions, providing important information for the assessment of their environmental safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-E5103

PubMed Central

Schneider, Bryan P.; Shen, Fei; Jiang, Guanglong; O'Neill, Anne; Radovich, Milan; Li, Lang; Gardner, Laura; Lai, Dongbing; Foroud, Tatiana; Sparano, Joseph A.; Sledge, George W.; Miller, Kathy D.

2017-01-01

Purpose Racial disparity in breast cancer outcomes exists between African American and Caucasian women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for breast cancer patients in the context of a randomized, phase III adjuvant trial. Patients and Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial; ECOG-ACRIN-E5103. The primary efficacy endpoint, invasive disease free survival (DFS) and clinically significant toxicities were compared including: anthracycline-induced congestive heart failure (CHF), taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS (p=0.002; HR=1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (p=0.03); with a similar, non-significant trend for those who had triple negative breast cancer (TNBC; p=0.12). AAs also had significantly more grade 3-4 TIPN (OR=2.9; p=2.4 ×10-11) and grade 3-4 bevacizumab-induced hypertension (OR=1.6; p=0.02), with a trend for more CHF (OR=1.8; p=0.08). AAs had significantly more dose reductions for paclitaxel (p=6.6 ×10-6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS (p=0.03); whereas in EAs, dose reductions did not impact outcome (p=0.35). Conclusion AAs had inferior DFS with more clinically important toxicities in ECOG-ACRIN-E5103. The altered risk to benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus centered on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions for paclitaxel, especially due to TIPN, are warranted for this population. PMID:29333527

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study

PubMed Central

Gawron, Michal; Smith, Danielle M.; Peng, Margaret; Jacob, Peyton; Benowitz, Neal L.

2017-01-01

Introduction: Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. Methods: We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. Results: In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. Conclusions: After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. Implications: To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device. PMID:27613896

Exposure to Nicotine and Selected Toxicants in Cigarette Smokers Who Switched to Electronic Cigarettes: A Longitudinal Within-Subjects Observational Study.

PubMed

Goniewicz, Maciej L; Gawron, Michal; Smith, Danielle M; Peng, Margaret; Jacob, Peyton; Benowitz, Neal L

2017-02-01

Electronic cigarettes (e-cigarettes) are purported to deliver nicotine aerosol without any toxic combustion products present in tobacco smoke. In this longitudinal within-subjects observational study, we evaluated the effects of e-cigarettes on nicotine delivery and exposure to selected carcinogens and toxicants. We measured seven nicotine metabolites and 17 tobacco smoke exposure biomarkers in the urine samples of 20 smokers collected before and after switching to pen-style M201 e-cigarettes for 2 weeks. Biomarkers were metabolites of 13 major carcinogens and toxicants in cigarette smoke: one tobacco-specific nitrosamine (NNK), eight volatile organic compounds (1,3-butadiene, crotonaldehyde, acrolein, benzene, acrylamide, acrylonitrile, ethylene oxide, and propylene oxide), and four polycyclic aromatic hydrocarbons (naphthalene, fluorene, phenanthrene, and pyrene). Changes in urine biomarkers concentration were tested using repeated measures analysis of variance. In total, 45% of participants reported complete abstinence from cigarette smoking at 2 weeks, while 55% reported continued smoking. Levels of total nicotine and some polycyclic aromatic hydrocarbon metabolites did not change after switching from tobacco to e-cigarettes. All other biomarkers significantly decreased after 1 week of using e-cigarettes (p < .05). After 1 week, the greatest percentage reductions in biomarkers levels were observed for metabolites of 1,3-butadiene, benzene, and acrylonitrile. Total NNAL, a metabolite of NNK, declined by 57% and 64% after 1 and 2 weeks, respectively, while 3-hydroxyfluorene levels declined by 46% at week 1, and 34% at week 2. After switching from tobacco to e-cigarettes, nicotine exposure remains unchanged, while exposure to selected carcinogens and toxicants is substantially reduced. To our knowledge, this is the first study that demonstrates that substituting tobacco cigarettes with an e-cigarette may reduce user exposure to numerous toxicants and carcinogens otherwise present in tobacco cigarettes. Data on reduced exposure to harmful constituents that are present in tobacco cigarettes and e-cigarettes can aid in evaluating e-cigarettes as a potential harm reduction device. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fate and abundance of classical and heteroatomic naphthenic acid species after advanced oxidation processes: Insights and indicators of transformation and degradation.

PubMed

Meshref, Mohamed N A; Chelme-Ayala, Pamela; Gamal El-Din, Mohamed

2017-11-15

The toxicological effects from all components in oil sands process-affected water (OSPW) are not known. Alternatively, monitoring the variations and abundance of different classes and compounds after treatments might be a useful approach in OSPW remediation. In this study, the variations in the compositions of classical and heteroatomic naphthenic acids (NAs) after treatment using advanced oxidation processes (AOPs), mainly ozone and peroxone, and two different mass spectrometry methods; ultra-performance liquid chromatography time-of-flight (UPLC-TOFMS) and Fourier transform ion cyclotron resonance (FTICR-MS), were examined. Two markers (O 2 S:O 3 S:O 4 S and O 2 :O 4 ratios) were used to reveal changes and similarities of the treated water characteristics with those in natural waters. Both ratios decreased after all treatments, from 2.7:4.8:2.1 and 3.59 in raw OSPW to 0:1.4:0.5 and 0.7, respectively, in peroxone (1:2), becoming close to the reported ratios in natural waters. Toxicity toward Vibrio fischeri showed residual toxic effects after AOPs, suggesting that part of OSPW toxicity may be caused by specific compounds of NAs (i.e., similar reduction (50%) was achieved in both toxicity and abundance in O 2 species with carbon 15-26) and/or generated by-products (e.g., O 3 S classes at double bond equivalent (DBE) = 4 and C 9 H 12 O 2 at DBE = 4). Although by-products were generated, the best biodegradability enhancement and chemical oxygen demand reduction were achieved in peroxone (1:2) compared to ozone, suggesting the possibility of using combined OSPW remediation approaches (i.e., peroxone coupled with biological process). The recommended indicators can assist in evaluating the treatments' performance and in examining the best removal levels to accomplish significant toxicity reduction. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tobacco Smoke–Related Health Effects Induced by 1,3-Butadiene and Strategies for Risk Reduction

PubMed Central

Soeteman-Hernández, Lya G.

2013-01-01

1,3-Butadiene (BD) is a smoke component selected by the World Health Organization (WHO) study group on Tobacco Product Regulation (TobReg) for mandated lowering. We examined the tobacco smoke–related health effects induced by BD and possible health impacts of risk reduction strategies. BD levels in mainstream smoke (MSS) from international and Canadian cigarettes and environmental tobacco smoke (ETS) were derived from scientific journals and international government reports. Dose-response analyses from toxicity studies from government reports were evaluated and the most sensitive cancer and noncancer endpoints were selected. The risks were evaluated by taking the ratio (margin of exposure, MOE) from the most sensitive toxicity endpoint and appropriate exposure estimates for BD in MSS and ETS. BD is a good choice for lowering given that MSS and ETS were at levels for cancer (leukemia) and noncancer (ovarian atrophy) risks, and the risks can be significantly lowered when lowering the BD concentrations in smoke. Several risk reduction strategies were analyzed including a maximum level of 125% of the median BD value per milligram nicotine obtained from international brands as recommended by the WHO TobReg, tobacco substitute sheets, dual and triple carbon filters, and polymer-derived carbon. The use of tobacco substitute sheet with a polymer-derived carbon filter resulted in the most significant change in risk for cancer and noncancer effects. Our results demonstrate that MOE analysis might be a practical way to assess the impact of risk reduction strategies on human health in the future. PMID:24014643

Reduction of Sodium Arsenite-Mediated Adverse Effects in Mice using Dietary Supplementation of Water Hyacinth (Eichornia crassipes) Root Powder.

PubMed

Sarker, Rim Sabrina Jahan; Ahsan, Nazmul; Hossain, Khaled; Ghosh, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Akhand, Anwarul Azim

2012-07-01

In this study, we evaluated the protective effects of water Hyacinth Root Powder (HRP) on arsenic-mediated toxic effects in mice. Swiss albino mice, used in this study, were divided into four different groups (for each group n=5). The control group was supplied with normal feed and water, Arsenic group (As-group) was supplied with normal feed plus arsenic (sodium arsenite)-containing water, and arsenic+hyacinth group (As+Hy group) was supplied with feed supplemented with HRP plus arsenic water. The remaining Hy-group was supplied with feed supplemented with HRP plus normal water. Oral administration of arsenic reduced the normal growth of the mice as evidenced by weight loss. Interestingly, tip of the tails of these mice developed wound that caused gradual reduction of the tail length. Supplementation of HRP in feed significantly prevented mice growth retardation and tail wounding in As+Hy group mice. However, the growth pattern in Hy-group mice was observed to be almost similar to that of the control group indicating that HRP itself has no toxic or negative effect in mice. Ingested arsenic also distorted the shape of the blood cells and elevated the serum enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and serum glutamic pyruvic transaminase (SGPT). Importantly, elevation of these enzymes and distortion of blood cell shape were partially reduced in mice belong to As+Hy group, indicating HRP-mediated reduction of arsenic toxicity. Therefore, the preventive effect of hyacinth root on arsenic-poisoned mice suggested the future application of hyacinth to reduce arsenic toxicity in animal and human.

Reduction of Sodium Arsenite-Mediated Adverse Effects in Mice using Dietary Supplementation of Water Hyacinth (Eichornia crassipes) Root Powder

PubMed Central

Sarker, Rim Sabrina Jahan; Ahsan, Nazmul; Hossain, Khaled; Ghosh, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Akhand, Anwarul Azim

2012-01-01

Background In this study, we evaluated the protective effects of water Hyacinth Root Powder (HRP) on arsenic-mediated toxic effects in mice. Methods Swiss albino mice, used in this study, were divided into four different groups (for each group n=5). The control group was supplied with normal feed and water, Arsenic group (As-group) was supplied with normal feed plus arsenic (sodium arsenite)-containing water, and arsenic+hyacinth group (As+Hy group) was supplied with feed supplemented with HRP plus arsenic water. The remaining Hy-group was supplied with feed supplemented with HRP plus normal water. Results Oral administration of arsenic reduced the normal growth of the mice as evidenced by weight loss. Interestingly, tip of the tails of these mice developed wound that caused gradual reduction of the tail length. Supplementation of HRP in feed significantly prevented mice growth retardation and tail wounding in As+Hy group mice. However, the growth pattern in Hy-group mice was observed to be almost similar to that of the control group indicating that HRP itself has no toxic or negative effect in mice. Ingested arsenic also distorted the shape of the blood cells and elevated the serum enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and serum glutamic pyruvic transaminase (SGPT). Importantly, elevation of these enzymes and distortion of blood cell shape were partially reduced in mice belong to As+Hy group, indicating HRP-mediated reduction of arsenic toxicity. Conclusion Therefore, the preventive effect of hyacinth root on arsenic-poisoned mice suggested the future application of hyacinth to reduce arsenic toxicity in animal and human. PMID:23407303

Degradation of bisphenol A and acute toxicity reduction by different thermo-tolerant ascomycete strains isolated from arid soils.

PubMed

Mtibaà, Rim; Olicón-Hernández, Dario Rafael; Pozo, Clementina; Nasri, Moncef; Mechichi, Tahar; González, Jesus; Aranda, Elisabet

2018-07-30

Four different laccase-producing strains were isolated from arid soils and used for bisphenol A (BPA) degradation. These strains were identified as Chaetomium strumarium G5I, Thielavia arenaria CH9, Thielavia arenaria HJ22 and Thielavia arenaria SM1(III) by internal transcribed spacer 5.8 S rDNA analysis. Residual BPA was evaluated by HPLC analysis during 48 h of incubation. A complete removal of BPA was observed by the whole cell fungal cultures within different times, depending on each strain. C. strumarium G5I was the most efficient degrader, showing 100% of removal within 8 h of incubation. The degradation of BPA was accompanied by the production of laccase and dye decolorizing peroxidase (DyP) under degradation conditions. The presence of aminobenzotriazole (ABT) as an inhibitor of cytochrome P450s monooxygenases (CYP) demonstrated a slight decrease in BPA removal rate, suggesting the effective contribution of CYP in the conversion. The great involvement of laccase in BPA transformation together with cell-associated enzymes, such as CYP, was supported by the identification of hydroxylated metabolites by ultra-high performance liquid chromatography-mass spectroscopy (UHPLC-MS). The metabolic pathway of BPA transformation was proposed based on the detected metabolites. The acute toxicity of BPA and its products was investigated and showed a significant reduction, except for T. arenaria SM1(III) that did not caused reduction of toxicity (IC 50 < 8%), possibly due to the presence of toxic metabolites. The results of the present study point out the potential application of the isolated ascomycetes in pollutant removal processes, especially C. strumarium G5I as an efficient degrader of BPA. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of abiotic factors on the mercury reduction process by humic acids in aqueous systems

USDA-ARS?s Scientific Manuscript database

Mercury (Hg) in the environment can have serious toxic effects on a variety of living organisms, and is a pollutant of concern worldwide. The reduction of mercury from the toxic Hg2+ form to Hg0 is especially important. One pathway for this reduction to occur is through an abiotic process with humic...

Acute and early life stage toxicity of industrial effluent on Japanese medaka (Oryzias latipes).

PubMed

Zha, Jinmiao; Wang, Zijian

2006-03-15

To develop the whole effluent toxicity testing methods (WET), embryo larval stage toxicity test using Japanese medaka (Oryzias latipes) was conducted to evaluate an effluent from a banknote printing plant (BPP). The method is based on acute toxicity using endpoint of 96-h larval morality and on chronic toxicity using endpoints such as the time to hatch, hatching success, deformity, growth rate, swim-up failure, accumulative mortality and sexual ratio. In test for 96-h larval mortality, LC50 (the concentration was lethal to 50% of newly hatching medaka larvae) was 72.9%. In chronic toxicity test, newly fertilized embryos (<5-h old) were exposed to 1%, 6.25%, 12.5%, 25%, 50% effluent concentrations and to 200 mug/l BPA in a 24-h static renewal system at 25+/-1 degrees C until 15 day post-hatch. The results showed that all chronic endpoints were significantly different from the control at 50% dilution (p < 0.01). Embryos began to show lesions on 4th day at higher concentrations (12.5%, 25%, 50% BPP effluent concentrations). Treatment group of 25% dilution showed delayed time to hatch. A reduction in body weight was observed at 25% dilutions for males and females, respectively. Deformities were observed in newly hatched larvae at 25% and 50% BPP effluent concentrations. At 25% dilution, sex ratio of larvae was alternated and there was feminization phenomenon. We conclude that embryo larval stage test using medaka is feasible to evaluate both acute and chronic toxicities and potential endocrine disrupting activity of industrial effluents.

Nanoparticles Made From Xyloglucan-Block-Polycaprolactone Copolymers: Safety Assessment for Drug Delivery.

PubMed

Mazzarino, Letícia; Loch-Neckel, Gecioni; Dos Santos Bubniak, Lorena; Ourique, Fabiana; Otsuka, Issei; Halila, Sami; Curi Pedrosa, Rozangela; Santos-Silva, Maria Cláudia; Lemos-Senna, Elenara; Curti Muniz, Edvani; Borsali, Redouane

2015-09-01

Xyloglucan-block-polycaprolactone (XGO-PCL) copolymer nanoparticles have been proposed as nanocarriers for drug delivery. However, the possible harmful effects of exposure to nanoparticles still remain a concern. Therefore, the aim of this study is to evaluate the potential toxicity of XGO-PCL nanoparticles using in vitro and in vivo assays. Cytotoxicity and genotoxicity studies were conducted on MRC-5 human fetal lung fibroblast cells upon exposure to XGO-PCL nanoparticles. No significant reduction in the cell viability and no DNA damage were observed at the different concentrations tested. Erythrocyte toxicity was assessed by the incubation of nanoparticles with human blood. XGO-PCL nanoparticles induced a hemolytic ratio of less than 1%, indicating good blood compatibility. Finally, the subacute toxicity of XGO-PCL nanoparticles (10 mg/kg/day) was evaluated in BALB/c mice when administered orally or intraperitoneally for 14 days. Results of the in vivo toxicity study showed no clinical signs of toxicity, mortality, weight loss, or hematological and biochemical alterations after treatment with nanoparticles. Also, microscopic analysis of the major organs revealed no histopathological abnormalities, corroborating the previous results. Thus, it can be concluded that XGO-PCL nanoparticles induced no effect indicative of toxicity, indicating their potential use as drug delivery systems. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Monofluorophosphate is a selective inhibitor of respiratory sulfate-reducing microorganisms.

PubMed

Carlson, Hans K; Stoeva, Magdalena K; Justice, Nicholas B; Sczesnak, Andrew; Mullan, Mark R; Mosqueda, Lorraine A; Kuehl, Jennifer V; Deutschbauer, Adam M; Arkin, Adam P; Coates, John D

2015-03-17

Despite the environmental and economic cost of microbial sulfidogenesis in industrial operations, few compounds are known as selective inhibitors of respiratory sulfate reducing microorganisms (SRM), and no study has systematically and quantitatively evaluated the selectivity and potency of SRM inhibitors. Using general, high-throughput assays to quantitatively evaluate inhibitor potency and selectivity in a model sulfate-reducing microbial ecosystem as well as inhibitor specificity for the sulfate reduction pathway in a model SRM, we screened a panel of inorganic oxyanions. We identified several SRM selective inhibitors including selenate, selenite, tellurate, tellurite, nitrate, nitrite, perchlorate, chlorate, monofluorophosphate, vanadate, molydate, and tungstate. Monofluorophosphate (MFP) was not known previously as a selective SRM inhibitor, but has promising characteristics including low toxicity to eukaryotic organisms, high stability at circumneutral pH, utility as an abiotic corrosion inhibitor, and low cost. MFP remains a potent inhibitor of SRM growing by fermentation, and MFP is tolerated by nitrate and perchlorate reducing microorganisms. For SRM inhibition, MFP is synergistic with nitrite and chlorite, and could enhance the efficacy of nitrate or perchlorate treatments. Finally, MFP inhibition is multifaceted. Both inhibition of the central sulfate reduction pathway and release of cytoplasmic fluoride ion are implicated in the mechanism of MFP toxicity.

Act on the Registration and Evaluation of Chemicals (K-REACH) and replacement, reduction or refinement best practices

PubMed Central

2016-01-01

Objectives Korea’s Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. Methods Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory documents regarding the limitation of animal experiments and its alternatives in order to discuss the regulatory adoption of alternative tests. Results Depending on the tonnage of the chemical used, the data required ranges from acute and other short-term studies for a single exposure route to testing via multiple exposure routes and costly, longer-term studies such as a full two-generation reproducibility toxicity. The European Registration, Evaluation, Authorization and Restriction of Chemicals regulation provides for mandatory sharing of vertebrate test data to avoid unnecessary duplication of animal use and test costs, and obligation to revise data requirements and test guidelines “as soon as possible” after relevant, validated replacement, reduction or refinement (3R) methods become available. Furthermore, the Organization for Economic Cooperation and Development actively accepts alternative animal tests and 3R to chemical toxicity tests. Conclusions Alternative tests which are more ethical and efficient than animal experiments should be widely used to assess the toxicity of chemicals for K-REACH registration. The relevant regulatory agencies will have to make efforts to actively adopt and uptake new alternative tests and 3R to K-REACH. PMID:28118702

Randomized phase III trial of postoperative radiochemotherapy +/- amifostine in head and neck cancer. Is there evidence for radioprotection?

PubMed

Vacha, Peter; Fehlauer, Fabian; Mahlmann, Birgit; Marx, Meinolf; Hinke, Axel; Sommer, Konrad; Richter, Eckart; Feyerabend, Thomas

2003-06-01

Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine (A). We investigated this issue in a randomized trial comparing radiochemotherapy (RT + CT) versus radiochemotherapy plus amifostine (RC + CT + A) in patients with head and neck cancer. 56 patients with oro-/hypopharynx or larynx cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RC + CT alone or RC + CT + A. Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2) and received chemotherapy (70 mg/m(2) carboplatin, day 1-5 in week 1 and 5 of radiotherapy). 250 mg amifostine were applied daily before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for acute xerostomia, patients with laryngeal cancer were excluded from evaluation. 50 patients were evaluable (25 patients in the RC + CT, 25 patients in the RC + CT + A group). Clinical characteristics were well balanced in both treatment groups. Amifostine provided reduction in acute xerostomia and mucositis but had no obvious influence on Karnofsky performance status, body weight, cutaneous side effects, and alopecia. The differences between both groups were statistically significant for acute xerostomia and nonsignificant, but with a trend for mucositis. According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary.

Predictors of Long-Term Toxicity Using Three-Dimensional Conformal External Beam Radiotherapy to Deliver Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shaitelman, Simona F.; Kim, Leonard H.; Grills, Inga S.

Purpose: We analyzed variables associated with long-term toxicity using three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation. Methods and Materials: One hundred patients treated with 3D-CRT accelerated partial breast irradiation were evaluated using Common Terminology Criteria for Adverse Events version 4.0 scale. Cosmesis was scored using Harvard criteria. Multiple dosimetric and volumetric parameters were analyzed for their association with worst and last (W/L) toxicity outcomes. Results: Sixty-two patients had a minimum of 36 months of toxicity follow-up (median follow-up, 4.8 years). The W/L incidence of poor-fair cosmesis, any telangiectasia, and grade {>=}2 induration, volume reduction,more » and pain were 16.4%/11.5%, 24.2%/14.5%, 16.1%/9.7%, 17.7%/12.9%, and 11.3%/3.2%, respectively. Only the incidence of any telangiectasia was found to be predicted by any dosimetric parameter, with the absolute breast volume receiving 5% to 50% of the prescription dose (192.5 cGy-1925 cGy) being significant. No associations with maximum dose, volumes of lumpectomy cavity, breast, modified planning target volume, and PTV, dose homogeneity index, number of fields, and photon energy used were identified with any of the aforementioned toxicities. Non-upper outer quadrant location was associated with grade {>=}2 volume reduction (p = 0.02 W/p = 0.04 L). A small cavity-to-skin distance was associated with a grade {>=}2 induration (p = 0.03 W/p = 0.01 L), a borderline significant association with grade {>=}2 volume reduction (p = 0.06 W/p = 0.06 L) and poor-fair cosmesis (p = 0.08 W/p = 0.09 L), with threshold distances ranging from 5 to 8 mm. Conclusions: No dose--volume relationships associated with long-term toxicity were identified in this large patient cohort with extended follow-up. Cosmetic results were good-to-excellent in 88% of patients at 5 years.« less

Developmental toxicity evaluation of unleaded gasoline vapor in the rat.

PubMed

Roberts, L; White, R; Bui, Q; Daughtrey, W; Koschier, F; Rodney, S; Schreiner, C; Steup, D; Breglia, R; Rhoden, R; Schroeder, R; Newton, P

2001-01-01

To evaluate the potential of unleaded gasoline vapor for developmental toxicity, a sample was prepared by slowly heating API 94-02 (1990 industry average gasoline) and condensing the vapor. The composition of this vapor condensate, which comprises 10.4% by volume of the starting gasoline, is representative of real-world exposure to gasoline vapor encountered at service stations and other occupational settings and consists primarily of volatile short chain (C4-C6) aliphatic hydrocarbons (i.e. paraffins) with small amounts of cycloparaffins and aromatic hydrocarbons. A preliminary study in rats and mice resulted in no developmental toxicity in either species. However, a slight reduction in maternal body weight gain in rats led to the selection of rats for this guideline study. Groups of pregnant rats (n = 24/group) were exposed to unleaded gasoline vapor at concentrations of 0, 1000, 3000, or 9000 (75% lower explosive limit) ppm equivalent to 0, 2653, 7960, or 23,900 mg/m3, for 6 h/day on gestation days 6-19. All rats were sacrificed on gestation day 20. No maternal toxicity was observed. Developmentally, there were no differences between treated and control groups in malformations, total variations, resorptions, fetal body weight, or viability. The maternal and developmental NOAEL is 9000 ppm. Under conditions of this study, unleaded gasoline vapors did not produce evidence of developmental toxicity.

Re-irradiation: outcome, cumulative dose and toxicity in patients retreated with stereotactic radiotherapy in the abdominal or pelvic region.

PubMed

Abusaris, Huda; Hoogeman, M; Nuyttens, Joost J

2012-12-01

The purpose of the present study was to explore the outcome, cumulative dose in tumor and organs at risk and toxicity after extra-cranial stereotactic re-irradiation. Twenty-seven patients were evaluated who had been re-irradiated with stereotactic body radiotherapy (SBRT) after conventional radiotherapy (CRT). The dose summation of the SBRT and CRT plans was done by dose point calculations accounting for fraction size by the linear-quadratic model. Efficacy and toxicity was scored by looking at the reduction in tumor size, pain and bleeding. Symptomatic response was observed in 96% of the patients. The median maximum SBRT dose to the tumor was 90 Gy(3) (range: 42-420 Gy(3)). The median cumulative dose for the rectum, bowel and bladder resulted in 104 Gy(3), 98 Gy(3) and 113 Gy(3), respectively. No grades 5, 4 and 3 acute and late toxicity was observed. re-irradiation to the same region using extra-cranial stereotactic radiotherapy is feasible and resulted in a 96% symptomatic response with low toxicity.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens.

PubMed

Morgens, David W; Wainberg, Michael; Boyle, Evan A; Ursu, Oana; Araya, Carlos L; Tsui, C Kimberly; Haney, Michael S; Hess, Gaelen T; Han, Kyuho; Jeng, Edwin E; Li, Amy; Snyder, Michael P; Greenleaf, William J; Kundaje, Anshul; Bassik, Michael C

2017-05-05

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens.

Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens

PubMed Central

Morgens, David W.; Wainberg, Michael; Boyle, Evan A.; Ursu, Oana; Araya, Carlos L.; Tsui, C. Kimberly; Haney, Michael S.; Hess, Gaelen T.; Han, Kyuho; Jeng, Edwin E.; Li, Amy; Snyder, Michael P.; Greenleaf, William J.; Kundaje, Anshul; Bassik, Michael C.

2017-01-01

CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this library has excellent performance in identifying genes affecting growth and sensitivity to the ricin toxin. The safe-targeting guides allow for proper control of toxicity from on-target DNA damage. Using this toxicity as a proxy to measure off-target cutting, we demonstrate with tens of thousands of guides both the nucleotide position-dependent sensitivity to single mismatches and the reduction of off-target cutting using truncated guides. Our results demonstrate a simple strategy for high-throughput evaluation of target specificity and nuclease toxicity in Cas9 screens. PMID:28474669

The effect of suspended particles coated by humic acid on the toxicity of pharmaceuticals, estrogens, and phenolic compounds.

PubMed

Ra, Jin Sung; Oh, Seok-Young; Lee, Byung Cheun; Kim, Sang Don

2008-02-01

The sorption characteristics of 10 organic chemicals, categorized as pharmaceuticals, estrogens and phenols, onto synthetic suspended particle (i.e., alumina) coated with humic acid were investigated according to their octanol-water partition coefficient (K(ow)). Chemical analyses were performed with gas chromatography and mass spectrometry (GC/MS) and high performance liquid chromatography (HPLC). The effects of particles on the toxicity reduction were evaluated using bioassay tests, using Daphnia magna and Vibrio fisheri for phenols and pharmaceuticals, and the human breast cancer cell MCF-7 for estrogens. Sorption studies revealed that 22 and 38% of octylphenol and pentachlorophenol, respectively, were removed by suspended particle, whereas 2,4-dichlorophenol was not removed, which was directly proportional to the logK(ow) value. Similar to the sorption tests, suspended particles significantly reduced the acute toxicities of octylphenol and pentachlorophenol to D. magna and V. fisheri (p<0.01), but there was no significant difference in the toxicity of 2,4-dichlorophenol to D. magna (p=0.8374). Pharmaceuticals, such as ibuprofen, gemfibrozil and tolfenamic acid, showed no discernible sorption to the suspended particle, with the exception of diclofenac, which revealed 11% sorption. For estrogens, such as estrone, 17beta-estradiol and 17alpha-ethynylestradiol, the results indicated no reduction in the sorption test. This may be attributed to the polar interaction by functional groups in sorption between pharmaceuticals and estrogens and suspended particles. In the bioassays, presence of suspended particles did not significantly modify the toxicity of pharmaceuticals (regardless of their K(ow) values) to D. magna, V. fisheri or E-screen.

Community-Scale Air Toxics Ambient Monitoring Grant - Closed Announcement FY 2015

EPA Pesticide Factsheets

Grant to fund projects designed to assist state, local and tribal communities in identifying air toxics sources, characterizing the degree and extent of local-scale air toxics problems, tracking progress of air toxics reduction activities, etc.

Tooele Army Depot - North Area. Feasibility Study for Operable Units 5, 6, 7, and 10

DTIC Science & Technology

1994-03-01

effectiveness of alternatives in maintaining protection of human health and the environment after response objectives have been met. 4. Reduction of toxicity...Institutional controls may be effective at protecting human health and the environment and complying with ARARs if the site contaminants have low toxicity...reduction of the toxicity, mobility, or volume of soil contaminants through treatment under this alternative. Short-term effectiveness . Human health

Effect of chemical amendments on remediation of potentially toxic trace elements (PTEs) and soil quality improvement in paddy fields.

PubMed

Kim, Sung Chul; Hong, Young Kyu; Oh, Se Jin; Oh, Seung Min; Lee, Sang Phil; Kim, Do Hyung; Yang, Jae E

2017-04-01

Remediation of potentially toxic trace elements (PTEs) in paddy fields is fundamental for crop safety. In situ application of chemical amendments has been widely adapted because of its cost-effectiveness and environmental safety. The main purpose of this research was to (1) evaluate the reduction in dissolved concentrations of cadmium (Cd) and arsenic (As) with the application of chemical amendments and (2) monitor microbial activity in the soil to determine the remediation efficiency. Three different chemical amendments, lime stone, steel slag, and acid mine drainage sludge, were applied to paddy fields, and rice (Oryza sativa L. Milyang 23) was cultivated. The application of chemical amendments immobilized both Cd and As in soil. Between the two PTEs, As reduction was significant (p < 0.05) with the addition of chemical amendments, whereas no significant reduction was observed for Cd than that for the control. Among six soil-related variables, PTE concentration showed a negative correlation with soil pH (r = -0.70 for As and r = -0.54 for Cd) and soil respiration (SR) (r = -0.88 for As and r = -0.45 for Cd). This result indicated that immobilization of PTEs in soil is dependent on soil pH and reduces PTE toxicity. Overall, the application of chemical amendments could be utilized for decreasing PTE (As and Cd) bioavailability and increasing microbial activity in the soil.

Effect of biochar activation by different methods on toxicity of soil contaminated by industrial activity.

PubMed

Kołtowski, Michał; Charmas, Barbara; Skubiszewska-Zięba, Jadwiga; Oleszczuk, Patryk

2017-02-01

The objective of the study was to determine the effect of various methods of biochar activation on the ecotoxicity of soils with various properties and with various content and origin of contaminants. The biochar produced from willow (at 700°C) was activated by 1) microwaves (in a microwave reactor under an atmosphere of water vapour), 2) carbon dioxide (in the quartz fluidized bed reactor) and 3) superheated steam (in the quartz fluidized bed reactor). Three different soils were collected from industrial areas. The soils were mixed with biochar and activated biochars at the dose of 5% and ecotoxicological parameters of mixture was evaluated using two solid phase test - Phytotoxkit F (Lepidium sativum) and Collembolan test (Folsomia candida) and one liquid phase test - Microtox® (Vibrio fischeri). Biochar activation had both positive and negative impacts, depending on the activation method, kind of bioassay and kind of soil. Generally, biochar activated by microwaves increased the effectiveness of ecotoxicity reduction relative to non-activated biochars. Whereas, biochar activated with CO 2 most often cause a negative effect manifested by deterioration or as a lack of improvement in relation to non-activated biochar or to non-amended soil. It was also demonstrated that the increase of biochar specific surface area caused a significant reduction of toxicity of water leachates from the studied soils. Effectiveness of the reduction of leachate toxicity was weakened in the presence of dissolved organic carbon in the soil. Copyright © 2016 Elsevier Inc. All rights reserved.

OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.

PubMed

Tweddle, D A; Pinkerton, C R; Lewis, I J; Ellershaw, C; Cole, M; Pearson, A D

2001-01-01

This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age. Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5 mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600 mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was haematological recovery. Seventy out of ninety-five (74%) patients completed seven or more courses and were evaluable for toxicity. Of these 70 patients, 33% had more than three episodes of fever and sepsis, 35% required more than five blood or platelet transfusions, 36% had grade 2 or more gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death. OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age.

[Ecological security of wastewater treatment processes: a review].

PubMed

Yang, Sai; Hua, Tao

2013-05-01

Though the regular indicators of wastewater after treatment can meet the discharge requirements and reuse standards, it doesn't mean the effluent is harmless. From the sustainable point of view, to ensure the ecological and human security, comprehensive toxicity should be considered when discharge standards are set up. In order to improve the ecological security of wastewater treatment processes, toxicity reduction should be considered when selecting and optimizing the treatment processes. This paper reviewed the researches on the ecological security of wastewater treatment processes, with the focus on the purposes of various treatment processes, including the processes for special wastewater treatment, wastewater reuse, and for the safety of receiving waters. Conventional biological treatment combined with advanced oxidation technologies can enhance the toxicity reduction on the base of pollutants removal, which is worthy of further study. For the process aimed at wastewater reuse, the integration of different process units can complement the advantages of both conventional pollutants removal and toxicity reduction. For the process aimed at ecological security of receiving waters, the emphasis should be put on the toxicity reduction optimization of process parameters and process unit selection. Some suggestions for the problems in the current research and future research directions were put forward.

ProTox: a web server for the in silico prediction of rodent oral toxicity

PubMed Central

Drwal, Malgorzata N.; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R.; Preissner, Robert

2014-01-01

Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein–ligand-based pharmacophore models (‘toxicophores’) for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. PMID:24838562

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

PubMed

Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J; Shakespeare, Thomas P

2013-08-01

There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy < 17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

Toxicity reduction in industrial effluents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-01-01

Wastewater treatment technology is undergoing a profound transformation as a result of the fundamental changes in regulations and permit requirements. Established design procedures and criteria which have served the industry well for decades are no longer useful. Toxicity reduction requirements have forced reconsideration of design standards and caused practicing environmental engineers to seek additional training in the biological sciences. Formal academic programs have not traditionally provided the cross-training between biologists and engineers which is necessary to address these issues. This book describes not only the process of identifying the toxicity problem, but also the treatment technologies which are applicable tomore » reduction or elimination of toxicity. The information provided in this book is a compilation of the experience of ECK-ENFELDER INC. in serving the environmental needs of major industry, and the experience of the individual contributors in research and consultations.« less

Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae)

PubMed Central

de Oliveira, Alisson Macário; Mesquita, Matheus da Silva; da Silva, Gabriela Cavalcante; de Oliveira Lima, Edeltrudes; de Medeiros, Paloma Lys; Paiva, Patrícia Maria Guedes; de Souza, Ivone Antônia; Napoleão, Thiago Henrique

2015-01-01

This work evaluated an ethanolic extract from Morus alba leaves for toxicity to Artemia salina, oral toxicity to mice, and antimicrobial activity. Phytochemical analysis revealed the presence of coumarins, flavonoids, tannins, and triterpenes in the extract, which did not show toxicity to A. salina nauplii. No mortality and behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg b.w.) for 14 days. However, animals that received the highest dose showed reduced MCV and MCHC as well as increased serum alkaline phosphatase activity. In treatments with the extract at both 300 and 2000 mg/kg, there was a reduction in number of leukocytes, with decrease in percentage of lymphocytes and increase in proportion of segmented cells. Histopathological analysis of organs from mice treated with the extract at 2000 mg/kg revealed turgidity of contorted tubules in kidneys, presence of leukocyte infiltration around the liver centrilobular vein, and high dispersion of the spleen white pulp. The extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida tropicalis, and Aspergillus flavus. In conclusion, the extract contains antimicrobial agents and was not lethal for mice when ingested; however, its use requires caution because it promoted biochemical, hematological, and histopathological alterations. PMID:26246840

Benzodiazepines and antipsychotic medications for treatment of acute cocaine toxicity in animal models--a systematic review and meta-analysis.

PubMed

Heard, Kennon; Cleveland, Nathan R; Krier, Shay

2011-11-01

There are no controlled human studies to determine the efficacy of benzodiazepines or antipsychotic medications for prevention or treatment of acute cocaine toxicity. The only available controlled data are from animal models and these studies have reported inconsistent benefits. The objective of this study was to quantify the reported efficacy of benzodiazepines and antipsychotic medication for the prevention of mortality due to cocaine poisoning. We conducted a systematic review to identify English language articles describing experiments that compared a benzodiazepine or antipsychotic medication to placebo for the prevention of acute cocaine toxicity in an animal model. We then used these articles in a meta-analysis with a random-effects model to quantify the absolute risk reduction observed in these experiments. We found 10 articles evaluating antipsychotic medications and 15 articles evaluating benzodiazepines. Antipsychotic medications reduced the risk of death by 27% (95% CI, 15.2%-38.7%) compared to placebo and benzodiazepines reduced the risk of death by 52% (42.8%-60.7%) compared to placebo. Both treatments showed evidence of a dose-response effect, and no experiment found a statistically significant increase in risk of death. We conclude that both benzodiazepines and antipsychotic medications are effective for the prevention of lethality from cocaine toxicity in animal models.

Salicytamide: a New Anti-inflammatory Designed Drug Candidate.

PubMed

Guedes, Karen Marinho Maciel; Borges, Rosivaldo Santos; Fontes-Júnior, Enéas Andrade; Silva, Andressa Santa Brigida; Fernandes, Luanna Melo Pereira; Cartágenes, Sabrina Carvalho; Pinto, Ana Carla Godinho; Silva, Mallone Lopes; Queiroz, Luana Melo Diogo; Vieira, José Luís Fernandes; Sousa, Pergentino José Cunha; Maia, Cristiane Socorro Ferraz

2018-04-13

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

Toxicity of silver nanoparticles towards tumoral human cell lines U-937 and HL-60.

PubMed

Barbasz, Anna; Oćwieja, Magdalena; Roman, Maciej

2017-08-01

The toxicity of three types of silver nanoparticles towards histiocytic lymphoma (U-937) and human promyelocytic cells (HL-60) was studied. The nanoparticles were synthesized in a chemical reduction method using sodium borohydride. Trisodium citrate and cysteamine hydrochloride were used to generate a negative and positive nanoparticle surface charge. The evaluation of cell viability, membrane integrity, antioxidant activity and the induction of inflammation were used to evaluate the difference in cellular response to the nanoparticle treatment. The results revealed that the cysteamine-stabilized (positively charged) nanoparticles (SBATE) were the least toxic although they exhibited a similar ion release profile as the unmodified (negatively charged) nanoparticles obtained using sodium borohydride (SBNM). Citrate-stabilized nanoparticles (SBTC) induced superoxide dismutase (SOD) activity in the HL-60 cells and total antioxidant activity in the U-937 cells despite their resistance to oxidative dissolution. The toxicity of SBNM nanoparticles was manifested in the disruption of membrane integrity, decrease in the mitochondrial functions of cells and the induction of inflammation. These findings allowed to conclude that mechanism of silver nanoparticle cytotoxicity is the combination of effects coming from the surface charge of nanoparticles, released silver ions and biological activity of stabilizing agent molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

Phthalate Esters and Reproductive Toxicity** Presentation requested by State of Mass Use Reductions Committee-TURI

EPA Science Inventory

Phthalate esters and reproductive toxicity the presentation described the uses of phthalates, the toxicity to mammals with a focus on reproductive toxicity and the potency of these chemicals to disrupt mammalian reproductive development in utero

Evaluation of Spirulina platensis extract as natural antivirus against foot and mouth disease virus strains (A, O, SAT2)

PubMed Central

Daoud, Hind M.; Soliman, Eman M.

2015-01-01

Aim: This work was aimed to document the antiviral activates of Spirulina platensis extract against foot and mouth disease virus (FMDV) different types to evaluate its replication in Baby Hamster Kidney (BHK) cell culture and in baby mice. Materials and Methods: Cytotoxicity assay studied for S. platensis extract on BHK cells to determine the non-toxic dose. The non-toxic dose of Spirulina extract was mixed with each type of FMDV (A, O, SAT2). Then 10-fold dilutions from each mixture were done. FMDV titer for each type of treated FMDV was calculated to evaluate the antiviral activity of the Spirulina extract against FMDV. Furthermore, old baby Swiss mice were inoculated with 0.1 ml intraperitonially from the mixture of FMDV different types and different concentration of Spirulina extracts. After 48 h post inoculation, all the baby mice examined to evaluate the antiviral action of Spirulina extract. Results: The result showed that the non-toxic doses of S. platensis (50 ug/ml) revealed 35.7%, 28.5%, and 31% reductions in FMDV titers Type O, A, and SAT2 on BHK cells, respectively. The same non-toxic dose gave 50% of the inhibitory concentration in baby mice without cytotoxic effect. Conclusion: This study confirmed the biological activity of the ethanol extract of S. platensis against FMDV Types O, A, and SAT2. From the results, S. platensis could be useful as antiviral lead to limitation of infection among animals during outbreaks but further studies need to evaluate the S. platensis on experimental or natural infected farm animals to establish the effective dose side affected period of treatment of S. platensis. PMID:27047027

Evaluation of Spirulina platensis extract as natural antivirus against foot and mouth disease virus strains (A, O, SAT2).

PubMed

Daoud, Hind M; Soliman, Eman M

2015-10-01

This work was aimed to document the antiviral activates of Spirulina platensis extract against foot and mouth disease virus (FMDV) different types to evaluate its replication in Baby Hamster Kidney (BHK) cell culture and in baby mice. Cytotoxicity assay studied for S. platensis extract on BHK cells to determine the non-toxic dose. The non-toxic dose of Spirulina extract was mixed with each type of FMDV (A, O, SAT2). Then 10-fold dilutions from each mixture were done. FMDV titer for each type of treated FMDV was calculated to evaluate the antiviral activity of the Spirulina extract against FMDV. Furthermore, old baby Swiss mice were inoculated with 0.1 ml intraperitonially from the mixture of FMDV different types and different concentration of Spirulina extracts. After 48 h post inoculation, all the baby mice examined to evaluate the antiviral action of Spirulina extract. The result showed that the non-toxic doses of S. platensis (50 ug/ml) revealed 35.7%, 28.5%, and 31% reductions in FMDV titers Type O, A, and SAT2 on BHK cells, respectively. The same non-toxic dose gave 50% of the inhibitory concentration in baby mice without cytotoxic effect. This study confirmed the biological activity of the ethanol extract of S. platensis against FMDV Types O, A, and SAT2. From the results, S. platensis could be useful as antiviral lead to limitation of infection among animals during outbreaks but further studies need to evaluate the S. platensis on experimental or natural infected farm animals to establish the effective dose side affected period of treatment of S. platensis.

Levels of selected carcinogens and toxicants in vapour from electronic cigarettes.

PubMed

Goniewicz, Maciej Lukasz; Knysak, Jakub; Gawron, Michal; Kosmider, Leon; Sobczak, Andrzej; Kurek, Jolanta; Prokopowicz, Adam; Jablonska-Czapla, Magdalena; Rosik-Dulewska, Czeslawa; Havel, Christopher; Jacob, Peyton; Benowitz, Neal

2014-03-01

Electronic cigarettes, also known as e-cigarettes, are devices designed to imitate regular cigarettes and deliver nicotine via inhalation without combusting tobacco. They are purported to deliver nicotine without other toxicants and to be a safer alternative to regular cigarettes. However, little toxicity testing has been performed to evaluate the chemical nature of vapour generated from e-cigarettes. The aim of this study was to screen e-cigarette vapours for content of four groups of potentially toxic and carcinogenic compounds: carbonyls, volatile organic compounds, nitrosamines and heavy metals. Vapours were generated from 12 brands of e-cigarettes and the reference product, the medicinal nicotine inhaler, in controlled conditions using a modified smoking machine. The selected toxic compounds were extracted from vapours into a solid or liquid phase and analysed with chromatographic and spectroscopy methods. We found that the e-cigarette vapours contained some toxic substances. The levels of the toxicants were 9-450 times lower than in cigarette smoke and were, in many cases, comparable with trace amounts found in the reference product. Our findings are consistent with the idea that substituting tobacco cigarettes with e-cigarettes may substantially reduce exposure to selected tobacco-specific toxicants. E-cigarettes as a harm reduction strategy among smokers unwilling to quit, warrants further study. (To view this abstract in Polish and German, please see the supplementary files online.).

Dietary modulation of parathion-induced neurotoxicity in adult and juvenile rats.

PubMed

Liu, Jing; Karanth, Subramanya; Pope, Carey

2005-06-01

Previous studies indicated that dietary glucose (15% in drinking water) could markedly exacerbate the toxicity of parathion in adult rats. The present study evaluated the effect of consumption of the commonly used sweetener, high fructose corn syrup (HFCS), on parathion toxicity in adult and juvenile rats. Animals were given free access to either water or 15% HFCS in drinking water for a total of 10 days and challenged with parathion (6 or 18 mg/kg, s.c., for juveniles or adults, respectively) on the 4th day. Signs of cholinergic toxicity, body weight and chow/fluid intake were recorded daily. Acetylcholinesterase (AChE) activity and immunoreactivity (AChE-IR) in frontal cortex and diaphragm were measured at 2, 4, and 7 days after parathion. As HFCS was associated with significant reduction in chow intake, adult rats were also pair-fed to evaluate the effect of similar reduced chow intake alone on parathion toxicity. The results indicated that the cholinergic toxicity of parathion was significantly increased by HFCS feeding in both age groups. The excess sugar consumption, however, did not significantly affect parathion-induced AChE inhibition in either tissue or either age group. Enzyme immunoreactivity in frontal cortex was generally not affected in either age group while diaphragm AChE-IR was significantly reduced by parathion and HFCS alone in adult animals at 2 and 4 days timepoints, and more so by the combination of sugar feeding and parathion exposure in both age groups. Food restriction alone did not exacerbate parathion toxicity. While the mechanism(s) remains unclear, we conclude that voluntary consumption of the common sweetener HFCS can markedly amplify parathion acute toxicity in both juvenile and adult rats.

Degradation mechanism and the toxicity assessment in TiO2 photocatalysis and photolysis of parathion.

PubMed

Kim, Tak-Soo; Kim, Jung-Kon; Choi, Kyungho; Stenstrom, Michael K; Zoh, Kyung-Duk

2006-02-01

The photocatalytic degradation of methyl parathion was carried out using a circulating TiO2/UV reactor. The experimental results showed that parathion was more effectively degraded in the photocatalytic condition than the photolysis and TiO2-only condition. With photocatalysis, 10mg/l parathion was completely degraded within 60 min with a TOC decrease exceeding 90% after 150 min. The main ionic byproducts during photocatalysis were measured. The nitrogen from parathion was recovered mainly as NO3-, NO2- and NH4+, 80% of the sulfur as SO4(2-), and less than 5% of the phosphorus as PO4(3-). The organic intermediates 4-nitrophenol and paraoxon were also identified, and these were further degraded. Two different bioassays (Vibrio fischeri and Daphnia magna) were used to test the acute toxicity of solutions treated by photocatalysis and photolysis. A Microtox test using V. fischeri showed that the toxicity, expressed as the relative toxicity (%), was reduced almost completely after 90 min under photocatalysis, whereas only an 83% reduction was achieved with photolysis alone. Another toxicity test using D. magna also showed that the relative toxicity disappeared after 90 min under photocatalysis, whereas there was a 65% reduction in relative toxicity with photolysis alone. The pattern of toxicity reduction parallels the decrease in parathion and TOC concentrations.

Cutaneous toxicity from epidermal growth factor receptor inhibitors: would a subcutaneous desensitization be helpful? Case report.

PubMed

D'Alessio, Andrea; Cecchini, Sara; Di Mauro, Daniela; Geroli, Luca; Villa, Simonetta; Quadri, Antonello; Resta, Davide; Fortugno, Carmelo

2016-11-11

Cetuximab and panitumumab are monoclonal antibody inhibitors that bind the epidermal growth factor receptor (EGFR) currently used in the treatment of metastatic colorectal cancer. The main adverse event related to EGFR inhibitors (EGFR-Is) is cutaneous toxicity, which can cause dosage reduction and interruption of treatment. State-of-the-art management of skin toxicity associated with EGFR-Is therapy involves the topical administration of corticosteroids and oral antibiotics, but is not completely effective in the management of toxicity. Subcutaneous desensitization with increasing concentrations of monoclonal antibodies can induce a tolerance to drug administration and reduce cutaneous adverse effects. To our knowledge, this is the first case in which a reduction or a disappearance of skin toxicity caused by EGFR-Is through subcutaneous desensitization has been achieved. We present cases of 2 Caucasian patients with adenocarcinoma of the colon treated with EGFR-Is who developed severe cutaneous toxicity. A 73-year-old man presented grade 4 skin toxicity of the face and grade 3 skin toxicity of the trunk during treatment with cetuximab. A 68-year-old woman developed G2 rash on the face after the first administration of cetuximab. These patients underwent subcutaneous desensitization with increasing concentrations of EGFR-Is. After this procedure, patients restarted therapy at the optimal dosage with reduction or disappearance of skin toxicity. These cases suggest that by giving rising doses of antibody it is possible to obtain desensitization able to prevent severe cutaneous adverse events in patients treated with EGFR-Is.

The cardiac dose-sparing benefits of deep inspiration breath-hold in left breast irradiation: a systematic review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smyth, Lloyd M, E-mail: lloyd.smyth@epworth.org.au; Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, School of Biomedical Sciences, Nursing and Health Sciences, Monash University, Clayton, Victoria; Knight, Kellie A

Despite technical advancements in breast radiation therapy, cardiac structures are still subject to significant levels of irradiation. As the use of adjuvant radiation therapy after breast-conserving surgery continues to improve survival for early breast cancer patients, the associated radiation-induced cardiac toxicities become increasingly relevant. Our primary aim was to evaluate the cardiac-sparing benefits of the deep inspiration breath-hold (DIBH) technique. An electronic literature search of the PubMed database from 1966 to July 2014 was used to identify articles published in English relating to the dosimetric benefits of DIBH. Studies comparing the mean heart dose of DIBH and free breathing treatmentmore » plans for left breast cancer patients were eligible to be included in the review. Studies evaluating the reproducibility and stability of the DIBH technique were also reviewed. Ten studies provided data on the benefits of DIBH during left breast irradiation. From these studies, DIBH reduced the mean heart dose by up to 3.4 Gy when compared to a free breathing approach. Four studies reported that the DIBH technique was stable and reproducible on a daily basis. According to current estimates of the excess cardiac toxicity associated with radiation therapy, a 3.4 Gy reduction in mean heart dose is equivalent to a 13.6% reduction in the projected increase in risk of heart disease. DIBH is a reproducible and stable technique for left breast irradiation showing significant promise in reducing the late cardiac toxicities associated with radiation therapy.« less

Toxicity testing of polymer materials for dialysis equipment: reconsidering in vivo testing.

PubMed

Sauer, U G; Liebsch, M; Kolar, R

2000-01-01

In fulfilment of the aims of the European Union Biocidal Directive (Directive 98/8/EC), Technical Guidance Documents are currently being compiled. Part I of these Technical Guidance Documents covers data requirements for active substances and biocidal products. The Three Rs principle has been applied in certain parts of the toxicity and ecotoxicity testing scheme for pesticides, such as testing for acute oral toxicity, skin and eye irritation, skin sensitisation, and dermal absorption. Further recommendations on how to proceed with regard to the continuing replacement, reduction and refinement of animal experiments in this field of regulatory testing are included for consideration. In this context, besides stressing the necessity to validate and accept further alternatives, emphasis is placed on providing the possibility of waiving unnecessary tests and on the continuous evaluation of whether certain tests are needed at all. 2000 FRAME.

Differential effect of biochar upon reduction-induced mobility and bioavailability of arsenate and chromate.

PubMed

Choppala, Girish; Bolan, Nanthi; Kunhikrishnan, Anitha; Bush, Richard

2016-02-01

Heavy metals such as chromium (Cr) and arsenic (As) occur in ionic form in soil, with chromate [Cr(VI)] and arsenate As(V) being the most pre-dominant forms. The application of biochar to Cr(VI) and As(V) spiked and field contaminated soils was evaluated on the reduction processes [(Cr(VI) to Cr(III)] and [As(V) to As(III))], and subsequent mobility and bioavailability of both As(V) and Cr(VI). The assays used in this study included leaching, soil microbial activity and XPS techniques. The reduction rate of As(V) was lower than that of Cr(VI) with and without biochar addition, however, supplementation with biochar enhanced the reduction process of As(V). Leaching experiments indicated Cr(VI) was more mobile than As(V). Addition of biochar reversed the effect by reducing the mobility of Cr and increasing that of As. The presence of Cr and As in both spiked and contaminated soils reduced microbial activity, but with the addition of biochar to these soils, the microbial activity increased in the Cr(VI) contaminated soils, while it was further decreased with As(V) contaminated soils. The addition of biochar was effective in mitigating Cr toxicity by reducing Cr(VI) to Cr(III). In contrast, the conversion process of As(V) to As(III) hastened by biochar was not favourable, as As(III) is more toxic in soils. Overall, the presence of functional groups on biochar promotes reduction by providing the electrons required for reduction processes to occur as determined by XPS data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Silver nanoparticles disrupt germline stem cell maintenance in the Drosophila testis

NASA Astrophysics Data System (ADS)

Ong, Cynthia; Lee, Qian Ying; Cai, Yu; Liu, Xiaoli; Ding, Jun; Yung, Lin-Yue Lanry; Bay, Boon-Huat; Baeg, Gyeong-Hun

2016-02-01

Silver nanoparticles (AgNPs), one of the most popular nanomaterials, are commonly used in consumer products and biomedical devices, despite their potential toxicity. Recently, AgNP exposure was reported to be associated with male reproductive toxicity in mammalian models. However, there is still a limited understanding of the effects of AgNPs on spermatogenesis. The fruit fly Drosophila testis is an excellent in vivo model to elucidate the mechanisms underlying AgNP-induced defects in spermatogenesis, as germ lineages can be easily identified and imaged. In this study, we evaluated AgNP-mediated toxicity on spermatogenesis by feeding Drosophila with AgNPs at various concentrations. We first observed a dose-dependent uptake of AgNPs in vivo. Concomitantly, AgNP exposure caused a significant decrease in the viability and delay in the development of Drosophila in a dose-dependent manner. Furthermore, AgNP-treated male flies showed a reduction in fecundity, and the resulting testes contained a decreased number of germline stem cells (GSCs) compared to controls. Interestingly, testes exposed to AgNPs exhibited a dramatic increase in reactive oxygen species levels and showed precocious GSC differentiation. Taken together, our study suggests that AgNP exposure may increase ROS levels in the Drosophila testis, leading to a reduction of GSC number by promoting premature GSC differentiation.

The mucosal toxicity of different benzalkonium chloride analogues evaluated with an alternative test using slugs.

PubMed

Adriaens, E; Dierckens, K; Bauters, T G; Nelis, H J; van Goethem, F; Vanparys, P; Remon, J P

2001-07-01

The objective of this study was to evaluate the mucosal toxicity of different benzalkonium chloride (BAC) analogues using slugs as the alternative test organism. The effect of different BAC analogues on the mucosal tissue of slugs was determined from the protein, lactate dehydrogenase, and alkaline phosphatase released from the foot mucosa after treatment. Additionally, mucus production and reduction in body weight of the slugs were measured. The eye irritation potency of the molecules was evaluated with the Bovine Corneal Opacity and Permeability (BCOP) assay. The antimicrobial activity of the different BAC analogues was also assessed. All BAC analogues induced severe damage to the mucosal epithelium of the slugs, and the irritation increased with decreasing alkyl chain length: BAC-C16 < BAC-C14 < BAC-C12 approximately BAC-mix. A similar ranking was obtained with the BCOP assay for eye irritation. The relative order of activities among the three BAC analogues was the same, i.e., BAC-C14 > or = BAC-C16 > BAC-C12. The BAC-C14 exhibited higher activity than the BAC-mix. The toxicity and activity of BAC analogues depend on the alkyl chain length. The use of BAC-C14 as a conservative agent in pharmaceutical preparations instead of the BAC-mix should be considered.

Evaluation of boric acid sugar baits against Aedes albopictus (Diptera: Culicidae) in tropical environments.

PubMed

Naranjo, Diana P; Qualls, Whitney A; Müller, Gunter C; Samson, Dayana M; Roque, Deborah; Alimi, Temitope; Arheart, Kristopher; Beier, John C; Xue, Rui-De

2013-04-01

Attractive toxic sugar bait (active ingredient, 1% boric acid) was evaluated against Aedes albopictus Skuse populations in the laboratory, semi-field trials, and field trials in residential communities in St. Augustine, Florida. Laboratory evaluations of boric acid sugar baits applied to the plant Pentas lanceolata (Rubiaceae) demonstrated 100 and 92% mortality of A. albopictus at day 7 and 14, respectively. A semi-field study evaluating the bait application to the upperside or topside of leaves resulted in no significant difference on mortality (P>0.05). Overall combined top and bottom boric acid sugar bait application mortality at day 7 was 95% based on leaf bioassays. Field application of the boric acid sugar baits significantly (P<0.05) decreased adult A. albopictus populations up to day 21 post-treatment compared to the pre-treatment population numbers. A significant reduction in oviposition was demonstrated both at day 7 and 14 post-application (P=0.001) as monitored by ovitraps. Attractive toxic sugar bait application in tropical environments demonstrated efficacy, persistence, and feasibility in controlling A. albopictus populations.

Multicenter pilot study of radiochemotherapy as first-line treatment for adults with medulloblastoma (NOA-07).

PubMed

Beier, Dagmar; Proescholdt, Martin; Reinert, Christiane; Pietsch, Torsten; Jones, David T W; Pfister, Stefan M; Hattingen, Elke; Seidel, Clemens; Dirven, Linda; Luerding, Ralf; Reijneveld, Jaap; Warmuth-Metz, Monika; Bonsanto, Matteo; Bremer, Michael; Combs, Stephanie E; Rieken, Stefan; Herrlinger, Ulrich; Kuntze, Holger; Mayer-Steinacker, Regine; Moskopp, Dag; Schneider, Thomas; Beringer, Andreas; Schlegel, Uwe; Stummer, Walter; Welker, Helmut; Weyerbrock, Astrid; Paulsen, Frank; Rutkowski, Stefan; Weller, Michael; Wick, Wolfgang; Kortmann, Rolf-Dieter; Bogdahn, Ulrich; Hau, Peter

2018-02-19

Medulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy. The NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy. Thirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock. Radio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Anti-malarial activity and toxicity assessment of Himatanthus articulatus, a plant used to treat malaria in the Brazilian Amazon.

PubMed

Vale, Valdicley V; Vilhena, Thyago C; Trindade, Rafaela C Santos; Ferreira, Márlia Regina C; Percário, Sandro; Soares, Luciana F; Pereira, Washington Luiz A; Brandão, Geraldo C; Oliveira, Alaíde B; Dolabela, Maria F; De Vasconcelos, Flávio

2015-03-27

Plasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus. Ethanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulatus and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity--TEAC; lipid peroxidation--TBARS, and nitrites and nitrates--NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice. Plumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies. The ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.

Antitumor activity of monomethoxy poly(ethylene glycol)-poly (ε-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma.

PubMed

Zheng, Lan; Gou, Maling; Zhou, Shengtao; Yi, Tao; Zhong, Qian; Li, Zhengyu; He, Xiang; Chen, Xiancheng; Zhou, Lina; Wei, Yuquan; Qian, Zhiyong; Zhao, Xia

2011-06-01

Doxorubicin (Dox) is one of the most commonly used and highly effective antineoplastic agents, but the clinical application of this broad spectrum drug is largely hampered by its poor stability and serious toxicity to normal tissues. Hence, it is essential to improve the therapeutic effect and decrease the systematic toxicity for the administration of doxorubicin. In our study, doxorubicin was incorporated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelle by a self-assembly method. The cytotoxicity and cellular uptake efficiency of Dox-loaded MPEG-PCL (Dox/MPEG-PCL) micelle against B16-F10 murine melanoma cells was examined by the methylthiazoltetrazolium (MTT) test and flow cytometry. The antitumor activity of Dox/MPEG-PCL was evaluated in C57BL/6 mice injected subcutaneously with B16-F10 cells. Toxicity was evaluated in tumor-free mice. Meanwhile, tumor proliferation, intratumoal angiogenesis and apoptotic cells were evaluated by PCNA, CD31 staining and TUNEL assay, respectively. Encapsulation of doxorubicin in MPEG-PCL micelle improved the cytotoxicity of doxorubicin and enhanced its cellular uptake on B16-F10 cell in vitro. Administration of Dox/MPEG-PCL micelle resulted in significant inhibition (75% maximum inhibition relative to controls) in the growth of B16-F10 tumor xenografts and prolonged the survival of the treated mice (P<0.05). These anti-tumor responses were associated with marked increase of tumor apoptosis and notable reduction of cell proliferation and intratumoral microvessel density (P<0.05). The system toxicity also decreased in the Dox/MPEG-PCL group compared with free doxorubicin group. Our data indicate that the encapsulation of doxorubicin in MPEG-PCL micelle improved the anti-tumor activity in vivo without conspicuous systemic toxic effects.

Dynamic development of the protein corona on silica nanoparticles: composition and role in toxicity

NASA Astrophysics Data System (ADS)

Mortensen, Ninell P.; Hurst, Gregory B.; Wang, Wei; Foster, Carmen M.; Nallathamby, Prakash D.; Retterer, Scott T.

2013-06-01

The formation and composition of the protein corona on silica (SiO2) nanoparticles (NP) with different surface chemistries was evaluated over time. Native SiO2, amine (-NH2) and carboxy (-COO-) modified NP were examined following incubation in mammalian growth media containing fetal bovine serum (FBS) for 1, 4, 24 and 48 hours. The protein corona transition from its early dynamic state to the later more stable corona was evaluated using mass spectrometry. The NP diameter was 22.4 +/- 2.2 nm measured by scanning transmission electron microscopy (STEM). Changes in hydrodynamic diameter and agglomeration kinetics were studied using dynamic light scattering (DLS). The initial surface chemistry of the NP played an important role in the development and final composition of the protein corona, impacting agglomeration kinetics and NP toxicity. Particle toxicity, indicated by changes in membrane integrity and mitochondrial activity, was measured by lactate dehydrogenase (LDH) release and tetrazolium reduction (MTT), respectively, in mouse alveolar macrophages (RAW264.7) and mouse lung epithelial cells (C10). SiO2-COO- NP had a slower agglomeration rate, formed smaller aggregates, and exhibited lower cytotoxicity compared to SiO2 and SiO2-NH2. Composition of the protein corona for each of the three NP was unique, indicating a strong dependence of corona development on NP surface chemistry. This work underscores the need to understand all aspects of NP toxicity, particularly the influence of agglomeration on effective dose and particle size. Furthermore, the interplay between materials and local biological environment is emphasized and highlights the need to conduct toxicity profiling under physiologically relevant conditions that provide an appropriate estimation of material modifications that occur during exposure in natural environments.The formation and composition of the protein corona on silica (SiO2) nanoparticles (NP) with different surface chemistries was evaluated over time. Native SiO2, amine (-NH2) and carboxy (-COO-) modified NP were examined following incubation in mammalian growth media containing fetal bovine serum (FBS) for 1, 4, 24 and 48 hours. The protein corona transition from its early dynamic state to the later more stable corona was evaluated using mass spectrometry. The NP diameter was 22.4 +/- 2.2 nm measured by scanning transmission electron microscopy (STEM). Changes in hydrodynamic diameter and agglomeration kinetics were studied using dynamic light scattering (DLS). The initial surface chemistry of the NP played an important role in the development and final composition of the protein corona, impacting agglomeration kinetics and NP toxicity. Particle toxicity, indicated by changes in membrane integrity and mitochondrial activity, was measured by lactate dehydrogenase (LDH) release and tetrazolium reduction (MTT), respectively, in mouse alveolar macrophages (RAW264.7) and mouse lung epithelial cells (C10). SiO2-COO- NP had a slower agglomeration rate, formed smaller aggregates, and exhibited lower cytotoxicity compared to SiO2 and SiO2-NH2. Composition of the protein corona for each of the three NP was unique, indicating a strong dependence of corona development on NP surface chemistry. This work underscores the need to understand all aspects of NP toxicity, particularly the influence of agglomeration on effective dose and particle size. Furthermore, the interplay between materials and local biological environment is emphasized and highlights the need to conduct toxicity profiling under physiologically relevant conditions that provide an appropriate estimation of material modifications that occur during exposure in natural environments. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr33280b

Oral treatment with herbal formula B401 alleviates penile toxicity in aging mice with manganism.

PubMed

Hsu, Chih-Hsiang; Lin, Ching-Lung; Wang, Sheue-Er; Sheu, Shuenn-Jyi; Chien, Chiang-Ting; Wu, Chung-Hsin

2015-01-01

The present study aims to elucidate the roles of nitric oxide synthase activity, oxidative stress, inflammation, and apoptosis in penile toxicity of aging mice associated with excess manganese (Mn) treatment and to investigate the effect of oral treatment with the herbal formula B401 in this respect. ICR strain mice were divided into two groups: the vehicle (sham group) and the B401 (50 mg/kg) group. The mice were orally treated for 5 days; then a high single dose of MnCl2 (100 mg/kg) was given by intraperitoneal injection to the mice. One day after MnCl2 treatment, corpora cavernosal tissues of both Mn-treated mice and their controls were simultaneously sampled to examine their immunohistochemical staining and Western blot analysis. Nitric oxide (NO) production, levels of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), expression levels of factors governing angiogenesis (vascular endothelial growth factor), oxidative stress (catalase, superoxide dismutase 2,4-hydroxynonenal), inflammation (tumor necrosis factor alpha), apoptosis (B-cell lymphoma 2 [Bcl-2], Bcl-2-associated X protein [Bax], cleaved poly(adenosine diphosphate-ribose) polymerase [c-PARP], cytochrome C, caspase-12, and caspase-3) were evaluated in penile corpus cavernosum of the mice. We found that penile toxicity in the mice was enhanced under excess Mn treatment through reduction of NOS activity and increase in oxidative stress, inflammation, and apoptosis in the penile cavernous tissue. Furthermore, the penile toxicity in mice with manganism was alleviated by oral B401 treatment through enhancement of both nitric oxide synthesis and angiogenesis, with simultaneous reduction of oxidative stress, inflammation, and apoptosis in penile corpus cavernosum. We suggest that the herbal formula B401 may serve as a potential dietotherapeutic supplement for penile toxicity or dysfunction in aging males.

Photosynthetic, antioxidative, molecular and ultrastructural responses of young cacao plants to Cd toxicity in the soil.

PubMed

Pereira de Araújo, Romária; Furtado de Almeida, Alex-Alan; Silva Pereira, Lidiane; Mangabeira, Pedro A O; Olimpio Souza, José; Pirovani, Carlos P; Ahnert, Dário; Baligar, Virupax C

2017-10-01

Cadmium (Cd) is a highly toxic metal for plants, even at low concentrations in the soil. The annual production of world cocoa beans is approximately 4 million tons. Most of these fermented and dried beans are used in the manufacture of chocolate. Recent work has shown that the concentration of Cd in these beans has exceeded the critical level (0.6mgkg -1 DM). The objective of this study was to evaluate the toxicity of Cd in young plants of CCN 51 cacao genotype grown in soil with different concentrations of Cd (0, 0.05 and 0.1gkg -1 soil) through photosynthetic, antioxidative, molecular and ultrastructural changes. The increase of Cd concentration in the soil altered mineral nutrient absorption by competition or synergism, changed photosynthetic activity caused by reduction in chloroplastidic pigment content and damage to the photosynthetic machinery evidenced by the Fv/Fm ratio and expression of the psbA gene and increased GPX activity in the root and SOD in leaves. Additionally, ultrastructural alterations in roots and leaves were also evidenced with the increase of the concentration of Cd in the soil, whose toxicity caused rupture of biomembranes in root and leaf cells, reduction of the number of starch grains in foliar cells, increase of plastoglobules in chloroplasts and presence of multivesiculated bodies in root cells. It was concluded, therefore, that soil Cd toxicity caused damage to the photosynthetic machinery, antioxidative metabolism, gene expression and irreversible damage to root cells ultrastructure of CCN 51 cocoa plants, whose damage intensity depended on the exposure time to the metal. Copyright © 2017. Published by Elsevier Inc.

Effect of gamma irradiation on mistletoe (Viscum album) lectin-mediated toxicity and immunomodulatory activity☆

PubMed Central

Sung, Nak-Yun; Byun, Eui-Baek; Song, Du-Sup; Jin, Yeung-Bae; Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Jung, Pil-Mun; Byun, Myung-Woo; Lee, Ju-Woon; Park, Sang-Hyun; Kim, Jae-Hun

2013-01-01

This study evaluated the effect of gamma irradiation on the reduction of the toxicity of mistletoe lectin using both in vitro and in vivo models. To extract the lectin from mistletoe, an (NH4)2SO4 precipitation method was employed and the precipitant purified using a Sepharose 4B column to obtain the pure lectin fraction. Purified lectin was then gamma-irradiated at doses of 0, 5, 10, 15, and 20 kGy, or heated at 100 °C for 30 min. Toxic effects of non-irradiated, irradiated, and heat-treated lectins were tested using hemagglutination assays, cytotoxicity assays, hepatotoxicity, and a mouse survival test and immunological response was tested using cytokine production activity. Hemagglutination of lectin was remarkably decreased (P < 0.05) by irradiation at doses exceeding 10 kGy and with heat treatment. However, lectin irradiated with 5 kGy maintained its hemagglutination activity. The cytotoxicity of lectin was decreased by irradiation at doses over 5 kGy and with heat treatment. In experiments using mouse model, glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels were decreased in the group treated with the 5 kGy irradiated and heat-treated lectins as compared to the intact lectin, and it was also shown that 5 kGy irradiated and heat-treated lectins did not cause damage in liver tissue or mortality. In the result of immunological response, tumor necrosis factor (TNF-α) and interleukin (IL-6) levels were significantly (P < 0.05) increased in the 5 kGy gamma-irradiated lectin treated group. These results indicate that 5 kGy irradiated lectin still maintained the immunological response with reduction of toxicity. Therefore, gamma-irradiation may be an effective method for reducing the toxicity of lectin maintaining the immune response. PMID:23847758

Recombinant heat shock protein 27 (HSP27/HSPB1) protects against cadmium-induced oxidative stress and toxicity in human cervical cancer cells.

PubMed

Alvarez-Olmedo, Daiana G; Biaggio, Veronica S; Koumbadinga, Geremy A; Gómez, Nidia N; Shi, Chunhua; Ciocca, Daniel R; Batulan, Zarah; Fanelli, Mariel A; O'Brien, Edward R

2017-05-01

Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)-a multifunctional protein chaperone-has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity. Here, we report that the harmful effects of Cd correlated with changes in oxidative stress markers: upregulation of reactive oxygen species, reduction in nitric oxide (NO) bioavailability, increment in lipid peroxidation, peroxynitrite (PN), and protein nitration; intracellular HSP27 was reduced. Treatments with Cd (100 μM) for 24 h or with the peroxynitrite donor, SIN-1, decreased HSP27 levels (~50%), suggesting that PN formation is responsible for the reduction of HSP27. Pre-treatments of the cells either with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (a pharmacological inhibitor of NO synthase) or with recombinant HSP27 (rHSP27) attenuated the disruption of the cellular metabolism induced by Cd, increasing in a 55 and 52%, respectively, the cell viability measured by CCK-8. Cd induced necrotic cell death pathways, although apoptosis was also activated; pre-treatment with L-NAME or rHSP27 mitigated cell death. Our findings show for the first time a direct relationship between Cd-induced toxicity and PN production and a role for rHSP27 as a potential therapeutic agent that may counteract Cd toxicity.

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study.

PubMed

Sparks, Jeffrey A; Barbhaiya, Medha; Karlson, Elizabeth W; Ritter, Susan Y; Raychaudhuri, Soumya; Corrigan, Cassandra C; Lu, Fengxin; Selhub, Jacob; Chasman, Daniel I; Paynter, Nina P; Ridker, Paul M; Solomon, Daniel H

2017-08-01

The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo-controlled trial of LDM in the secondary prevention of cardiovascular disease. We describe here the rationale and design of the CIRT-Adverse Events (CIRT-AE) ancillary study which aims to investigate adverse events within CIRT. CIRT will randomize up to 7000 participants with cardiovascular disease and no systemic rheumatic disease to either LDM (target dose: 15-20mg/week) or placebo for an average follow-up period of 3-5 years; subjects in both treatment arms receive folic acid 1mg daily for 6 days each week. The primary endpoints of CIRT include recurrent cardio vascular events, incident diabetes, and all-cause mortality, and the ancillary CIRT-AE study has been designed to adjudicate other clinically important adverse events including hepatic, gastrointestinal, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. Methotrexate polyglutamate levels and genome-wide single nucleotide polymorphisms will be examined for association with adverse events. CIRT-AE will comprehensively evaluate potential LDM toxicities among subjects with cardiovascular disease within the context of a large, ongoing, double-blind, placebo-controlled trial. This information may lead to a personalized approach to monitoring LDM in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment and toxicity reduction of textile dyeing wastewater using the electrocoagulation-electroflotation process.

PubMed

Kim, Han-Lae; Cho, Jong-Bok; Park, Yong-Jin; Cho, Il-Hyoung

2016-07-02

A pilot-scale study was conducted using the electrocoagulation-electroflotation (EC-EF) process to treat textile dyeing raw wastewater to evaluate treatment performance. The effects of some key factors, such as current density, hydraulic retention time (HRT), and removal of conductivity, total suspended solids (TSS), chemical oxygen demand (COD), and color were investigated. The operating variables were current density of 0-300 A m(-2), HRT of 0-30 min, and a coagulant (anionic polyacrylamide (A-PAM)) dosage of 0-30 mg L(-1). Daphnia magna was used to test acute toxicity in raw and treated wastewater. Under the operating conditions without added coagulant, maxima of 51%, 88%, 84%, and 99% of conductivity, TSS, COD, and color were removed, respectively, with a HRT of 30 min. The coagulant enhanced removal of all wastewater parameters. Removal maxima of 59%, 92%, 94%, and 98% for conductivity, TSS, COD, and color were observed, respectively, with an optimal dosage of 30 mg L(-1) and a shortened HRT of 20 min. The 48 h-LC50 D. magna test showed that the raw wastewater was highly toxic. However, the EC-EF process decreased toxicity of the treated samples significantly, and >70% toxicity reduction was achieved by the EC-EF process with the addition of 15-30 mg L(-1) coagulant, HRT of 20 min, and current density of 150-300 A m(-2). The pilot scale test (0.3 m(3 )h(-1)) shows that the EC-EF process with added coagulant effectively treated textile dyeing wastewater.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

PubMed

Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-11-01

This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

Development and Application of Computational/In Vitro Toxicological Methods for Chemical Hazard Risk Reduction of New Materials for Advanced Weapon Systems

NASA Technical Reports Server (NTRS)

Frazier, John M.; Mattie, D. R.; Hussain, Saber; Pachter, Ruth; Boatz, Jerry; Hawkins, T. W.

2000-01-01

The development of quantitative structure-activity relationship (QSAR) is essential for reducing the chemical hazards of new weapon systems. The current collaboration between HEST (toxicology research and testing), MLPJ (computational chemistry) and PRS (computational chemistry, new propellant synthesis) is focusing R&D efforts on basic research goals that will rapidly transition to useful products for propellant development. Computational methods are being investigated that will assist in forecasting cellular toxicological end-points. Models developed from these chemical structure-toxicity relationships are useful for the prediction of the toxicological endpoints of new related compounds. Research is focusing on the evaluation tools to be used for the discovery of such relationships and the development of models of the mechanisms of action. Combinations of computational chemistry techniques, in vitro toxicity methods, and statistical correlations, will be employed to develop and explore potential predictive relationships; results for series of molecular systems that demonstrate the viability of this approach are reported. A number of hydrazine salts have been synthesized for evaluation. Computational chemistry methods are being used to elucidate the mechanism of action of these salts. Toxicity endpoints such as viability (LDH) and changes in enzyme activity (glutahoione peroxidase and catalase) are being experimentally measured as indicators of cellular damage. Extrapolation from computational/in vitro studies to human toxicity, is the ultimate goal. The product of this program will be a predictive tool to assist in the development of new, less toxic propellants.

Phase II Evaluation of IPI-926, an Oral Hedgehog Inhibitor, in Patients with Myelofibrosis

PubMed Central

Sasaki, Koji; Gotlib, Jason R.; Mesa, Ruben A.; Newberry, Kate J.; Ravandi, Farhad; Cortes, Jorge E.; Kelly, Patrick; Kutok, Jeffery L.; Kantarjian, Hagop M.; Verstovsek, Srdan

2016-01-01

The clinical safety and efficacy of IPI-926 was evaluated in 14 patients with myelofibrosis in a phase II study. Patients received 160-mg IPI-926 orally in continuous 28-day cycles. The median treatment duration was 5.1 months, and all patients had discontinued treatment by 7.5 months. Nine patients discontinued due to lack of response as determined by the treating physician, two after developing acute leukemia and one due to disease progression/loss of response. Twelve patients had slight reductions in spleen size (less than 50% from baseline), but symptoms did not improve consistently. One patient achieved transfusion independence lasting 5 months. Reductions in GLI1 mRNA and protein levels, JAK2V617F allele burden, degree of fibrosis, or cytokine levels were observed in some patients, but were not significant when evaluated for the cohort. Low-grade gastrointestinal/liver abnormalities were the most common toxicities. The results did not support continued evaluation of IPI-926 as a monotherapy in myelofibrosis. PMID:25641433

A Comparison of Real-Time and Endpoint Cell Viability Assays for Improved Synthetic Lethal Drug Validation.

PubMed

Single, Andrew; Beetham, Henry; Telford, Bryony J; Guilford, Parry; Chen, Augustine

2015-12-01

Cell viability assays fulfill a central role in drug discovery studies. It is therefore important to understand the advantages and disadvantages of the wide variety of available assay methodologies. In this study, we compared the performance of three endpoint assays (resazurin reduction, CellTiter-Glo, and nuclei enumeration) and two real-time systems (IncuCyte and xCELLigence). Of the endpoint approaches, both the resazurin reduction and CellTiter-Glo assays showed higher cell viabilities when compared directly to stained nuclei counts. The IncuCyte and xCELLigence real-time systems were comparable, and both were particularly effective at tracking the effects of drug treatment on cell proliferation at sub-confluent growth. However, the real-time systems failed to evaluate contrasting cell densities between drug-treated and control-treated cells at full growth confluency. Here, we showed that using real-time systems in combination with endpoint assays alleviates the disadvantages posed by each approach alone, providing a more effective means to evaluate drug toxicity in monolayer cell cultures. Such approaches were shown to be effective in elucidating the toxicity of synthetic lethal drugs in an isogenic pair of MCF10A breast cell lines. © 2015 Society for Laboratory Automation and Screening.

An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin.

PubMed

Dyer, Paul D R; Kotha, Arun K; Gollings, Alex S; Shorter, Susan A; Shepherd, Thomas R; Pettit, Marie W; Alexander, Bruce D; Getti, Giulia T M; El-Daher, Samer; Baillie, Les; Richardson, Simon C W

2016-07-01

The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC(50) for RT was 0.08±0.004 ng/mL whereas the IC(50) for RT+100 μM eGCG was 3.02±0.572 ng/mL, indicating that eGCG mediated a significant (p<0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC(50) values were obtained for RT (0.54±0.024 ng/mL) and RT+100 μM eGCG (0.68±0.235 ng/mL) again using 100 μM eGCG and was significant (p=0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100 μg/mL (i.e. 178 and 223 μM respectively) of eGCG mediating a significant (p=0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4 ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10 ng/mL and 5 ng/mL of RT was used. The addition of 1000 μM and 100 μM eGCG mediated a significant (p=0.0015 and <0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1 μg eGCG. Further, eGCG (100 μM) was found to reduce the binding of RT B chain to lactose-conjugated Sepharose as well as significantly (p=0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Assessment of the disinfection capacity and eco-toxicological impact of atmospheric cold plasma for treatment of food industry effluents.

PubMed

Patange, Apurva; Boehm, Daniela; Giltrap, Michelle; Lu, Peng; Cullen, P J; Bourke, Paula

2018-08-01

Generation of wastewater is one of the main environmental sustainability issues across food sector industries. The constituents of food process effluents are often complex and require high energy and processing for regulatory compliance. Wastewater streams are the subject of microbiological and chemical criteria, and can have a significant eco-toxicological impact on the aquatic life. Thus, innovative treatment approaches are required to mitigate environmental impact in an energy efficient manner. Here, dielectric barrier discharge atmospheric cold plasma (ACP) was evaluated for control of key microbial indicators encountered in food industry effluent. This study also investigated the eco-toxicological impact of cold plasma treatment of the effluents using a range of aquatic bioassays. Continuous ACP treatment was applied to synthetic dairy and meat effluents. Microbial inactivation showed treatment time dependence with significant reduction in microbial populations within 120 s, and to undetectable levels after 300 s. Post treatment retention time emerged as critical control parameter which promoted ACP bacterial inactivation efficiency. Moreover, ACP treatment for 20 min achieved significant reduction (≥2 Log 10 ) in Bacillus megaterium endospores in wastewater effluent. Acute aquatic toxicity was assessed using two fish cell lines (PLHC-1 and RTG-2) and a crustacean model (Daphnia magna). Untreated effluents were toxic to the aquatic models, however, plasma treatment limited the toxic effects. Differing sensitivities were observed to ACP treated effluents across the different test bio-assays in the following order: PLHC-1 > RTG-2 ≥ D. magna; with greater sensitivity retained to plasma treated meat effluent than dairy effluent. The toxic effects were dependent on concentration and treatment time of the ACP treated effluent; with 30% cytotoxicity in D. magna and fish cells observed after 24 h of exposure to ACP treated effluent for concentrations up to 5%. The findings suggest the need to employ wider variety of aquatic organisms for better understanding and complete toxicity evaluation of long-term effects. The study demonstrates the potential to tailor ACP system parameters to control pertinent microbial targets (mono/poly-microbial, vegetative or spore form) found in complex and nutritious wastewater effluents whilst maintaining a safe eco-toxicity profile for aquatic species. Copyright © 2018 Elsevier B.V. All rights reserved.

Moving further upstream: from toxics reduction to the precautionary principle.

PubMed

Mayer, Brian; Brown, Phil; Linder, Meadow

2002-01-01

Early policies to reduce the amount of toxic waste in the environment focused on cleaning up downstream sources of pollution, such as toxic disposal sites. Public attention in the 1980s encouraged both industry and government to develop an alternative to this command-and-control approach. This article describes the emergence of that alternative-pollution prevention-and its application in Massachusetts through the 1989 Toxics Use Reduction Act. Pollution prevention focuses on the sources of pollution, both metaphorically and physically, more upstream than its predecessors. The success of the Toxics Use Reduction Act in Massachusetts helped create an opportunity where an alternative pollution prevention paradigm could develop. That paradigm, the precautionary principle, is popular among environment activists because it focuses further upstream than pollution prevention by calling attention to the role the social construction of risk plays in decisions regarding the use of hazardous substances. The authors examine the evolution of the precautionary principle through an investigation of three major pathways in its development and expansion. The article concludes with a discussion of the increased potential for protecting public health and the environment afforded by this new perspective.

Reduction of aflatoxin B1 to aflatoxicol: a comprehensive DFT study provides clues to its toxicity.

PubMed

Karabulut, Sedat; Paytakov, Guvanchmyrat; Leszczynski, Jerzy

2014-12-01

Aflatoxicol (AFL) is one of most the important metabolites of aflatoxin B1 (AFB1). AFL can be formed through enzymatic or synthetic reduction of AFB1. Various experimental and theoretical studies have been focused on the AFB1 due to its high toxicity and carcinogenicity. The selective reduction of AFB1 carbonyls, molecular structure of AFL and its effect on toxicity has been studied here by the density functional theory (DFT) method. Although the toxicity of AFL is 18 times lower than that of AFB1, it has been concluded that both molecular structures have similar potency to form an exo-epoxide (AFEP) analogue which can bind to DNA. Calculations revealed that only one of the three possible tautomers of AFL is stable, both in the gas phase and water. The electronic properties of aflatoxicol are calculated as similar to aflatoxin B1 and this may be an explanation of similar carcinogenicity and toxicity of these compounds, which has been proved by experimental results. © 2014 Society of Chemical Industry.

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

PubMed

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

2017-02-01

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

Adsorption of Cd, Cu and Zn from aqueous solutions onto ferronickel slag under different potentially toxic metal combination.

PubMed

Park, Jong-Hwan; Kim, Seong-Heon; Kang, Se-Won; Kang, Byung-Hwa; Cho, Ju-Sik; Heo, Jong-Soo; Delaune, Ronald D; Ok, Yong Sik; Seo, Dong-Cheol

2016-01-01

Adsorption characteristics of potentially toxic metals in single- and multi-metal forms onto ferronickel slag were evaluated. Competitive sorption of metals by ferronickel slag has never been reported previously. The maximum adsorption capacities of toxic metals on ferronickel were in the order of Cd (10.2 mg g(-1)) > Cu (8.4 mg g(-1)) > Zn (4.4 mg g(-1)) in the single-metal adsorption isotherm and Cu (6.1 mg g(-1)) > Cd (2.3 mg g(-1)) > Zn (0.3 mg g(-1)) in the multi-metal adsorption isotherm. In comparison with single-metal adsorption isotherm, the reduction rates of maximum toxic metal adsorption capacity in the multi-metal adsorption isotherm were in the following order of Zn (93%) > Cd (78%) > Cu (27%). The Freundlich isotherm provides a slightly better fit than the Langmuir isotherm equation using ferronickel slag for potentially toxic metal adsorption. Multi-metal adsorption behaviors differed from single-metal adsorption due to competition, based on data obtained from Freundlich and Langmuir adsorption models and three-dimensional simulation. Especially, Cd and Zn were easily exchanged and substituted by Cu during multi-metal adsorption. Further competitive adsorption studies are necessary in order to accurately estimate adsorption capacity of ferronickel slag for potentially toxic metals in natural environments.

Reduction of petroleum hydrocarbons and toxicity in refinery wastewater by bioremediation.

PubMed

Płaza, Grazyna A; Jangid, Kamlesh; Lukasik, Krystyna; Nałecz-Jawecki, Grzegorz; Berry, Christopher J; Brigmon, Robin L

2008-10-01

The aim of the study was to investigate petroleum waste remediation and toxicity reduction by five bacterial strains: Ralstonia picketti SRS (BP-20), Alcaligenes piechaudii SRS (CZOR L-1B), Bacillus subtilis (I'-1a), Bacillus sp. (T-1), and Bacillus sp. (T'-1), previously isolated from petroleum-contaminated soils. Petroleum hydrocarbons were significantly degraded (91%) by the mixed bacterial cultures in 30 days (reaching up to 29% in the first 72 h). Similarly, the toxicity of the biodegraded petroleum waste decreased 3-fold after 30 days. This work shows the influence of bacteria on hydrocarbon degradation and associated toxicity, and its dependence on the specific microorganisms present. The ability of these mixed cultures to degrade hydrocarbons and reduce toxicity makes them candidates for environmental restoration applications at other hydrocarbon-contaminated environments.

The anthelmintic effect of aqueous methanol extract of Combretum molle (R. Br. x. G. Don) (Combretaceae) in lambs experimentally infected with Haemonchus contortus.

PubMed

Simon, M K; Ajanusi, O J; Abubakar, M S; Idris, A L; Suleiman, M M

2012-06-08

The aqueous methanol extract from the stem-bark of Combretum molle was evaluated for anthelmintic activity in lambs infected with Haemonchus contortus using faecal egg count (FEC) reduction assay. The extract showed a dose-dependent reduction in FEC in infected animals. At doses of 500, 1000 and 2000 mg kg(-1), the extract caused FEC reduction of 63%, 69.25% and 96.23%, respectively. Similarly, the standard anthelmintic (albendazole) at a dose of 200 mg kg(-1) produced FEC reduction of 99.24%. FEC reduction produced by the extract at doses of 500 and 1000 mg kg(-1) is below the minimum standard of 90% FEC recommended by the World Association for the Advancement of Veterinary Parasitology (WAAVP). However, there was no significant (P>0.05) difference between the means of groups treated with 1000 mg kg(-1) and 2000 mg kg(-1) compared to that of albendazole. In this study, C. molle has shown a promising anthelmintic activity against experimental haemonchosis. Nonetheless, further studies to evaluate its detailed toxicity are required for the plant extract to be developed into a useful anthelmintic drug. There is also the need to evaluate other parts of the plant (root, leaves, fruits, etc.) for the same effect. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparative effects of chlorpyrifos in wild type and cannabinoid Cb1 receptor knockout mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baireddy, Praveena; Liu, Jing; Hinsdale, Myron

2011-11-15

Endocannabinoids (eCBs) modulate neurotransmission by inhibiting the release of a variety of neurotransmitters. The cannabinoid receptor agonist WIN 55.212-2 (WIN) can modulate organophosphorus (OP) anticholinesterase toxicity in rats, presumably by inhibiting acetylcholine (ACh) release. Some OP anticholinesterases also inhibit eCB-degrading enzymes. We studied the effects of the OP insecticide chlorpyrifos (CPF) on cholinergic signs of toxicity, cholinesterase activity and ACh release in tissues from wild type (+/+) and cannabinoid CB1 receptor knockout (-/-) mice. Mice of both genotypes (n = 5-6/treatment group) were challenged with CPF (300 mg/kg, 2 ml/kg in peanut oil, sc) and evaluated for functional and neurochemicalmore » changes. Both genotypes exhibited similar cholinergic signs and cholinesterase inhibition (82-95% at 48 h after dosing) in cortex, cerebellum and heart. WIN reduced depolarization-induced ACh release in vitro in hippocampal slices from wild type mice, but had no effect in hippocampal slices from knockouts or in striatal slices from either genotype. Chlorpyrifos oxon (CPO, 100 {mu}M) reduced release in hippocampal slices from both genotypes in vitro, but with a greater reduction in tissues from wild types (21% vs 12%). CPO had no significant in vitro effect on ACh release in striatum. CPF reduced ACh release in hippocampus from both genotypes ex vivo, but reduction was again significantly greater in tissues from wild types (52% vs 36%). In striatum, CPF led to a similar reduction (20-23%) in tissues from both genotypes. Thus, while CB1 deletion in mice had little influence on the expression of acute toxicity following CPF, CPF- or CPO-induced changes in ACh release appeared sensitive to modulation by CB1-mediated eCB signaling in a brain-regional manner. -- Highlights: Black-Right-Pointing-Pointer C57Bl/6 mice showed dose-related cholinergic toxicity following subcutaneous chlorpyrifos exposure. Black-Right-Pointing-Pointer Wild type and cannabinoid CB1 receptor knockout littermates responded similarly to the toxic effects of chlorpyrifos. Black-Right-Pointing-Pointer OP-induced changes in acetylcholine release appeared sensitive to modulation by CB1-mediated endocannabinoid signaling.« less

ProTox: a web server for the in silico prediction of rodent oral toxicity.

PubMed

Drwal, Malgorzata N; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R; Preissner, Robert

2014-07-01

Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein-ligand-based pharmacophore models ('toxicophores') for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Reduction of Cr(VI) to Cr(III) in Artificially-Contaminated Soil using Chemical Reagents

NASA Astrophysics Data System (ADS)

Kostarelos, Konstantinos; Rao, Ennio; Reale, Daniela

2010-05-01

The presence of hexavalent chromium (CrVI) in soil is an environmental concern due to its effect on human health. The concern arises from the leaching and the seepage of Cr(VI) from soil to groundwater. A remediation approach that has been studied in the literature is that of reducing the hexavalent chromium to its trivalent form using a chemical reagent, namely ferrous sulfate heptahydrate (FeSO4.7H20). In this study, we compared performance of ferrous sulfate heptahydrate to sodium thiosulfate (Na2S2O3), a less costly reductant. The means of measuring the performance of the reductants is the US EPA's Toxicity Characteristic Leaching Procedure (TCLP), which states that the total chromium release from the soil must be less than 5 ppm. Because this treatment approach is pH sensitive and thus, susceptible to acid rain effects, it was studied with the intention that it be coupled with a stabilization/fixation approach so as to provide a second level of treatment; i.e., it is not intended to be the stand-alone treatment approach. In this study, the reductants were initially used to treat a contaminated, artificial soil and allowed to cure for varying time periods to determine the minimum curing time. Contaminated artificial soil were then prepared using the same percentage of white sand, kaolinite clay and potassium chromate and varying amount of water as a function of the humidity of the specimens in order to illucidate the effect of moisture on the reductant performance. Finally, the reductant (either ferrous sulfate heptahydrate or sodium thiosulfate) was added in varying doses to determine the best ratio Cr/reagent dose. Chromium release from the soil was evaluated with a modified Toxicity Characteristic Leaching Procedure (TCLP) test after allowing the samples to cure. Results indicated that chromium(VI) released from the specimens was less than 5 ppm for the samples treated with either ferrous sulfate heptahydrate (99.9% of reduction) and sodium thiosulfate (98.7% of reduction) with ratio Cr/reagent equal to 18.7 in both cases. In addition, samples treated with ferrous sulfate also exhibited a binding effect. In summary, reduction to a lower valence state can be an effective treatment option when coupled with a stabilization/solidification treatment, so that any chromium subsequently leached from the treated soil into groundwater is the less toxic and less mobile trivalent form of chromium. An alternative to ferrous sulfate heptahydrate, the less-expensive sodium thiosulfate, performed well as a reductant and is suggested for further study.

Olive oil mill wastewaters before and after treatment: a critical review from the ecotoxicological point of view.

PubMed

Justino, Celine I L; Pereira, Ruth; Freitas, Ana C; Rocha-Santos, Teresa A P; Panteleitchouk, Teresa S L; Duarte, Armando C

2012-03-01

The olive oil mill wastewater (OMW) is a problematic and polluting effluent which may degrade the soil and water quality, with critical negative impacts on ecosystems functions and services provided. The main purpose of this review paper is presenting the state of the art of OMW treatments focusing on their efficiency to reduce OMW toxicity, and emphasizing the role of ecotoxicological tests on the evaluation of such efficiency before the up-scale of treatment methodologies being considered. In the majority of research works, the reduction of OMW toxicity is related to the degradation of phenolic compounds (considered as the main responsible for the toxic effects of OMW on seed germination, on bacteria, and on different species of soil and aquatic invertebrates) or the decrease of chemical oxygen demand content, which is not scientifically sound. Batteries of ecotoxicological tests are not applied before and after OMW treatments as they should be, thus leading to knowledge gaps in terms of accurate and real assessment of OMW toxicity. Although the toxicity of OMW is usually high, the evaluation of effects on sub-lethal endpoints, on individual and multispecies test systems, are currently lacking, and the real impacts yielded by its dilution, in freshwater trophic chains of receiving systems can not be assessed. As far as the terrestrial compartment is considered, ecotoxicological data available include tests only with plants and the evaluation of soil microbial parameters, reflecting concerns with the impacts on crops when using OMW for irrigation purposes. The evaluation of its ecotoxicity to other edaphic species were not performed giving rise to a completely lack of knowledge about the consequences of such practice on other soil functions. OMW production is a great environmental problem in Mediterranean countries; hence, engineers, chemists and ecotoxicologists should face this problem together to find an ecologically friend solution.

Efficacy of novel acridine derivatives in the inhibition of hPrP90-231 prion protein fragment toxicity.

PubMed

Villa, Valentina; Tonelli, Michele; Thellung, Stefano; Corsaro, Alessandro; Tasso, Bruno; Novelli, Federica; Canu, Caterina; Pino, Albiana; Chiovitti, Katia; Paludi, Domenico; Russo, Claudio; Sparatore, Anna; Aceto, Antonio; Boido, Vito; Sparatore, Fabio; Florio, Tullio

2011-05-01

Quinacrine is one of the few molecules tested to treat patients affected by prion diseases, although the clinical outcome is largely unsatisfactory. To identify novel derivatives with higher neuroprotective activity, we evaluated the effects of a small library of acridine derivatives. The 6-chloro-2-methoxyacridine derivatives bearing on position 9 a quinolizidin-1-ylamino (Q1, Q2) or a quinolizidin-1-ylalkylamino residue (Q3, Q4, Q6, Q7), the thio-bioisoster of Q3 (Q5), the 9-(N-lupinylthiopropyl)amino derivative (Q8) and simple acridines (Q9 and Q10) were considered. We compared the effects of quinacrine and these novel analogues in the inhibition of the cytotoxic activity and protease K (PK) resistance of the human prion protein fragment 90-231 (hPrP90-231). We demonstrate that quinacrine caused a significant reduction of hPrP90-231 toxicity due to its binding to the fragment and the prevention of its conversion in a toxic isoform. All acridine derivatives analyzed showed high affinity binding for hPrP90-231, but only Q3 and Q10, caused a significant reduction of hPrP90-231 cytotoxicity, with higher efficacy than quinacrine. We attempted to correlate the cytoprotective effects of the new compounds with some biochemical parameters (binding affinity to hPrP90-231, intrinsic fluorescence quenching, hydrophobic amino acid exposure), but a direct relationship occurred only with the reduction of PK resistance, likely due to the prevention of the acquisition of the β-sheet-rich toxic conformation. These data represent interesting leads for further modifications of the basic side chain and the substituent pattern of the acridine nucleus to develop novel compounds with improved antiprion activity to be tested in in vivo experimental setting.

Antibacterial, modulatory activity of antibiotics and toxicity from Rhinella jimi (Stevaux, 2002) (Anura: Bufonidae) glandular secretions.

PubMed

Sales, Débora Lima; Morais-Braga, Maria Flaviana Bezerra; Santos, Antonia Thassya Lucas Dos; Machado, Antonio Judson Targino; Araujo Filho, João Antonio de; Dias, Diógenes de Queiroz; Cunha, Francisco Assis Bezerra da; Saraiva, Rogério de Aquino; Menezes, Irwin Rose Alencar de; Coutinho, Henrique Douglas Melo; Costa, José Galberto Martins; Ferreira, Felipe Silva; Alves, Rômulo Romeu da Nóbrega; Almeida, Waltécio de Oliveira

2017-08-01

The increase in microorganisms with resistance to medications has caused a strong preoccupation within the medical and scientific community. Animal toxins studies, such as parotoid glandular secretions from amphibians, possesses a great potential in the development of drugs, such as antimicrobials, as these possess bioactive compounds. It was evaluated Rhinella jimi (Stevaux, 2002) glandular secretions against standard and multi-resistant bacterial strains; the effect of secretions combined with drugs; and determined the toxicity using two biologic in vivo models, and a in vitro model with mice livers. Standard strains were used for the determination of the Minimum Inhibitory Concentration (MIC), while for the modulatory activity of antibiotics, the clinical isolates Escherichia coli 06, Pseudomonas aeruginosa 03 and Staphylococcus aureus 10 were used. Modulatory activity was evaluated by the broth microdilution method with aminoglycosides and β-lactams as target antibiotics. The secretions in association with the antibiotics have a significant reduction in MIC, both the aminoglycosides and β-lactams. The toxicity and cytotoxicity results were lower than the values used in the modulation. R. jimi glandular secretions demonstrated clinically relevant results regarding the modulation of the tested antimicrobials. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Biochemical Changes after Short-term Oral Exposure of Jatropha curcas Seeds in Wistar Rats

PubMed Central

Awasthy, Vijeyta; Vadlamudi, V. P.; Koley, K. M.; Awasthy, B. K.; Singh, P. K.

2010-01-01

Jatropha curcas (Euphorbiaceae) is a multipurpose shrub with varied medicinal uses and is of significant economic importance. In addition to being the source of biodiesel, its seeds are also considered highly nutritious and could be exploited as a rich and economical protein supplement in animal feeds. However, the inherent phytotoxins present in the seed is the hindrance. The toxicity nature of the seeds of the local variety of J. curcas is not known. Therefore, investigations were undertaken to evaluate the short-term oral toxicity of the seeds of locally grown J. curcas. Short-term toxicity was conducted in rats by daily feeding the basal diet (Group I), and the diet in which the crude protein requirement was supplemented at 25% (Group II) and 50% (Group III) levels through Jatropha seed powder. The adverse effects of Jatropha seed protein supplementation (JSPS) were evaluated by observing alterations in biochemical profiles. The biochemical profile of rats fed on diet with JSPS at both the levels revealed significant reduction in plasma glucose and total protein and increase in plasma creatinine, transaminases (Plasma glutamic pyruvic transaminase and Plasma glutamic oxaloacetic transaminase), and alkaline phosphatase. PMID:21170248

Effect of Probiotic Bacillus Coagulans and Lactobacillus Plantarum on Alleviation of Mercury Toxicity in Rat.

PubMed

Majlesi, Majid; Shekarforoush, Seyed Shahram; Ghaisari, Hamid Reza; Nazifi, Saeid; Sajedianfard, Javad; Eskandari, Mohammad Hadi

2017-09-01

The objective of this study was to evaluate the efficiency of probiotics (Lactobacillus plantarum and Bacillus coagulans) against mercury-induced toxicity using a rat model. Mercury (Hg) is a widespread heavy metal and was shown to be associated with various diseases. Forty-eight adult male Wistar rats were randomly divided into six groups (control, mercury-only, each probiotic-only, and mercury plus each probiotic group). Hg-treated groups received 10 ppm mercuric chloride, and probiotic groups were administrated 1 × 10 9  CFU of probiotics daily for 48 days. Levels of mercury were determined using cold vapor technique, and some biochemical factors (list like glutathione peroxidase (GPx), superoxide dismutase (SOD), creatinine, urea, bilirubin, alanine transaminase (ALT), and aspartate transaminase (AST)) were measured to evaluate changes in oxidative stress. Oral administration of either probiotic was found to provide significant protection against mercury toxicity by decreasing the mercury level in the liver and kidney and preventing alterations in the levels of GPx and SOD. Probiotic treatment generated marked reduction in the levels of creatinine, urea, bilirubin, ALT, and AST indicating the positive influence of the probiotics on the adverse effects of Hg in the body.

Conceptual Chemical Process Design for Sustainability. ...

EPA Pesticide Factsheets

This chapter examines the sustainable design of chemical processes, with a focus on conceptual design, hierarchical and short-cut methods, and analyses of process sustainability for alternatives. The chapter describes a methodology for incorporating process sustainability analyses throughout the conceptual design. Hierarchical and short-cut decision-making methods will be used to approach sustainability. An example showing a sustainability-based evaluation of chlor-alkali production processes is presented with economic analysis and five pollutants described as emissions. These emissions are analyzed according to their human toxicity potential by ingestion using the Waste Reduction Algorithm and a method based on US Environmental Protection Agency reference doses, with the addition of biodegradation for suitable components. Among the emissions, mercury as an element will not biodegrade, and results show the importance of this pollutant to the potential toxicity results and therefore the sustainability of the process design. The dominance of mercury in determining the long-term toxicity results when energy use is included suggests that all process system evaluations should (re)consider the role of mercury and other non-/slow-degrading pollutants in sustainability analyses. The cycling of nondegrading pollutants through the biosphere suggests the need for a complete analysis based on the economic, environmental, and social aspects of sustainability. Chapter reviews

Chinese Herbal Medicine and Fluorouracil-Based Chemotherapy for Colorectal Cancer

PubMed Central

McCulloch, Michael; Ly, Helen; Broffman, Michael; See, Caylie; Clemons, Jen; Chang, Raymond

2016-01-01

Background. Chinese herbal medicines reportedly increase efficacy and minimize toxicity of chemotherapy; however, little attention has been paid to how poor study quality can bias outcomes. Methods. We systematically searched MEDLINE, TCMLARS, EMBASE, and Cochrane Library for randomized controlled trials of Chinese herbal medicines combined with fluorouracil-based chemotherapy compared with the same chemotherapy alone. We screened for eligibility, extracted data, and pooled data with random-effects meta-analysis. Outcome measures were survival, toxicity, tumor response, performance status, quality of life, and Cochrane Risk of Bias (ROB) criteria to critically evaluate the quality of reporting in the randomized trials included in the meta-analysis. Results. We found 36 potentially eligible studies, with only 3 (those with low ROB) qualifying for meta-analysis. Two reported chemotherapy-related diarrhea reduced by 57% (relative risk [RR] = 0.43; 95% CI = 0.19-1.01; I2 test for variation in RR due to heterogeneity = 0.0%), with nonsignificant results. Two reported white blood cell toxicity reduced by 66% (RR = 0.34; 95% CI = 0.16-0.72; I2 test for variation in RR due to heterogeneity = 0.0%), with statistically significant results. Stratifying analysis by studies with high versus low ROB, we found substantial overestimation of benefit: Studies with high ROB overestimated by nearly 2-fold reduction of platelet toxicity by Chinese herbal medicines (RR = 0.35, 95% CI = 0.15-0.84 vs RR = 0.65, 95% CI = 0.11-3.92). Studies with high ROB overestimated by nearly 2-fold reduction of vomiting toxicity (RR = 0.45, 95% CI = 0.33-0.61 vs RR = 0.87, 95% CI = 0.48-1.58). And, studies with high ROB overestimated by 21% the reduction in diarrhea toxicity (RR = 0.34, 95% CI = 0.20-0.58 vs RR = 0.43, 95% CI = 0.19-1.01). Studies with high ROB also overestimated by 16% improvement in tumor response (RR = 1.39, 95% CI = 1.18-1.63 vs RR = 1.20; 95% CI = 0.81-1.79). Not accounting for ROB would have exaggerated evidence of benefit and failed to detect nonsignificance of results. Conclusions. In the present analysis, involving 36 studies, 2593 patients, 20 outcomes, 36 medical institutions, and 271 named research authors, 92% of the data points were from studies at high ROB. Given the poor quality of the data in studies identified, it cannot be concluded whether combining Chinese herbs with chemotherapy reduces toxicity of chemotherapy. PMID:27151587

Molecular impact of juvenile hormone agonists on neonatal Daphnia magna.

PubMed

Toyota, Kenji; Kato, Yasuhiko; Miyakawa, Hitoshi; Yatsu, Ryohei; Mizutani, Takeshi; Ogino, Yukiko; Miyagawa, Shinichi; Watanabe, Hajime; Nishide, Hiroyo; Uchiyama, Ikuo; Tatarazako, Norihisa; Iguchi, Taisen

2014-05-01

Daphnia magna has been used extensively to evaluate organism- and population-level responses to pollutants in acute toxicity and reproductive toxicity tests. We have previously reported that exposure to juvenile hormone (JH) agonists results in a reduction of reproductive function and production of male offspring in a cyclic parthenogenesis, D. magna. Recent advances in molecular techniques have provided tools to understand better the responses to pollutants in aquatic organisms, including D. magna. DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to JH agonists: methoprene (125, 250 and 500 ppb), fenoxycarb (0.5, 1 and 2 ppb) and epofenonane (50, 100 and 200 ppb). Exposure to these JH analogs resulted in chemical-specific patterns of gene expression. The heat map analyses based on hierarchical clustering revealed a similar pattern between treatments with a high dose of methoprene and with epofenonane. In contrast, treatment with low to middle doses of methoprene resulted in similar profiles to fenoxycarb treatments. Hemoglobin and JH epoxide hydrolase genes were clustered as JH-responsive genes. These data suggest that fenoxycarb has high activity as a JH agonist, methoprene shows high toxicity and epofenonane works through a different mechanism compared with other JH analogs, agreeing with data of previously reported toxicity tests. In conclusion, D. magna DNA microarray is useful for the classification of JH analogs and identification of JH-responsive genes. Copyright © 2013 John Wiley & Sons, Ltd.

Treatment modifications in tumour necrosis factor-α (TNF)-based isolated limb perfusion in patients with advanced extremity soft tissue sarcomas.

PubMed

Deroose, Jan P; Grünhagen, Dirk J; de Wilt, Johannes H W; Eggermont, Alexander M M; Verhoef, Cornelis

2015-02-01

Tumour necrosis factor-α (TNF) and melphalan based isolated limb perfusion (TM-ILP) is an attractive treatment option for advanced extremity soft tissue sarcomas (STS). This study reports on a 20-year single centre experience and discusses the evolution and changes in methodology since the introduction of TNF in ILP. We performed 306 TM-ILPs in 275 patients with extremity STS. All patients were candidates for amputation or mutilating surgery in order to achieve local control. Clinical response evaluation consisted of clinical examination and magnetic resonance imaging. To evaluate the importance of TNF-dose, treatment results of two periods (1991-2003 high dose (3-4 mg) TNF; 2003-2012 reduced dose (1-2mg) TNF) were compared. During the study period, more femoral perfusions were done instead of iliac perfusions. Reduction of TNF dose and reduction of total ILP time did not lead to different clinical response rates (70% and 69% for periods 1 and 2 respectively) or different local recurrence rates, but was associated with less local toxicity (23% and 14% for periods 1 and 2 respectively). Hospital stay was significantly reduced during the study period. There was an improved pathological response in the high dose TNF group without consequences for clinical outcome. TM-ILP remains a very effective treatment modality for limb threatening extremity STS. Moreover, reduction of dose and the growing experience in ILP led to less local toxicity and shorter hospital stay. Copyright © 2014 Elsevier Ltd. All rights reserved.

Food avoidance behavior to dietary octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) exposure in the northern bobwhite (Colinusvirginianus).

PubMed

Johnson, Mark S; Gogal, Robert M; Larsen, Calvert T

2005-08-13

High-melting explosive (HMX; octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) is a widely utilized explosive component of munitions used by the military. Consequently, production and use through testing and training at military installations has resulted in deposition of HMX in soil. Since these areas are often used by birds, the oral toxicity of HMX exposure to northern bobwhite (Colinus virginianus) was evaluated. Attempts to determine the acute lethal dose were unsuccessful. Initially, 8 birds (1 male/1 female per dose group) were orally dosed at levels ranging from 125 to 2125 mg HMX/kg body weight. A single death at the midrange resulted in subsequent trials of oral doses up to 10,760 mg/kg body weight. Only a single death occurred at 7173 mg/kg. A subsequent 28-d feeding study was then conducted to evaluate the potential for toxicity resulting from repetitive oral exposures. Northern bobwhite were exposed to concentrations of HMX in feed of either 10000, 1000, 100, or 0 mg/kg. These exposures resulted in a clear concentration-related reduction in feed consumption and body mass. Reductions in egg production in females were correlated with changes in body mass and feed consumption. Other physiological indicators were consistent with a considerable reduction in feed intake. These results suggest that HMX concentration is responsible for intense feed aversion behavior and thus not likely a factor that would appreciably contribute to risk for wild birds at military ranges.

Propulsion Risk Reduction Activities for Non-Toxic Cryogenic Propulsion

NASA Technical Reports Server (NTRS)

Smith, Timothy D.; Klem, Mark D.; Fisher, Kenneth

2010-01-01

The Propulsion and Cryogenics Advanced Development (PCAD) Project s primary objective is to develop propulsion system technologies for non-toxic or "green" propellants. The PCAD project focuses on the development of non-toxic propulsion technologies needed to provide necessary data and relevant experience to support informed decisions on implementation of non-toxic propellants for space missions. Implementation of non-toxic propellants in high performance propulsion systems offers NASA an opportunity to consider other options than current hypergolic propellants. The PCAD Project is emphasizing technology efforts in reaction control system (RCS) thruster designs, ascent main engines (AME), and descent main engines (DME). PCAD has a series of tasks and contracts to conduct risk reduction and/or retirement activities to demonstrate that non-toxic cryogenic propellants can be a feasible option for space missions. Work has focused on 1) reducing the risk of liquid oxygen/liquid methane ignition, demonstrating the key enabling technologies, and validating performance levels for reaction control engines for use on descent and ascent stages; 2) demonstrating the key enabling technologies and validating performance levels for liquid oxygen/liquid methane ascent engines; and 3) demonstrating the key enabling technologies and validating performance levels for deep throttling liquid oxygen/liquid hydrogen descent engines. The progress of these risk reduction and/or retirement activities will be presented.

ENCOURAGING TOXIC USE REDUCTION IN ACADEMIC LABORATORIES

EPA Science Inventory

This project seeks to balance essential research with its associated environmental burdens by promoting the use of less toxic and less polluting alternatives to commonly used toxic chemicals. MIT seeks to use the purchasing process to provide researchers with the o...

Factors affecting the toxicity of trace metals to fertilization success in broadcast spawning marine invertebrates: A review.

PubMed

Hudspith, M; Reichelt-Brushett, Amanda; Harrison, Peter L

2017-03-01

Significant amounts of trace metals have been released into both nearshore and deep sea environments in recent years, resulting in increased concentrations that can be toxic to marine organisms. Trace metals can negatively affect external fertilization processes in marine broadcast spawners and may cause a reduction in fertilization success at elevated concentrations. Due to its sensitivity and ecological importance, fertilization success has been widely used as a toxicity endpoint in ecotoxicological testing, which is an important method of evaluating the toxicity of contaminants for management planning. Ecotoxicological data regarding fertilization success are available across the major marine phyla, but there remain uncertainties that impair our ability to confidently interpret and analyse these data. At present, the cellular and biochemical events underlying trace metal toxicity in external fertilization are not known. Metal behavior and speciation play an important role in bioavailability and toxicity but are often overlooked, and disparities in experimental designs between studies limit the degree to which results can be synthesised and compared to those of other relevant species. We reviewed all available literature covering cellular toxicity mechanisms, metal toxicities and speciation, and differences in methodologies between studies. We conclude that the concept of metal toxicity should be approached in a more holistic manner that involves elucidating toxicity mechanisms, improving the understanding of metal behavior and speciation on bioavailability and toxicity, and standardizing the fertilization assay methods among different groups of organisms. We identify opportunities to improve the fertilization assay that will allow robust critical and comparative analysis between species and their sensitivities to trace metals during external fertilization, and enable data to be more readily extrapolated to field conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Climate change air toxic co-reduction in the context of macroeconomic modelling.

PubMed

Crawford-Brown, Douglas; Chen, Pi-Cheng; Shi, Hsiu-Ching; Chao, Chia-Wei

2013-08-15

This paper examines the health implications of global PM reduction accompanying greenhouse gas emissions reductions in the 180 national economies of the global macroeconomy. A human health effects module based on empirical data on GHG emissions, PM emissions, background PM concentrations, source apportionment and human health risk coefficients is used to estimate reductions in morbidity and mortality from PM exposures globally as co-reduction of GHG reductions. These results are compared against the "fuzzy bright line" that often underlies regulatory decisions for environmental toxics, and demonstrate that the risk reduction through PM reduction would usually be considered justified in traditional risk-based decisions for environmental toxics. It is shown that this risk reduction can be on the order of more than 4 × 10(-3) excess lifetime mortality risk, with global annual cost savings of slightly more than $10B, when uniform GHG reduction measures across all sectors of the economy form the basis for climate policy ($2.2B if only Annex I nations reduce). Consideration of co-reduction of PM-10 within a climate policy framework harmonized with other environmental policies can therefore be an effective driver of climate policy. An error analysis comparing results of the current model against those of significantly more spatially resolved models at city and national scales indicates errors caused by the low spatial resolution of the global model used here may be on the order of a factor of 2. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gamma Radiation Reduced Toxicity of Azoxystrobin Tested on Artemia franciscana.

PubMed

Dvorak, P; Zdarsky, M; Benova, K; Falis, M; Tomko, M

2016-06-01

Fungicide azoxystrobin toxicity was monitored by means of a 96-h biotest with Artemia franciscana nauplius stages after exposure to solutions with concentrations of 0.2, 0.4, 0.6 and 0.8 mg L(-1) irradiated with (60)Co gamma radiation with doses of 1, 2.5, 5 and 10 kGy. The effects of ionization radiation on azoxystrobin toxicity were mainly manifested by a statistically significant reduction of lethality after 72- and 96-h exposure. A maximum reduction of lethality of 72 % was achieved using doses of 1-5 kGy for an azoxystrobin initial concentration of 0.4 mg L(-1) and after 72 h of exposure. At a 96-h exposure, a difference of lethal effects reached up to 70 % for a dose of 10 kGy. The observed effect of gamma ionizing radiation on azoxystrobin toxicity suggest that this approach can be applied as an alternative for a reduction of azoxystrobin residua in food.

Protective effect of Selenium nanoparticle against cyclophosphamide induced hepatotoxicity and genotoxicity in Swiss albino mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Ghosh, Prosenjit; Biswas, Jaydip; Bhattacharya, Sudin

2014-08-01

Cyclophosphamide (CP) is the most commonly used chemotherapeutic drug for various types of cancer. However, its use causes severe cytotoxicity to normal cells in human. It is well known that the undesirable side effects are caused due to the formation of reactive oxygen species. Selenium is an essential micronutrient for both animals and humans and has antioxidant and membrane stabilizing property, but selenium is also toxic above certain level. Nano selenium has been well proved to be less toxic than inorganic selenium as well as certain organoselenium compounds. The objective of the study is to evaluate the protective role of Nano-Se against CP-induced hepatotoxicity and genotoxicity in Swiss albino mice. CP was administered intraperitoneally (25 mg/kg b.w.) and Nano-Se was given by oral gavages (2 mg Se/kg b.w.) in concomitant and pretreatment scheme. Intraperitoneal administration of CP induced hepatic damage as indicated by the serum marker enzymes aspartate and alanine transaminases and increased the malonaldehyde level, depleted the glutathione content and antioxidant enzyme activity (glutathione peroxidase, glutathione-s-transferase, superoxide dismutase and catalase), and induced DNA damage and chromosomal aberration. Oral administration of Nano-Se caused a significant reduction in malonaldehyde, ROS level and glutathione levels, restoration of antioxidant enzyme activity, reduction in chromosomal aberration in bone marrow, and DNA damage in lymphocytes and also in bone marrow. Moreover, the chemoprotective efficiency of Nano-Se against CP induced toxicity was confirmed by histopathological evaluation. The results support the protective effect of Nano-Se against CP-induced hepatotoxicity and genotoxicity. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Specific detection of membrane-toxic substances with a conductivity assay.

PubMed

Eich, J; Dürholt, H; Steger-Hartmann, T; Wagner, E

2000-03-01

A conductivity assay that represents a new biotest able to detect the effects of membrane-toxic compounds, e.g., detergents, organic solvents, and radical formers, on various organisms was previously described and developed. The conductivity assay measures ion leakage from cells, tissues, or whole plant and animal organisms whose membrane systems have been damaged by membrane-toxic compounds. In this study the specificity of the conductivity assay for membrane-toxic compounds was tested by comparing the electrolyte efflux from Elodea canadensis leaves during incubation with a well-known detergent (benzalkonium chloride) using different plant physiological and biochemical techniques (photochemical efficiency, plasmolysis capacity, NBT reduction, and electron microscopy of membranes of E. canadensis leaves). The comparison of the different methods proved that the electrolyte loss during benzalkonium chloride incubation determined in the conductivity assay is due to membrane impairment. The observed electrolyte loss correlated with a reduction of photochemical efficiency and a decrease in both plasmolysis and NBT reduction capacity. Furthermore, a disintegration of the plasmalemma could be seen in the electron micrographs. These results indicate that the measured electrolyte loss in the conductivity assay is a specific effect of membrane-toxic compounds. Copyright 2000 Academic Press.

Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients

PubMed Central

Jiao, Lijing; Dong, Changsheng; Liu, Jiaxiang; Chen, Zhiwei; Zhang, Lei; Xu, Jianfang; Shen, Xiaoyong; Che, Jiaming; Yang, Yi; Huang, Hai; Li, Hegen; Sun, Jianli; Jiang, Yi; Mao, Zhujun; Chen, Peiqi; Gong, Yabin; Jin, Xiaolin; Xu, Ling

2017-01-01

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens. PMID:28436479

Physiological selectivity and activity reduction of insecticides by rainfall to predatory wasps of Tuta absoluta.

PubMed

Barros, Emerson C; Bacci, Leandro; Picanco, Marcelo C; Martins, Júlio C; Rosado, Jander F; Silva, Gerson A

2015-01-01

In this study, we carried out three bioassays with nine used insecticides in tomato crops to identify their efficiency against tomato leaf miner Tuta absoluta, the physiological selectivity and the activity reduction of insecticides by three rain regimes to predatory wasps Protonectarina sylveirae and Polybia scutellaris. We assessed the mortality caused by the recommended doses of abamectin, beta-cyfluthrin, cartap, chlorfenapyr, etofenprox, methamidophos, permethrin, phenthoate and spinosad to T. absoluta and wasps at the moment of application. In addition, we evaluated the wasp mortality due to the insecticides for 30 days on plants that did not receive rain and on plants that received 4 or 125 mm of rain. Spinosad, cartap, chlorfenapyr, phenthoate, abamectin and methamidophos caused mortality higher than 90% to T. absoluta, whereas the pyrethroids beta-cyfluthrin, etofenprox and permethrin caused mortality between 8.5% and 46.25%. At the moment of application, all the insecticides were highly toxic to the wasps, causing mortality higher than 80%. In the absence of rain, all the insecticides continued to cause high mortality to the wasps for 30 days after the application. The toxicity of spinosad and methamidophos on both wasp species; beta-cyfluthrin on P. sylveirae and chlorfenapyr and abamectin on P. scutellaris, decreased when the plants received 4 mm of rain. In contrast, the other insecticides only showed reduced toxicity on the wasps when the plants received 125 mm of rain.

Modulatory effects of Zn2+ ions on the toxicity of citrate- and PVP-capped gold nanoparticles towards freshwater algae, Scenedesmus obliquus.

PubMed

Iswarya, V; Johnson, J B; Parashar, Abhinav; Pulimi, Mrudula; Chandrasekaran, N; Mukherjee, Amitava

2017-02-01

Gold nanoparticles (GNPs) are widely used for medical purposes, both in diagnostics as well as drug delivery, and hence are prone to release and distribution in the environment. Thus, we have explored the effects of GNPs with two distinct surface capping (citrate and PVP), and three different sizes (16, 27, and 37 nm) at 0.01-, 0.1-, and 1-mg L -1 concentrations on a predominant freshwater alga Scenedesmus obliquus in the sterile freshwater matrix. We have also investigated how an abundant metal ion from freshwater, i.e., Zn 2+ ions may modulate the effects of the selected GNPs (40 nm, citrate, and PVP capped). Preliminary toxicity results revealed that gold nanoparticles were highly toxic in comparison to zinc ions alone. A significant modulation in the toxicity of Zn ions was not noticed in the presence of GNPs. In contrast, zinc ions minimized the toxicity produced by GNPs (both CIT-37 and PVP-37), despite its individual toxicity. Approximately, about 42, 33, and 25% toxicity reduction was noted at 0.05-, 0.5-, and 5-mg L -1 Zn ions, respectively, for CIT-37 GNPs, while 31% (0.05 mg L -1 ), 24% (0.5 mg L -1 ), and 9% (5 mg L -1 ) of toxicity reduction were noted for PVP-37 GNPs. Maximum toxicity reduction was seen at 0.05 mg L -1 of Zn ions. Abbott modeling substantiated antagonistic effects offered by Zn 2+ ions on GNPs. Stability and sedimentation data revealed that the addition of zinc ions gradually induced the aggregation of NPs and in turn significantly reduced the toxicity of GNPs. Thus, the naturally existing ions like Zn 2+ have an ability to modulate the toxicity of GNPs in a real-world environment scenario.

Applications in environmental bioinorganic: Nutritional and ultrastructural evaluation and calculus of thermodynamic and structural properties of metal-oxalate complexes.

PubMed

Tolentino, Terezinha Alves; Bertoli, Alexandre Carvalho; dos Santos Pires, Maíra; Carvalho, Ruy; Labory, Claudia Regina Gontijo; Nunes, Janaira Santana; Bastos, Ana Rosa Ribeiro; de Freitas, Matheus Puggina

2015-01-01

Lead (Pb) is known by its toxicity both for animals and plants. In order to evaluate its toxicity, plants of Brachiaria brizantha were cultivated on nutritive solution of Hoagland during 90 days and submitted to different concentrations of Pb. The content of macro and micronutrients was evaluated and there was a reduction on root content of Ca, besides the lowest dosages of Pb had induced an increase of N, S, Mn, Cu, Zn and Fe. The cell ultrastructure of leaves and roots were analyzed by transmission electronic microscopy (TEM). Among the main alterations occurred there were invaginations on cell walls, the presence of crystals on the root cells, accumulation of material on the interior of cells and vacuolar compartmentalization. On the leaves the degradation of chloroplasts was observed, as well as the increase of vacuoles. Structures for the formation of oxalate crystals were proposed through molecular modeling and thermodynamic stability. Calculi suggest the formation of highly stable metal-oxalate complexes. Copyright © 2015 Elsevier B.V. All rights reserved.

Natural and induced reduction of hexavalent chromium in soil

NASA Astrophysics Data System (ADS)

Leita, Liviana; Margon, Alja; Sinicco, Tania; Mondini, Claudio; Valentini, Massimiliano; Cantone, Pierpaolo

2013-04-01

Even though naturally elevated levels of chromium can be found naturally in some soils, distressing amounts of the hexavalent form (CrVI) are largely restricted to sites contaminated by anthropogenic activities. In fact, the widespread use of chromium in various industries and the frequently associated inadequate disposal of its by-products and wastes have created serious environmental pollution problems in many parts of the world. CrVI is toxic to plants, animals and humans and exhibits also mutagenic effects. However, being a strong oxidant, CrVI can be readily reduced to the much less harmful trivalent form (CrIII) when suitable electron donors are present in the environment. CrIII is relatively insoluble, less available for biological uptake, and thus definitely less toxic for web-biota. Various electron donors in soil can be involved in CrVI reduction in soil. The efficiency of CrVI reducing abiotic agents such as ferrous iron and sulphur compounds is well documented. Furthermore, CrVI reduction is also known to be significantly enhanced by a wide variety of cell-produced monosaccharides, including glucose. In this study we evaluated the dynamics of hexavalent chromium (CrVI) reduction in contaminated soil amended or not with iron sulphate or/and glucose and assessed the effects of CrVI on native or glucose-induced soil microbial biomass size and activity. CrVI negatively affected both soil microbial activity and the size of the microbial biomass. During the incubation period, the concentration of CrVI in soil decreased over time whether iron sulphate or/and glucose was added or not, but with different reduction rates. Soil therefore displayed a natural attenuation capacity towards chromate reduction. Addition of iron sulphate or/and glucose, however, increased the reduction rate by both abiotic and biotic mechanisms. Our data suggest that glucose is likely to have exerted an indirect role in the increased rate of CrVI reduction by promoting growth of indigenous microbial biomass, while iron sulphate exerted a direct abiotic role.

Effectiveness of radioiodine (131-I) as definitive therapy in patients with autoimmune and non-autoimmune hyperthyroidism.

PubMed

Tarantini, B; Ciuoli, C; Di Cairano, G; Guarino, E; Mazzucato, P; Montanaro, A; Burroni, L; Vattimo, A G; Pacini, F

2006-01-01

We evaluated the outcome of radioiodine (RAI) therapy in 100 consecutive patients treated in the period 2000-2001 for hyperthyroidism due to Graves' disease (GD), toxic adenoma (TA) and toxic multinodular goiter (TMG). Thyroid function was measured before and after therapy every 3-6 months up to 3 yr. Three years after therapy, 75% of TA patients were euthyroid, 18.7% were hypothyroid and 6.3% hyperthyroid. Of the TMG patients, 62.2% were euthyroid, 18.9% were hypothyroid and 18.9% hyperthyroid. In GD patients euthyroidism was achieved in 12.9% of the patients, hypothyroidism in 74.2% and hyperthyroidism persisted in 12.9%. Definitive hypothyroidism was significantly higher in GD (p<0.0001) than in TA and TMG patients. Overall, positive effect of RAI (definitive hypothyroidism or euthyroidism) was very high: 93.7% in TA, 81.1% in TMG and 87.1% in GD patients. Thyroid volume reduction was observed in all patients, but was higher in GD patients (mean reduction of 76%) and in TA patients (mean nodule reduction of 69%). In TMG, mean reduction was of 32%. The median activity of RAI received by the 86 cured patients was 555 MBq (15 mCi) compared to 407 Mbq (11 mCi) received by the 14 patients who remained hyperthyroid. No influence was found between outcome and clinical parameters at the moment of 131-I therapy. In conclusion, our results indicate that RAI therapy is highly effective and safe for the control of hyperthyroidism.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodgson, Alfred T.; Fisk, William J.; Shendell, Derek G.

Relocatable classrooms (RCs) are widely employed by California school districts to satisfy rapidly expanding space requirements due to population growth and class size reduction policies. There is public concern regarding indoor environmental quality (IEQ) in schools, particularly in RCs, but very little data to support or dispel these concerns. Several studies are investigating various aspects of IEQ in California schools. This laboratory-based study focused on evaluating the emissions of toxic and/or odorous volatile organic compounds (VOCs), including formaldehyde and acetaldehyde, from materials used to finish the interiors of new RCs. Furthermore, the study implemented a procedure for VOC source reductionmore » by testing and selecting lower-emitting materials as substitutes for standard materials. In total, 17 standard and alternate floor coverings, wall panels and ceiling panels were quantitatively tested for emissions of VOCs using smallscale environmental chambers. Working with the largest northern California manufacturer of conventional RCs and two school districts, specifications were developed for four new RCs to be produced in early summer 2001. Two of these will be predominantly finished with standard materials. Alternate carpet systems, an alternate wall panel covering and an alternate ceiling panel were selected for the two other RCs based on the results of the laboratory study and considerations of cost and anticipated performance and maintenance. Particular emphasis was placed on reducing the concentrations of VOCs on California agency lists of toxic compounds. Indoor concentrations of toxic and odorous VOCs were estimated for the four classrooms by mass balance using the measured VOC emission factors, exposed surface areas of the materials in the RCs, and three ventilation rate scenarios. Results indicate that reductions in the concentrations of formaldehyde, acetaldehyde phenol, di(ethylene glycol) butyl ether, vinyl acetate, 1,2,4-trimethylbenzene and 1-methyl-2-pyrrolidinone should be achieved as the result of the source reduction procedure.« less

Managing toxicities and optimal dosing of targeted drugs in advanced kidney cancer

PubMed Central

Seruga, B.; Gan, H.K.; Knox, J.J.

2009-01-01

The toxicities of new, targeted drugs may diminish their effectiveness in advanced kidney cancer if those toxicities are not recognized and properly addressed early in patient treatment. Most of the drug-related toxicities in advanced kidney cancer are manageable with supportive care, obviating a need for long interruptions, dose reductions, or permanent discontinuation of the treatment. PMID:19478903

Multi-class Mode of Action Classification of Toxic Compounds Using Logic Based Kernel Methods.

PubMed

Lodhi, Huma; Muggleton, Stephen; Sternberg, Mike J E

2010-09-17

Toxicity prediction is essential for drug design and development of effective therapeutics. In this paper we present an in silico strategy, to identify the mode of action of toxic compounds, that is based on the use of a novel logic based kernel method. The technique uses support vector machines in conjunction with the kernels constructed from first order rules induced by an Inductive Logic Programming system. It constructs multi-class models by using a divide and conquer reduction strategy that splits multi-classes into binary groups and solves each individual problem recursively hence generating an underlying decision list structure. In order to evaluate the effectiveness of the approach for chemoinformatics problems like predictive toxicology, we apply it to toxicity classification in aquatic systems. The method is used to identify and classify 442 compounds with respect to the mode of action. The experimental results show that the technique successfully classifies toxic compounds and can be useful in assessing environmental risks. Experimental comparison of the performance of the proposed multi-class scheme with the standard multi-class Inductive Logic Programming algorithm and multi-class Support Vector Machine yields statistically significant results and demonstrates the potential power and benefits of the approach in identifying compounds of various toxic mechanisms. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Organic compounds removal and toxicity reduction of landfill leachate by commercial bakers' yeast and conventional bacteria based membrane bioreactor integrated with nanofiltration.

PubMed

Reis, Beatriz Gasparini; Silveira, Amanda Lemes; Tostes Teixeira, Luiza Procópio; Okuma, Adriana Akemi; Lange, Liséte Celina; Amaral, Miriam Cristina Santos

2017-12-01

This study aimed to compare the performance of a commercial bakers' yeast (MBRy) and conventional bacteria (MBRb) based membrane bioreactor integrated with nanofiltration (NF) in the removal of landfill leachate toxicity. Performances were evaluated using physicochemical analyses, toxicity tests and identification of organic compounds. The MBR b and MBR y were operated with a hydraulic retention time (HRT) of 48h and solids retention time (SRT) of 60 d. The MBR y demonstrated better removal efficiencies for COD (69±7%), color (54±11%) and ammoniacal nitrogen (34±7%) compared to MBR b , which showed removal efficiencies of 27±5%, 33±4% and 27±7%, for COD, color and ammoniacal nitrogen. Although the MBR y seems to be the configuration that presented the highest efficiency; it generated toxic permeate whose toxicity cannot be explained by physicochemical results. The identification of compounds shows that there is a wide range of compounds in the landfill leachate in addition to others that are produced in the biological treatment steps. The NF plays a crucial role in the polishing of the final effluents by the either complete or partial retention of compounds, that attribute toxicity to the leachate, and inorganic contaminants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protective effect of vitamins e and C on endosulfan-induced reproductive toxicity in male rats.

PubMed

Takhshid, Mohammad Ali; Tavasuli, Ali Reza; Heidary, Yazdan; Keshavarz, Mojtaba; Kargar, Hussain

2012-09-01

The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats. Fifty adult male Sprague-Dawley rats were randomly divided into five groups (n=10 each). The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day) alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day), vitamin E (200 mg/kg/day), or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH), plasma testosterone and malondialdehyde (MDA) levels in the testis were determined. Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP) and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan. The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

FULL-SCALE TESTS OF THE MULTI-CHAMBERED TREATMENT TANK (MCTT)

EPA Science Inventory

The MCTT was developed to control toxicants in stormwater from critical source areas. During monitoring, the pilot-scale MCTT provided median reductions of >90% for toxicity, lead, zinc, and most organic toxicants. Suspended solids was reduced by 83% and COD was reduced by 60%. T...

Photodegradation of Mefenamic Acid in Aqueous Media: Kinetics, Toxicity and Photolysis Products.

PubMed

Chen, Ping; Wang, Feng Liang; Yao, Kun; Ma, Jing Shuai; Li, Fu Hua; Lv, Wen Ying; Liu, Guo Guang

2016-02-01

The present study investigated the photolytic behavior and photodegradation products of mefenamic acid (MEF) under ultraviolet-C irradiation. The results demonstrated that the photodegradation of MEF followed pseudo-first-order kinetics and the direct photolysis quantum yield of mefenamic acid was observed to be 2.63 ± 0.28 × 10⁻³. Photodegradation of MEF included degradation by direct photolysis and by self-sensitization that the contribution rates of self-sensitized photodegradation were 5.70, 11.25 and 18.96 % for ·OH, ¹O₂ and O·₂⁻ , respectively. Primary transformation products of MEF were identified using ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometer (UPLC-Q-TOF-MS). The identified transformation products suggested three possible pathways of MEF photodegradation: dehydrogenation, hydroxylation, and ketonized reactions. Toxicity of phototransformation products were evaluated using the Microtox test, which revealed that photodegradation likely provides a critical pathway for MEF toxicity reduction in drinking water and wastewater treatment facilities.

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

PubMed

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 < 0.05). The toxicity results indicate that the environmental hazardous risks of the relevant ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential toxicity, conformation and morphology of typical initial aggregation states of Aβ1-42 and Aβpy3-42 beta-amyloids.

PubMed

Galante, Denise; Corsaro, Alessandro; Florio, Tullio; Vella, Serena; Pagano, Aldo; Sbrana, Francesca; Vassalli, Massimo; Perico, Angelo; D'Arrigo, Cristina

2012-11-01

Among the different species of water-soluble β-peptides (Aβ1-42, Aβ1-40 and N-terminal truncated Aβ-peptides), Aβpy3-42 is thought to play a relevant role in Alzheimer's pathogenesis due to its abundance, resistance to proteolysis, fast aggregation kinetics, dynamic structure and high neurotoxicity. To evaluate the specific structural characteristics and neurotoxicity of Aβpy3-42, we separated different aggregation states of Aβ1-42 and Aβpy3-42 using fast protein liquid chromatography, isolating in both cases three peaks that corresponded to sa (small), ma (medium) and la (large) aggregates. Conformational analysis, by circular dichroism showed a prevailing random coil conformation for sa and ma, and typical β-sheet conformation for la. AFM and TEM show differential structural features between the three aggregates of a given β-peptide and among the aggregate of the two β-peptides. The potential toxic effects of the different aggregates were evaluated using human neuroblastoma SH-SY5Y cells in the MTT reduction, in the xCELLigence System, and in the Annexin V binding experiments. In the case of Aβ1-42 the most toxic aggregate is la, while in the case of Aβpy3-42 both sa and la are equally toxic. Aβ aggregates were found to be internalized in the cells, as estimated by confocal immunofluorescence microscopy, with a higher effect observed for Aβpy3-42, showing a good correlation with the toxic effects. Together these experiments allowed the discrimination of the intermediate states more responsible of oligomer toxicity, providing new insights on the correlation between the aggregation process and the toxicity and confirming the peculiar role in the pathogenesis of Alzheimer disease of Aβpy3-42 peptide. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ethanol extract of Moringa oliefera prevents in vitro glucose induced cataract on isolated goat eye lens.

PubMed

Kurmi, Raghvendra; Ganeshpurkar, Aditya; Bansal, Divya; Agnihotri, Abhishek; Dubey, Nazneen

2014-02-01

The aim of current work was to evaluate in vitro anticataract potential of Moringa oliefera extract. Goat eye lenses were divided into 4 groups; Group served as control, Group II as toxic control, Group III and Group IV were incubated in extract (250 μg/ml and 500 μg/ml of extract of M. oliefera) Group II, III and IV were incubated in 55 mM glucose in artificial aqueous humor to induce lens opacification. Estimation of total, water soluble protein, catalase, glutathione and malondialdehyde along with photographic evaluation of lens was done. Group II (toxic control) lenses showed high amount of MDA (Malondialdehyde), soluble, insoluble protein, decreased catalase and glutathione levels, while lenses treated with Moringa oliefera extract (Group III and Group IV) showed significant (FNx01 P < 0.05) reduction in MDA and increased level of catalase, glutathione, total and soluble protein. Results of present findings suggest protective effect of Moringa oliefera in prevention of in vitro glucose induced cataract.

Reported Barriers to Source Reduction in the 2015 TRI National Analysis

EPA Pesticide Factsheets

Source Reduction/Pollution Prevention - barriers to implementing source reduction activities as reported by facilities for the 2015 Toxics Release Inventory National Analysis, including examples of each type of barrier

Reported Barriers to Source Reduction in the 2016 TRI National Analysis

EPA Pesticide Factsheets

Source Reduction/Pollution Prevention - barriers to implementing source reduction activities as reported by facilities for the 2016 Toxics Release Inventory National Analysis, including examples of each type of barrier

Catalytic efficiency of macrocyclic-capped gold nanoparticles: cucurbit[n]urils versus cyclodextrins

NASA Astrophysics Data System (ADS)

del Pozo, María; Blanco, Elías; Hernández, Pedro; Casas, José A.; Quintana, Carmen

2018-05-01

In this work, different macrocyclic systems, belonging to cucurbit[n]urils and cyclodextrins families, were employed as stabilizers of gold nanoparticles and their performance as catalysts in the reduction reaction of the toxic 4-nitrophenol to produce the valuable 4-aminophenol, was evaluated. To this goal, six nanosystems were prepared and compared under identical experimental conditions. The influence that (i) differences in shape, (ii) nature of chemical groups constituting the receptor entrances and (iii) differences in the portal sizes of those stabilizing agents have in the activity of these nanoparticles as catalysts in a nitro compound reduction reaction is evaluated and discussed. The TEM characterization of the nanocatalysts prepared is included. From these data, nanoparticles ranging from 3.7-10.7 nm in diameter, depending on the stabilizer employed, were obtained. The evaluation of kinetic rate constants normalized respect to gold concentration and catalyst surface for each system is included and discussed. In addition, the stability of the different nanocatalyst depending on the capping agent employed is also evaluated. [Figure not available: see fulltext.

Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study.

PubMed

Maggi, Paolo; Montinaro, Vincenzo; Leone, Armando; Fasano, Massimo; Volpe, Anna; Bellacosa, Chiara; Grattagliano, Vito; Coladonato, Laura; Lapadula, Giovanni; Santantonio, Teresa; Angarano, Gioacchino

2015-04-01

Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2). During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

PubMed

Jasim, Sina; Iniguez-Ariza, Nicole M; Hilger, Crystal R; Chintakuntlawar, Ashish V; Ryder, Mabel M; Morris, John C; Bible, Keith C

2017-10-01

Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. DTC = differentiated thyroid cancer; LASA = linear analog self-assessment; PR = partial response; QOL = quality of life; RAI = radioactive iodine; RAIR = RAI-resistant; RECIST = Response Evaluation Criteria In Solid Tumors; Tg = thyroglobulin; VEGFR = vascular endothelial growth factor receptor.

Evaluation of Nephroprotective and Immunomodulatory Activities of Antioxidants in Combination with Cisplatin against Murine Visceral Leishmaniasis

PubMed Central

Sharma, Meenakshi; Sehgal, Rakesh; Kaur, Sukhbir

2012-01-01

Background Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. An antineoplastic drug, cisplatin (cis-diamminedichloroplatinum II; CDDP), is recognized as a DNA-damaging drug which also induces alteration of cell-cycle in both promastigotes and amastigotes leading to cell death. First in vivo reports from our laboratory revealed the leishmanicidal potential of cisplatin. However, high doses of cisplatin produce impairment of kidney, which can be reduced by the administration of antioxidants. Methodology/Principal Findings The present study was designed to evaluate the antileishmanial effect of cisplatin at higher doses (5 mg and 2.5 mg/kg body weight) and its combination with different antioxidants (vitamin C, vitamin E and silibinin) so as to eliminate the parasite completely and reduce the toxicity. In addition, various immunological, hematological and biochemical changes induced by it in uninfected and Leishmania donovani infected BALB/c mice were investigated. Conclusion/Significance A significant reduction in parasite load, higher IgG2a and lower IgG1 levels, enhanced DTH responses, and greater concentration of Th1 cytokines (IFN-γ, IL-2) with a concomitant down regulation of IL-10 and IL-4 pointed towards the generation of the protective Th1 type of immune response. A combination of cisplatin with antioxidants resulted in successful reduction of nephrotoxicity by normalizing the enzymatic levels of various liver and kidney function tests. Reduction in parasite load, increase in Th1 type of immune responses, and normalization of various biochemical parameters occurred in animals treated with cisplatin in combination with various antioxidants as compared to those treated with the drug only. The above results are promising as antioxidants reduced the potential toxicity of high doses of cisplatin, making the combination a potential anti-leishmanial therapy, especially in resistant cases. PMID:22563510

Reduction of Fumonisin Toxicity by Extrusion and Nixtamalization (Alkaline Cooking)

USDA-ARS?s Scientific Manuscript database

Fumonisins are found in corn. They are toxic to animals, cause cancer in rodents, and neural tube defects in LM/Bc mice. Reducing their concentrations in corn-based foods is therefore desirable. Chemical analysis or in vitro bioassays of food extracts might not detect toxic fumonisin reaction pro...

TOXICITY TRENDS DURING AN OIL SPILL BIOREMEDIATION EXPERIMENT ON A SANDY SHORELINE IN DELAWARE, USA

EPA Science Inventory

A 13-week, refereed, inter-agency toxicity testing program involving five bioassay methods was used to document the effectiveness of shoreline bioremediation to accelerate toxicity reduction of an oiled sandy shoreline at Fowler Beach, Delaware, USA. The study was part of an inte...

Integrating Hazardous Materials Characterization and Assessment Tools to Guide Pollution Prevention in Electronic Products and Manufacturing

NASA Astrophysics Data System (ADS)

Lam, Carl

Due to technology proliferation, the environmental burden attributed to the production, use, and disposal of hazardous materials in electronics have become a worldwide concern. The major theme of this dissertation is to develop and apply hazardous materials assessment tools to systematically guide pollution prevention opportunities in the context of electronic product design, manufacturing and end-of-life waste management. To this extent, a comprehensive review is first provided on describing hazard traits and current assessment methods to evaluate hazardous materials. As a case study at the manufacturing level, life cycle impact assessment (LCIA)-based and risk-based screening methods are used to quantify chemical and geographic environmental impacts in the U.S. printed wiring board (PWB) industry. Results from this industrial assessment clarify priority waste streams and States to most effectively mitigate impact. With further knowledge of PWB manufacturing processes, select alternative chemical processes (e.g., spent copper etchant recovery) and material options (e.g., lead-free etch resist) are discussed. In addition, an investigation on technology transition effects for computers and televisions in the U.S. market is performed by linking dynamic materials flow and environmental assessment models. The analysis forecasts quantities of waste units generated and maps shifts in environmental impact potentials associated with metal composition changes due to product substitutions. This insight is important to understand the timing and waste quantities expected and the emerging toxic elements needed to be addressed as a consequence of technology transition. At the product level, electronic utility meter devices are evaluated to eliminate hazardous materials within product components. Development and application of a component Toxic Potential Indicator (TPI) assessment methodology highlights priority components requiring material alternatives. Alternative recommendations are provided and substitute materials such as aluminum alloys for stainless steel and high-density polyethylene for polyvinyl chloride and acrylonitrile-based polymers show promise to meet toxicity reduction, cost, and material functionality requirements. Furthermore, the TPI method, an European Union focused screening tool, is customized to reflect regulated U.S. toxicity parameters. Results show that, although it is possible to adopt U.S. parameters into the TPI method, harmonization of toxicity regulation and standards in various nations and regions is necessary to eliminate inconsistencies during hazard screening of substances used globally. As a whole, the present work helps to assimilate material hazard assessment methods into the larger framework of design for environment strategies so toxics use reduction could be achieved for the development and management of electronics and other consumer goods.

Environmental transformations and ecological effects of iron-based nanoparticles.

PubMed

Lei, Cheng; Sun, Yuqing; Tsang, Daniel C W; Lin, Daohui

2018-01-01

The increasing application of iron-based nanoparticles (NPs), especially high concentrations of zero-valent iron nanoparticles (nZVI), has raised concerns regarding their environmental behavior and potential ecological effects. In the environment, iron-based NPs undergo physical, chemical, and/or biological transformations as influenced by environmental factors such as pH, ions, dissolved oxygen, natural organic matter (NOM), and biotas. This review presents recent research advances on environmental transformations of iron-based NPs, and articulates their relationships with the observed toxicities. The type and extent of physical, chemical, and biological transformations, including aggregation, oxidation, and bio-reduction, depend on the properties of NPs and the receiving environment. Toxicities of iron-based NPs to bacteria, algae, fish, and plants are increasingly observed, which are evaluated with a particular focus on the underlying mechanisms. The toxicity of iron-based NPs is a function of their properties, tolerance of test organisms, and environmental conditions. Oxidative stress induced by reactive oxygen species is considered as the primary toxic mechanism of iron-based NPs. Factors influencing the toxicity of iron-based NPs are addressed and environmental transformations play a significant role, for example, surface oxidation or coating by NOM generally lowers the toxicity of nZVI. Research gaps and future directions are suggested with an aim to boost concerted research efforts on environmental transformations and toxicity of iron-based NPs, e.g., toxicity studies of transformed NPs in field, expansion of toxicity endpoints, and roles of laden contaminants and surface coating. This review will enhance our understanding of potential risks of iron-based NPs and proper uses of environmentally benign NPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Paracetamol degradation intermediates and toxicity during photo-Fenton treatment using different iron species.

PubMed

Trovó, Alam G; Pupo Nogueira, Raquel F; Agüera, Ana; Fernandez-Alba, Amadeo R; Malato, Sixto

2012-10-15

The photo-Fenton degradation of paracetamol (PCT) was evaluated using FeSO(4) and the iron complex potassium ferrioxalate (FeOx) as iron source under simulated solar light. The efficiency of the degradation process was evaluated considering the decay of PCT and total organic carbon concentration and the generation of carboxylic acids, ammonium and nitrate, expressed as total nitrogen. The results showed that the degradation was favored in the presence of FeSO(4) in relation to FeOx. The higher concentration of hydroxylated intermediates generated in the presence of FeSO(4) in relation to FeOx probably enhanced the reduction of Fe(III) to Fe(II) improving the degradation efficiency. The degradation products were determined using liquid chromatography electrospray time-of-flight mass spectrometry. Although at different concentrations, the same intermediates were generated using either FeSO(4) or FeOx, which were mainly products of hydroxylation reactions and acetamide. The toxicity of the sample for Vibrio fischeri and Daphnia magna decreased from 100% to less than 40% during photo-Fenton treatment in the presence of both iron species, except for D. magna in the presence of FeOx due to the toxicity of oxalate to this organism. The considerable decrease of the sample toxicity during photo-Fenton treatment using FeSO(4) indicates a safe application of the process for the removal of this pharmaceutical. Copyright © 2012 Elsevier Ltd. All rights reserved.

Use of an alpha lipoic, methylsulfonylmethane and bromelain dietary supplement (Opera®) for chemotherapy-induced peripheral neuropathy management, a prospective study.

PubMed

Desideri, Isacco; Francolini, Giulio; Becherini, Carlotta; Terziani, Francesca; Delli Paoli, Camilla; Olmetto, Emanuela; Loi, Mauro; Perna, Marco; Meattini, Icro; Scotti, Vieri; Greto, Daniela; Bonomo, Pierluigi; Sulprizio, Susanna; Livi, Lorenzo

2017-03-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical problem associated with a number of cytotoxic agents. OPERA ® (GAMFARMA srl, Milan, Italy) is a new dietary supplement where α-lipoic acid, Boswellia Serrata, methylsulfonylmethane and bromelain are combined in a single capsule. The aim of this prospective study was to determine the efficacy and safety of OPERA ® supplementation in a series of patients affected by CIPN. We selected 25 subjects with CIPN evolving during or after chemotherapy with potentially neurotoxic agents. Patients were enrolled at the first clinical manifestation of neuropathy. CIPN was assessed at the enrollment visit and subsequently repeated every 3 weeks until 12 weeks. Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA ® . Analysis of VAS data showed reduction in pain perceived by patients. According to NCI-CTC sensor and motor score, mISS scale and TNSc scale, both pain and both sensor and motor neuropathic impairment decreased after 12 weeks of treatments. Treatment with OPERA supplement was well tolerated; no increase in the toxicity profile of any of the therapeutic regimen that the patients were undergoing was reported. OPERA ® was able to improve CIPN symptoms in a prospective series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. Prospective RCT in a selected patients' population is warranted to confirm its promising activity.

Single-Cell Imaging and Spectroscopic Analyses of Cr(VI) Reduction on the Surface of Bacterial Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yuanmin; Sevinc, Papatya C.; Belchik, Sara M.

2013-01-22

We investigate single-cell reduction of toxic Cr(VI) by the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), an important bioremediation process, using Raman spectroscopy and scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDX). Our experiments indicate that the toxic and highly soluble Cr(VI) can be efficiently reduced to the less toxic and non-soluble Cr2O3 nanoparticles by MR-1. Cr2O3 is observed to emerge as nanoparticles adsorbed on the cell surface and its chemical nature is identified by EDX imaging and Raman spectroscopy. Co-localization of Cr2O3 and cytochromes by EDX imaging and Raman spectroscopy suggests a terminal reductase role for MR-1more » surface-exposed cytochromes MtrC and OmcA. Our experiments revealed that the cooperation of surface proteins OmcA and MtrC makes the reduction reaction most efficient, and the sequence of the reducing reactivity of the MR-1 is: wild type > single mutant @mtrC or mutant @omcA > double mutant (@omcA-@mtrC). Moreover, our results also suggest that the direct microbial Cr(VI) reduction and Fe(II) (hematite)-mediated Cr(VI) reduction mechanisms may co-exist in the reduction processes.« less

Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay.

PubMed

Peixoto, Raphael Cândido Apolinário; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Carneiro, Marcella Lemos' Brettas; Oliveira, Ricardo G S; da Silva, Matheus Oliveira; de Souza, Aparecido R; Báo, Sônia Nair

2015-05-01

Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.

Fast and sensitive optical toxicity bioassay based on dual wavelength analysis of bacterial ferricyanide reduction kinetics.

PubMed

Pujol-Vila, F; Vigués, N; Díaz-González, M; Muñoz-Berbel, X; Mas, J

2015-05-15

Global urban and industrial growth, with the associated environmental contamination, is promoting the development of rapid and inexpensive general toxicity methods. Current microbial methodologies for general toxicity determination rely on either bioluminescent bacteria and specific medium solution (i.e. Microtox(®)) or low sensitivity and diffusion limited protocols (i.e. amperometric microbial respirometry). In this work, fast and sensitive optical toxicity bioassay based on dual wavelength analysis of bacterial ferricyanide reduction kinetics is presented, using Escherichia coli as a bacterial model. Ferricyanide reduction kinetic analysis (variation of ferricyanide absorption with time), much more sensitive than single absorbance measurements, allowed for direct and fast toxicity determination without pre-incubation steps (assay time=10 min) and minimizing biomass interference. Dual wavelength analysis at 405 (ferricyanide and biomass) and 550 nm (biomass), allowed for ferricyanide monitoring without interference of biomass scattering. On the other hand, refractive index (RI) matching with saccharose reduced bacterial light scattering around 50%, expanding the analytical linear range in the determination of absorbent molecules. With this method, different toxicants such as metals and organic compounds were analyzed with good sensitivities. Half maximal effective concentrations (EC50) obtained after 10 min bioassay, 2.9, 1.0, 0.7 and 18.3 mg L(-1) for copper, zinc, acetic acid and 2-phenylethanol respectively, were in agreement with previously reported values for longer bioassays (around 60 min). This method represents a promising alternative for fast and sensitive water toxicity monitoring, opening the possibility of quick in situ analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Nitrate-induced photodegradation of atenolol in aqueous solution: kinetics, toxicity and degradation pathways.

PubMed

Ji, Yuefei; Zeng, Chao; Ferronato, Corinne; Chovelon, Jean-Marc; Yang, Xi

2012-07-01

The extensive utilization of β-blockers worldwide led to frequent detection in natural water. In this study the photolysis behavior of atenolol (ATL) and toxicity of its photodegradation products were investigated in the presence of nitrate ions. The results showed that ATL photodegradation followed pseudo-first-order kinetics upon simulated solar irradiation. The photodegradation was found to be dependent on nitrate concentration and increasing the nitrate from 0.5 mML(-1) to 10 mML(-1) led to the enhancement of rate constant from 0.00101 min(-1) to 0.00716 min(-1). Hydroxyl radical was determined to play a key role in the photolysis process by using isopropanol as molecular probe. Increasing the solution pH from 4.8 to 10.4, the photodegradation rate slightly decreased from 0.00246 min(-1) to 0.00195 min(-1), probably due to pH-dependent effect of nitrate-induced .OH formation. Bicarbonate decreased the photodegradation of ATL in the presence of nitrate ions mainly through pH effect, while humic substance inhibited the photodegradation via both attenuating light and competing radicals. Upon irradiation for 240 min, only 10% reduction of total organic carbon (TOC) can be achieved in spite of 72% transformation rate of ATL, implying a majority of ATL transformed into intermediate products rather than complete mineralization. The main photoproducts of ATL were identified by using solid phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) techniques and possible nitrate-induced photodegradation pathways were proposed. The toxicity of the phototransformation products was evaluated using aquatic species Daphnia magna, and the results revealed that photodegradation was an effective mechanism for ATL toxicity reduction in natural waters. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice.

PubMed

Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

Kidney is a vital organ which plays an important and irreplaceable role in detoxification and removal of xenobiotics. And therefore is vulnerable to develop various forms of injuries. Hence, making it immensely important to search for natural reno-protective compounds. This study therefore, aims to evaluate the reno-protective properties of propolis against gentamicin induced renal toxicity in mice. Three groups of 10 male mice each were used for this study. First group served as control, the second group (Gm group) was administered orally 80mg/kg body weight gentamicin for 7 days, and the third group (GmP group) was administered same dose of gentamicin with propolis (500mg/kg body weight) for 7 days. Various parameters were used to study the renal toxicity. Gentamicin caused significant renal damage as evident by the rise in BUN levels, diminished glomeruli hypocellularity, moderately dilated tubules, and mild loss of brush border, severe infiltration, extensive tubular degeneration and presence of tubular cast. Histochemistry results show presence of collagen and reticular fibres. Immunohistochemical reactions show kidney injury (Kim-1 gene-expression), oxidative stress (MDA gene-expression), and an increase in apoptosis (caspase-3 gene-expression). Co-administration of propolis with gentamicin showed significant decrease in BUN levels, appearance of healthy glomeruli with normal cellularity, reduction of tubular injury, decrease of collagen and reticular fibres deposition, reduction of apoptosis, kidney injury and oxidative stress. Results presented in this study clearly show the reno-protective role of propolis against gentamicin-induced toxicity on mice kidney. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

The Effects of Mangiferin (Mangifera indica L) in Doxorubicin-induced Cardiotoxicity in Rats.

PubMed

Arozal, W; Suyatna, F D; Juniantito, V; Rosdiana, D S; Amurugam, S; Aulia, R; Monayo, E R; Siswandi, R

2015-11-01

The cardiotoxicity effect of doxorubicin (DOX), a widely used antitumor agent has restricted its clinical application. The aim of the current study was to explore the potential protective effect of mangiferin, a naturally occurring glucosylxanthone, that have antioxidant activity by its iron-complexing ability in mitochondria, against DOX-induced cardiac toxicity in rats in comparison with other antioxidants namely Sylimarin (SYL) and Vitamin E (VitE). Mangiferin was given orally to rats at a dose of 50, and 100 mg/kg for 5 weeks, and DOX was injected at a total dose of 15 mg/kg. Cardiac toxicity was evaluated by lactate dehydrogenase and creatine kinase in the serum, malondialdehyde (MDA) level in plasma and cardiac tissue, and antioxidant enzyme superoxide dismutase (SOD) in cardiac tissue. Mangiferin protected against DOX-induced increased mortality and electrocardiogram abnormality and decreased biochemical markers of cardiac toxicity i. e., lactate dehydrogenase and creatine phosphokinase isoenzyme. In addition, elevation of plasma and cardiac tissue levels of MDA in response to DOX treatment were significantly attenuated. The reduction of cardiac activity of SOD was significantly reduced in contrast with the other antioxidant SYL and Vit E. Histopathologically, mangiferin treatment showed significant reduction in inflammatory cell number, fibrotic area, and necrotic foci as compared with DOX only-treated rats. These results suggested that mangiferin had better protective effect against DOX-induced cardiac toxicity in comparison with SYL and VitE, thus besides the antioxidant activity, different mechanism may be involved in the action of mangiferin and need to be clarified in the future studies. © Georg Thieme Verlag KG Stuttgart · New York.

Environmental impacts of remediation of a trichloroethene-contaminated site: life cycle assessment of remediation alternatives.

PubMed

Lemming, Gitte; Hauschild, Michael Z; Chambon, Julie; Binning, Philip J; Bulle, Cécile; Margni, Manuele; Bjerg, Poul L

2010-12-01

The environmental impacts of remediation of a chloroethene-contaminated site were evaluated using life cycle assessment (LCA). The compared remediation options are (i) in situ bioremediation by enhanced reductive dechlorination (ERD), (ii) in situ thermal desorption (ISTD), and (iii) excavation of the contaminated soil followed by off-site treatment and disposal. The results showed that choosing the ERD option will reduce the life-cycle impacts of remediation remarkably compared to choosing either ISTD or excavation, which are more energy-demanding. In addition to the secondary impacts of remediation, this study includes assessment of local toxic impacts (the primary impact) related to the on-site contaminant leaching to groundwater and subsequent human exposure via drinking water. The primary human toxic impacts were high for ERD due to the formation and leaching of chlorinated degradation products, especially vinyl chloride during remediation. However, the secondary human toxic impacts of ISTD and excavation are likely to be even higher, particularly due to upstream impacts from steel production. The newly launched model, USEtox, was applied for characterization of primary and secondary toxic impacts and combined with a site-dependent fate model of the leaching of chlorinated ethenes from the fractured clay till site.

Evaluation of the toxic potential of calcium carbide in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9).

PubMed

Danish, Mohd; Fatima, Ambreen; Khanam, Saba; Jyoti, Smita; Rahul; Ali, Fahad; Naz, Falaq; Siddique, Yasir Hasan

2015-11-01

In the present study the toxic potential of calcium carbide (CaC2) was studied on the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg(9). The third instar larvae were exposed to 2, 4, 8, 16 and 32×10(-3)g/ml of CaC2 in diet for 24h. The results reveal that the dose 2×10(-3)g/ml was not toxic but the remaining doses showed a dose dependent significant increase in the hsp70 expression, β-galactosidase activity, tissue damage, oxidative stress markers (lipid peroxidation and protein carbonyl content), glutathione-S-transferase activity, expression of Caspase 3 and 9, apoptotic index and DNA damage (midgut cells). A significant reduction as compared to control group in total protein, glutathione content and acetylcholinesterase activity was also observed. The Inductively Coupled Plasma Atomic Emission Spectroscopy analysis (ICPAES) reveals the presence of copper, iron, sodium, aluminium, manganese, calcium, nickel and mercury. The toxic effects of CaC2 in the present study may be attributed to the impurities present in it. Copyright © 2015 Elsevier Ltd. All rights reserved.

Direct viable count as test for toxicity assessment: the effects of four metals on a Salmonella enteritidis strain.

PubMed

Scoglio, M E; Di Pietro, A; Anzalone, C; Calimeri, S; Lo Giudice, D; Trimarchi, G R

2000-01-01

The toxicity of synthetic sewage containing increasing concentrations of arsenic (.125, .25, .5, 1.0 mg L-1), cadmium (.02, .05, .1, .2 mg L-1), lead (.2, .5, 1.0, 2.0 mg L-1) and nickel (.5, 1.0, 2.0, 4.0 mg L-1) has been investigated by determining the total direct count (TDC) and the direct viable count (DVC) of Salmonella enteritidis by means of an immunofluorescence technique (IFA). This has been done in order to evaluate the possibility of using the IFA technique to estimate the toxicity of complex effluents. Arsenic, cadmium and nickel produced a concentration-dependent reduction in the number of viable bacterial cells. This was more clear when the viable bacterial cells were considered than when only the culturable part was used. Lead did not show a concentration-dependent and reproducible effect. At the highest concentrations allowed by the Italian wastewater regulations, lead, cadmium, arsenic and nickel reduced the viable/total bacterial cells ratio to 74.5%, 68.5%, 28.4% and 6.9%, respectively. The toxic effects of the metals were also tested using the standard Microtox assay.

Epithelial toxicity of alkylglycoside surfactants.

PubMed

Vllasaliu, Driton; Shubber, Saif; Fowler, Robyn; Garnett, Martin; Alexander, Cameron; Stolnik, Snow

2013-01-01

Alkylglycoside surfactants have been proposed as drug delivery excipients with the potential to enhance mucosal drug absorption of therapeutic macromolecules. Previous work reported their drug absorption-promoting potential by demonstrating that several compounds within this class of surfactants improve mucosal absorption of peptides, proteins and other macromolecules. However, detailed investigation of their toxicity has not been conducted. Using Calu-3 epithelial cell layers as a model of the airway mucosa, and liposomes as models of cell membranes, this work investigates the cytotoxicity of dodecylmaltoside, tridecylmaltoside and tetradecylmaltoside, as representative alkylglycosides. A combination of different toxicity assays and other tests indicating cell membrane disruption were used to assess cytotoxicity. The alkylglycosides tested induced a dramatic reduction in cell viability, cell membrane and liposome-disruptive effects, as well as abrogation of transepithelial electrical resistance that did not recover completely. Importantly, these phenomena were noted at concentrations markedly lower than those typically used in the literature studies demonstrating the absorption-enhancing properties of alkylglycosides. This work therefore demonstrates that alkylglycosides exhibit significant toxicity towards airway epithelial cells, most likely resulting from a membrane-damaging effect, highlighting a need for further evaluation of their safety as absorption-enhancing excipients. Copyright © 2012 Wiley Periodicals, Inc.

Toxicity of Piper aduncum (Piperaceae) Essential Oil Against Euschistus heros (F.) (Hemiptera: Pentatomidae) and Non-Effect on Egg Parasitoids.

PubMed

Turchen, L M; Piton, L P; Dall'Oglio, E L; Butnariu, A R; Pereira, M J B

2016-10-01

Plant essential oils have been recognized as significant natural resources for insecticides. Herein, we have assessed the toxicity of the essential oil of Piper aduncum (Piperaceae) against Euschistus heros (F.) (Hemiptera: Pentatomidae), a key soybean pest in Neotropical America. In addition, we have assessed its effect on the performance of egg parasitoids. The essential oil was obtained from the leaves of P. aduncum via hydrodistillation. Subsequently, bioassays of the concentration response to eggs (contact and immersion methods), nymphs, and adults (topical application) were conducted, to assess the lethal effects on the stink bug. We also evaluated the performance of parasitism and adult emergence of egg parasitoids, when the host eggs were treated with essential oil. In the egg bioassay, both exposure methods were efficient for unviable eggs (immersion LC 50  = 15.64 mg mL -1 ; contact LC 50  = 21.29 mg mL -1 ), with the highlight on the immersion method. The bioassay with nymphs indicated a higher toxicity of essential oil, with lower concentrations (LC 50  = 11.37 mg mL -1 ) being required to cause the death of insects. For adults, a reduction in survival of insects was observed, and consequently, there was a reduction in the number of individuals in the next generation. Although the essential oil was toxic to E. heros, it exhibited lower toxicity for egg parasitoids, as there was no effect on parasitism and the emergence of wasps. We discuss likely explanations for such selectivity. In summary, we found that the essential oil was promising for the control of E. heros, because it caused deleterious effects at all development stages of the stink bug and had no effect on parasitism and emergence of the egg parasitoids, which suggested compatibility with biological control.

Relevance of the bioavailable fraction of DDT and its metabolites in freshwater sediment toxicity: New insight into the mode of action of these chemicals on Dictyostelium discoideum.

PubMed

Sforzini, Susanna; Governa, Daniela; Boeri, Marta; Oliveri, Laura; Oldani, Alessandro; Vago, Fabio; Viarengo, Aldo; Borrelli, Raffaella

2016-10-01

In this work, the toxicity of lake sediments contaminated with DDT and its metabolites DDD and DDE (collectively, DDX) was evaluated with widely used toxicity tests (i.e., Vibrio fischeri, Daphnia magna, Pseudokirchneriella subcapitata, and Lumbriculus variegatus) and with the social amoeba Dictyostelium discoideum, a model organism that is also suitable for studying pollutant-induced alterations at the molecular and cellular levels. Although the DDX concentration in the sediments was high (732.5 ppb), the results suggested a minimal environmental risk; in fact, no evidence of harmful effects was found using the different bioassays or when we considered the results of more sensitive sublethal biomarkers in D. discoideum amoebae. In line with the biological results, the chemical data showed that the concentration of DDX in the pore water (in general a highly bioavailable phase) showed a minimal value (0.0071ppb). To confirm the importance of the bioavailability of the toxic chemicals in determining their biological effects and to investigate the mechanisms of DDX toxicity, we exposed D. discoideum amoebae to 732.5ppb DDX in water solution. DDX had no effect on cell viability; however, a strong reduction in amoebae replication rate was observed, which depended mainly on a reduction in endocytosis rate and on lysosomal and mitochondrial alterations. In the presence of a moderate and transient increase in reactive oxygen species, the glutathione level in DDX-exposed amoebae drastically decreased. These results highlight that studies of the bioavailability of pollutants in environmental matrices and their biological effects are essential for site-specific ecological risk assessment. Moreover, glutathione depletion in DDX-exposed organisms is a new finding that could open the possibility of developing new pesticide mixtures that are more effective against DDT-resistant malaria vectors. Copyright © 2016 Elsevier Inc. All rights reserved.

Tannic acid mitigates the DMBA/croton oil-induced skin cancer progression in mice.

PubMed

Majed, Ferial; Rashid, Summya; Khan, Abdul Quaiyoom; Nafees, Sana; Ali, Nemat; Ali, Rashid; Khan, Rehan; Hasan, Syed Kazim; Mehdi, Syed Jafar; Sultana, Sarwat

2015-01-01

Skin cancer is the most common malignancy in the world and also one of the major causes of death worldwide. The toxic environmental pollutant 7,12-dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemical-induced toxicities and carcinogenesis as well. In the present study, we have evaluated the therapeutic potential of tannic acid in DMBA + croton oil-induced skin cancer in Swiss albino mice. Protective effect of TA against skin cancer was evaluated in terms of antioxidant enzymes activities, lipid peroxidation, histopathological changes and expression of inflammation and early tumour markers. DMBA + croton oil causes depletion of antioxidant enzymes (p < 0.001) and elevation of early inflammatory and tumour promotional events. TA prevents the DMBA + croton oil-induced toxicity through a protective mechanism that involves the reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of proinflammatory cytokine such as IL-6 release at a very significant level (p < 0.001). It could be concluded from our results that TA attenuates DMBA + croton oil-induced tumour promotional potential possibly by inhibiting oxidative and inflammatory responses and acts as antioxidant, anti-inflammatory and antiproliferative agent.

R-IDEAL: A Framework for Systematic Clinical Evaluation of Technical Innovations in Radiation Oncology.

PubMed

Verkooijen, Helena M; Kerkmeijer, Linda G W; Fuller, Clifton D; Huddart, Robbert; Faivre-Finn, Corinne; Verheij, Marcel; Mook, Stella; Sahgal, Arjun; Hall, Emma; Schultz, Chris

2017-01-01

The pace of innovation in radiation oncology is high and the window of opportunity for evaluation narrow. Financial incentives, industry pressure, and patients' demand for high-tech treatments have led to widespread implementation of innovations before, or even without, robust evidence of improved outcomes has been generated. The standard phase I-IV framework for drug evaluation is not the most efficient and desirable framework for assessment of technological innovations. In order to provide a standard assessment methodology for clinical evaluation of innovations in radiotherapy, we adapted the surgical IDEAL framework to fit the radiation oncology setting. Like surgery, clinical evaluation of innovations in radiation oncology is complicated by continuous technical development, team and operator dependence, and differences in quality control. Contrary to surgery, radiotherapy innovations may be used in various ways, e.g., at different tumor sites and with different aims, such as radiation volume reduction and dose escalation. Also, the effect of radiation treatment can be modeled, allowing better prediction of potential benefits and improved patient selection. Key distinctive features of R-IDEAL include the important role of predicate and modeling studies (Stage 0), randomization at an early stage in the development of the technology, and long-term follow-up for late toxicity. We implemented R-IDEAL for clinical evaluation of a recent innovation in radiation oncology, the MRI-guided linear accelerator (MR-Linac). MR-Linac combines a radiotherapy linear accelerator with a 1.5-T MRI, aiming for improved targeting, dose escalation, and margin reduction, and is expected to increase the use of hypofractionation, improve tumor control, leading to higher cure rates and less toxicity. An international consortium, with participants from seven large cancer institutes from Europe and North America, has adopted the R-IDEAL framework to work toward coordinated, evidence-based introduction of the MR-Linac. R-IDEAL holds the promise for timely, evidence-based introduction of radiotherapy innovations with proven superior effectiveness, while preventing unnecessary exposure of patients to potentially harmful interventions.

Equity and Information: Information Regulation, Environmental Justice, and Risks from Toxic Chemicals

ERIC Educational Resources Information Center

Shapiro, Marc D.

2005-01-01

Decreases over time in pounds of industrial chemical emissions have led to concerns that nonminority, higher-income communities have benefited disproportionately in reductions in risk. Toxic chemical release data, modeled for toxicity and dispersion in square kilometer units across 45 states, are used to test six sets of hypotheses of potential…

Wet air oxidation pretreatment of biomethanated distillery effluent: mapping pretreatment efficiency in terms color, toxicity reduction and biogas generation.

PubMed

Sarat Chandra, T; Malik, S N; Suvidha, G; Padmere, M L; Shanmugam, P; Mudliar, S N

2014-04-01

The effluents from molasses-based distilleries after biomethanation are beset with problems of intensified dark brown color, high residual COD, low biodegradability index (BOD/COD ratio <0.2) and toxicity issues for possible land application as a potential fertilizer. Wet air oxidation (WAO) pretreatment of biomethanated distillery effluent resulted in substantial enhancement in the biodegradability index (BI) (up to 0.8). WAO pretreated effluent on anaerobic digestion indicated favorable biogas generation with methane content up to 64% along with concomitant COD reduction up to 54.75%. The HPLC analysis indicated that the pretreatment facilitated degradation of major color containing compounds-namely melanoidins, up to 97.8%. The pretreated effluent with enhanced biodegradability along with substantially reduced color also indicated positive effect on seed germination (up to 100%), implying toxicity reduction of the effluent post WAO pretreatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Cytotoxicity of Spent Pot Liner on Allium cepa root tip cells: A comparative analysis in meristematic cell type on toxicity bioassays.

PubMed

Palmieri, Marcel José; Andrade-Vieira, Larissa Fonseca; Campos, José Marcello Salabert; Dos Santos Gedraite, Leonardo; Davide, Lisete Chamma

2016-11-01

Spent Pot Liner (SPL) is a waste generated during the production of aluminum. It is comprised of a mixture of substances most of which, like cyanide, aluminum and fluoride, are toxic. Previous studies indicate the highly toxic nature of SPL. However studies using cells of the differentiation/elongation zone of the root meristem (referred as M2 cells in this study) after a proper recovery period in water were never considered. Using these cells could be useful to further understanding the toxicity mechanisms of SPL. A comparative approach between the effects on M2 cells and meristematic cells of the proximal meristem zone (referred as M1 cells in this study) could lead to understanding how DNA damage caused by SPL behaves on successive generations of cells. Allium cepa cells were exposed to 4 different concentrations of SPL (2.5, 5, 7.5 and 10gL(-1)) mixed with soil and diluted in a CaCl2 0.01M to simulate the ionic forces naturally encountered on the environment. A solution containing only soil diluted on CaCl2 0.01M was used as control. M1 and M2 cells were evaluated separately, taking into account four different parameters: (1) mitotic alterations (MA); (2) presence of condensed nuclei (CN); (3) mitotic index (MI); (4) presence of micronucleus (MCN). Significant differences were observed between M1 and M2 roots tip cells for these four parameters accessed. M1 cells was more prompt to reveal citogenotoxicity through the higher frequency of MA observed. Meanwhile, for M2 cells higher frequencies of MCN and CN was noticed, followed by a reduction of MI. Also, it was possible to detect significant differences between the tested treatments and the control on every case. These results indicate SPL toxic effects carries on to future cells generations. This emphasizes the need to properly manage this waste. Joint evaluation of cells from both M1 and M2 regions was proven valuable for the evaluation of a series of parameters on all toxicity tests. Copyright © 2016. Published by Elsevier Inc.

Application of a novel integrated toxicity testing strategy incorporating "3R" principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor.

PubMed

Terry, Claire; Rasoulpour, Reza J; Saghir, Shakil; Marty, Sue; Gollapudi, B Bhaskar; Billington, Richard

2014-05-01

Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) ( Ellis-Hutchings et al. 2014 ); liver tumors in rodents mediated via CAR/PXR ( LeBaron et al. 2014 ); and Leydig cell tumors in Fischer 344 rats ( Rasoulpour et al. 2014 ).

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

PubMed

Giusti, M; Caorsi, V; Mortara, L; Caputo, M; Monti, E; Schiavo, M; Bagnara, M C; Minuto, F; Bagnasco, M

2014-03-01

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.

Bio-Physicochemical Interactions of Engineered Nanomaterials in in Vitro Cell Culture Model

DTIC Science & Technology

2014-10-11

are the important factors to study their toxicity . To investigate the potential role of oxidative stress as a mechanism of toxicity , reactive oxygen...of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO) lactate dehydrogenase (LDH) level and reduction in...potential role of oxidative stress as a mechanism of toxicity , reactive oxygen species (ROS), nitric oxide (NO), lactate dehydrogenase (LDH) level

Toxicity of herbicides in highway runoff.

PubMed

Huang, Xinjiang; Fong, Stephanie; Deanovic, Linda; Young, Thomas M

2005-09-01

Previous field monitoring at two highway sites found highway-applied herbicides in storm water runoff at maximum concentrations ranging from 10 microg/L for glyphosate and diuron to as high as 200 microg/L for oryzalin. To determine whether these herbicides at these concentrations can cause any toxicity to aquatic organisms, a standard toxicity study was conducted. Storm water was collected along Highway 37, Sonoma County, California, USA, and the herbicides isoxaben, oryzalin, diuron, clopyralid, and glyphosate were spiked into the storm water at the highest concentrations observed during the five previous field-monitoring campaigns. Three different toxicity studies were conducted and the results showed the following: No significant reduction in reproduction or increase in mortality relative to the control for an 8-d Ceriodaphnia (water flea) toxicity test; no significant increase in mortality or decrease in biomass compared to the control during a 7-d Pimephales (fish) toxicity test; and, in a 96-h Selenastrum (algae) toxicity test, both the 10-microg/L diuron treatment and the combined 50-microg/L isoxaben plus 200-microg/L oryzalin treatment produced significant (p < 0.05) reductions in algal growth compared to the controls, although the 30-microg/L clopyralid or 10-microg/L glyphosate treatments did not exhibit any toxic effects.

Clinical Management of HIV Drug Resistance

PubMed Central

Cortez, Karoll J.; Maldarelli, Frank

2011-01-01

Combination antiretroviral therapy for HIV-1 infection has resulted in profound reductions in viremia and is associated with marked improvements in morbidity and mortality. Therapy is not curative, however, and prolonged therapy is complicated by drug toxicity and the emergence of drug resistance. Management of clinical drug resistance requires in depth evaluation, and includes extensive history, physical examination and laboratory studies. Appropriate use of resistance testing provides valuable information useful in constructing regimens for treatment-experienced individuals with viremia during therapy. This review outlines the emergence of drug resistance in vivo, and describes clinical evaluation and therapeutic options of the individual with rebound viremia during therapy. PMID:21994737

Showcasing Sustainability in Your Toxics Release Inventory Report

EPA Pesticide Factsheets

From a June 2012 webinar, these slides contain guidance for reporting Pollution Prevention and Source Reduction data on the Toxics Release Inventory Form R and a synopsis of EPA's use of this information.

Axonal neurofilaments are nonessential elements of toxicant-induced reductions in fast axonal transport: video-enhanced differential interference microscopy in peripheral nervous system axons.

PubMed

Stone, J D; Peterson, A P; Eyer, J; Oblak, T G; Sickles, D W

1999-11-15

Neurofilament modification and accumulation, occurring in toxicant-induced neuropathies, has been proposed to compromise fast axonal transport and contribute to neurological symptoms or pathology. The current study compares the effects of the neurotoxicants acrylamide (ACR) and 2,5-hexanedione (2,5-HD) on the quantity of fast, bidirectional vesicular traffic within isolated mouse sciatic nerve axons from transgenic mice lacking axonal neurofilaments (Eyer and Peterson, Neuron 12, 1-20, 1994) and nontransgenic littermates possessing neurofilaments. Fast anterograde and retrograde membrane bound organelle (MBO) traffic was quantitated within axons, before and after toxicant exposure, using video-enhanced differential interference contrast (AVEC-DIC) microscopy. Addition of 0.7 mM ACR to the buffer bathing the nerve produced a time-dependent reduction in bidirectional transport with a similar time to onset and magnitude in both transgenic and nontransgenic mice. 2,5-HD (4 mM) exposure reduced bidirectional vesicle traffic by a similar amount in both transgenic and nontransgenic animals. The time to onset of the transport reduction was less and the magnitude of the reduction was greater with 2,5-HD compared to ACR. A single 10-min exposure to ACR or 2,5-HD produced a similar reduction in transport to that produced by prolonged (1 h) exposure. Nonneurotoxic propionamide or 3,4-hexanedione (3,4-HD) produced no changes in bidirectional transport in either transgenic or nontransgenic animals. We conclude that ACR or 2,5-HD produces a rapid, saturable, nonreversible, neurotoxicant-specific reduction in fast bidirectional transport within isolated peripheral nerve axons. These actions are mediated through direct modification of axonal component(s), which are independent of toxicant-induced modifications of, or accumulations of, neurofilaments. Copyright 1999 Academic Press.

Determination of thiaarenes and polycyclic aromatic hydrocarbons in workplace air of an aluminum reduction plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becker, G.; Colmsjoe, A.; Oestman, C.

1999-05-01

Quantitation of a variety of tetra-, penta-, and hexacyclic aromatic sulfur heterocycles (thiaarenes) in workplace air of an aluminum reduction plant has been made by help of gas chromatography with atomic emission detection (GC-AED). Personal exposure to those thiaarenes and to polycyclic aromatic hydrocarbons depending on work categories has been evaluated. Summarized concentrations of the thiaarenes investigated have been found to be 0.4--19.0 {micro}g/m{sup 3}. When using sulfur selective AED, samples could be analyzed without a prior separation of the thiaarenes from the PAH. The present data indicate a contribution of thiaarenes to the overall toxicity of coal tar pitchmore » volatiles in this work environment.« less

Setup Variations in Radiotherapy of Anal Cancer: Advantages of Target Volume Reduction Using Image-Guided Radiation Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Yijen, E-mail: yichen@coh.org; Suh, Steve; Nelson, Rebecca A.

2012-09-01

Purpose: To define setup variations in the radiation treatment (RT) of anal cancer and to report the advantages of image-guided RT (IGRT) in terms of reduction of target volume and treatment-related side effects. Methods and Materials: Twelve consecutive patients with anal cancer treated by combined chemoradiation by use of helical tomotherapy from March 2007 to November 2008 were selected. With patients immobilized and positioned in place, megavoltage computed tomography (MVCT) scans were performed before each treatment and were automatically registered to planning CT scans. Patients were shifted per the registration data and treated. A total of 365 MVCT scans weremore » analyzed. The primary site received a median dose of 55 Gy. To evaluate the potential dosimetric advantage(s) of IGRT, cases were replanned according to Radiation Therapy Oncology Group 0529, with and without adding recommended setup variations from the current study. Results: Significant setup variations were observed throughout the course of RT. The standard deviations for systematic setup correction in the anterior-posterior (AP), lateral, and superior-inferior (SI) directions and roll rotation were 1.1, 3.6, and 3.2 mm, and 0.3 Degree-Sign , respectively. The average random setup variations were 3.8, 5.5, and 2.9 mm, and 0.5 Degree-Sign , respectively. Without daily IGRT, margins of 4.9, 11.1, and 8.5 mm in the AP, lateral, and SI directions would have been needed to ensure that the planning target volume (PTV) received {>=}95% of the prescribed dose. Conversely, daily IGRT required no extra margins on PTV and resulted in a significant reduction of V15 and V45 of intestine and V10 of pelvic bone marrow. Favorable toxicities were observed, except for acute hematologic toxicity. Conclusions: Daily MVCT scans before each treatment can effectively detect setup variations and thereby reduce PTV margins in the treatment of anal cancer. The use of concurrent chemotherapy and IGRT provided favorable toxicities, except for acute hematologic toxicity.« less

Variations in toxicity of semi-coking wastewater treatment processes and their toxicity prediction.

PubMed

Ma, Xiaoyan; Wang, Xiaochang; Liu, Yongjun; Gao, Jian; Wang, Yongkun

2017-04-01

Chemical analyses and bioassays using Vibrio fischeri and Daphnia magna were conducted to evaluate comprehensively the variation of biotoxicity caused by contaminants in wastewater from a semi-coking wastewater treatment plant (WWTP). Pretreatment units (including an oil-water separator, a phenols extraction tower, an ammonia stripping tower, and a regulation tank) followed by treatment units (including anaerobic-oxic treatment units, coagulation-sedimentation treatment units, and an active carbon adsorption column) were employed in the semi-coking WWTP. Five benzenes, 11 phenols, and five polycyclic aromatic hydrocarbons (PAHs) were investigated as the dominant contaminants in semi-coking wastewater. Because of residual extractant, the phenols extraction process increased acute toxicity to V. fischeri and immobilization and lethal toxicity to D. magna. The acute toxicity of pretreated wastewater to V. fischeri was still higher than that of raw semi-coking wastewater, even though 90.0% of benzenes, 94.8% of phenols, and 81.0% of PAHs were removed. After wastewater pretreatment, phenols and PAHs were mainly removed by anaerobic-oxic and coagulation-sedimentation treatment processes respectively, and a subsequent active carbon adsorption process further reduced the concentrations of all target chemicals to below detection limits. An effective biotoxicity reduction was found during the coagulation-sedimentation and active carbon adsorption treatment processes. The concentration addition model can be applied for toxicity prediction of wastewater from the semi-coking WWTP. The deviation between the measured and predicted toxicity results may result from the effects of compounds not detectable by instrumental analyses, the synergistic effect of detected contaminants, or possible transformation products. Copyright © 2016. Published by Elsevier Inc.

Biotoxicity assessment and toxicity mechanism on coal gasification wastewater (CGW): A comparative analysis of effluent from different treatment processes.

PubMed

Ma, Weiwei; Han, Yuxing; Xu, Chunyan; Han, Hongjun; Zhu, Hao; Li, Kun; Zheng, Mengqi

2018-05-04

Even though coal gasification wastewater (CGW) treated by various biochemical treatment processes generally met the national discharge standard, its potential biotoxicity was still unknown. Therefore, in this study, bioassay with Tetrahymena thermophila (T. thermophila) was conducted to comprehensively evaluate the variation of biotoxicity in raw CGW and the treated effluent from lab-scale micro-electrolysis integrated with biological reactor (MEBR), single iron-carbon micro-electrolysis (ICME) and conventional activated sludge (CAS) processes. The results illustrated that raw CGW presented intensive acute toxicity with 24 h EC 50 value of 8.401% and toxic unit (TU) value of 11.90. Moreover, it performed significant cell membrane destruction and DNA damage even at 10% dilution concentration. The toxicant identification results revealed that multiple toxic polar compounds such as phenolic, heterocyclic and polycyclic aromatic compounds were the main contributors for biotoxicity. Furthermore, these compounds could accelerate oxidative stress, thereby inducing oxidative damage of cell membrane and DNA. As for treated effluent, TU value was decreased by 90.58% in MEBR process. An effective biotoxicity reduction was achieved in MEBR process owing to high removal efficiency in polar organic toxicants. In contrast, effluent from ICME and CAS processes presented relatively high acute toxicity and genotoxicity, because various heterocyclic and polycyclic aromatic compounds were difficult to be degraded in these processes. Therefore, it was suggested that MEBR was a potential and feasible process for improving CGW treatment and minimizing ecological risk. Copyright © 2018. Published by Elsevier B.V.

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone

PubMed Central

O'Sullivan, J M; McCready, V R; Flux, G; Norman, A R; Buffa, F M; Chittenden, S; Guy, M; Pomeroy, K; Cook, G; Gadd, J; Treleaven, J; Al-Deen, A; Horwich, A; Huddart, R A; Dearnaley, D P

2002-01-01

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates. British Journal of Cancer (2002) 86, 1715–1720. doi:10.1038/sj.bjc.6600348 www.bjcancer.com © 2002 Cancer Research UK PMID:12087455

Degradation of Diuron by Phanerochaete chrysosporium: Role of Ligninolytic Enzymes and Cytochrome P450

PubMed Central

Coelho-Moreira, Jaqueline da Silva; de Souza, Aline Cristine da Silva; Oliveira, Roselene Ferreira; de Sá-Nakanishi, Anacharis Babeto; de Souza, Cristina Giatti Marques; Peralta, Rosane Marina

2013-01-01

The white-rot fungus Phanerochaete chrysosporium was investigated for its capacity to degrade the herbicide diuron in liquid stationary cultures. The presence of diuron increased the production of lignin peroxidase in relation to control cultures but only barely affected the production of manganese peroxidase. The herbicide at the concentration of 7 μg/mL did not cause any reduction in the biomass production and it was almost completely removed after 10 days. Concomitantly with the removal of diuron, two metabolites, DCPMU [1-(3,4-dichlorophenyl)-3-methylurea] and DCPU [(3,4-dichlorophenyl)urea], were detected in the culture medium at the concentrations of 0.74 μg/mL and 0.06 μg/mL, respectively. Crude extracellular ligninolytic enzymes were not efficient in the in vitro degradation of diuron. In addition, 1-aminobenzotriazole (ABT), a cytochrome P450 inhibitor, significantly inhibited both diuron degradation and metabolites production. Significant reduction in the toxicity evaluated by the Lactuca sativa L. bioassay was observed in the cultures after 10 days of cultivation. In conclusion, P. chrysosporium can efficiently metabolize diuron without the accumulation of toxic products. PMID:24490150

LuminoTox as a tool to optimize ozone doses for the removal of contaminants and their associated toxicity.

PubMed

Marshall, Meghan; Yargeau, Viviane

2018-03-01

New treatment technologies and quality monitoring tools are needed for Contaminants of Emerging Concern (CECs) in wastewater. The purpose of this work was to assess the LuminoTox as a monitoring tool for CEC-associated toxicity in municipal wastewater during ozone treatment, and to evaluate the impact of different ozone feed concentrations at equivalent ozone doses for removing toxicity. The LuminoTox was sensitive at monitoring changes in toxicity of atrazine (ATZ) in synthetic wastewater (SWW) and in a 14 CECs mix in secondary effluent (SE) during ozone treatment. In both experiments, a decrease in toxicity was observed with increasing transferred ozone dose, which corresponded to a decrease in CEC concentration. For ATZ in SWW, a 5 ppm ozone feed showed better toxicity removal, up to 25% and 35% inhibition for LuminoTox algae biosensors SAPS I and SAPS II, respectively, for statistically equivalent ozone dose pairs of 43 mg (5 ppm ozone feed) and 36 mg (15 ppm ozone feed). The opposite was true for the 14 CECs in SE; the 15 ppm ozone feed showed better toxicity removal, up to a reduction of 37% and 40% for SAPS I and SAPS II inhibition, respectively, for statistically equivalent ozone dose pairs of 42 mg (5 ppm ozone feed) and 42 mg (15 ppm ozone feed). Different feed applications had an impact on the efficiency of toxicity removal for equivalent ozone doses; this efficiency appears to depend on the type of contaminants and/or wastewater matrix. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cerium dioxide (CeO2) nanoparticles decrease arsenite (As(III)) cytotoxicity to 16HBE14o- human bronchial epithelial cells.

PubMed

Zeng, Chao; Nguyen, Chi; Boitano, Scott; Field, Jim A; Shadman, Farhang; Sierra-Alvarez, Reyes

2018-07-01

The production and application of engineered nanoparticles (NPs) are increasing in demand with the rapid development of nanotechnology. However, there are concerns that some of these novel materials could lead to emerging environmental and health problems. Some NPs are able to facilitate the transport of contaminants into cells/organisms via a "Trojan Horse" effect which enhances the toxicity of the adsorbed materials. In this work, we evaluated the toxicity of arsenite (As(III)) adsorbed onto cerium dioxide (CeO 2 ) NPs to human bronchial epithelial cells (16HBE14o-) using the xCELLigence real time cell analyzing system (RTCA). Application of 0.5 mg/L As(III) resulted in 81.3% reduction of cell index (CI, an RTCA measure of cell toxicity) over 48 h when compared to control cells exposed to medium lacking As(III). However, when the cells were exposed to 0.5 mg/L As(III) in the presence of CeO 2 NPs (250 mg/L), the CI was only reduced by 12.9% compared to the control. The CeO 2 NPs had a high capacity for As(III) adsorption (20.2 mg/g CeO 2 ) in the bioassay medium, effectively reducing dissolved As(III) in the aqueous solution and resulting in reduced toxicity. Transmission electron microscopy was used to study the transport of CeO 2 NPs into 16HBE14o- cells. NP uptake via engulfment was observed and the internalized NPs accumulated in vesicles. The results demonstrate that dissolved As(III) in the aqueous solution was the decisive factor controlling As(III) toxicity of 16HBE14o- cells, and that CeO 2 NPs effectively reduced available As(III) through adsorption. These data emphasize the evaluation of mixtures when assaying toxicity. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of low-level copper and pentachlorophenol exposure on various early life stages of Xenopus laevis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fort, D.J.; Stover, E.L.

1996-12-31

An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis, was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorphenol, from 0 d to 4 d (standard Frog Embryo Teratogenesis Assay--Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased in eachmore » successive time period. Longer-term exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5 {micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

Effect of chronic copper and pentachlorophenol exposure to early life stages of Xenopus laevis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fort, D.J.; Stover, E.L.

1995-12-31

An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorophenol, from 0 d to 4 d (standard Frog Embryo Teratagenesis Assay Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased inmore » each successive time period. Continuous exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5/{micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

Mitoxantrone is More Toxic than Doxorubicin in SH-SY5Y Human Cells: A 'Chemobrain' In Vitro Study.

PubMed

Almeida, Daniela; Pinho, Rita; Correia, Verónica; Soares, Jorge; Bastos, Maria de Lourdes; Carvalho, Félix; Capela, João Paulo; Costa, Vera Marisa

2018-05-05

The potential neurotoxic effects of anticancer drugs, like doxorubicin (DOX) and mitoxantrone (MTX; also used in multiple sclerosis), are presently important reasons for concern, following epidemiological data indicating that cancer survivors submitted to chemotherapy may suffer cognitive deficits. We evaluated the in vitro neurotoxicity of two commonly used chemotherapeutic drugs, DOX and MTX, and study their underlying mechanisms in the SH-SY5Y human neuronal cell model. Undifferentiated human SH-SY5Y cells were exposed to DOX or MTX (0.13, 0.2 and 0.5 μM) for 48 h and two cytotoxicity assays were performed, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction and the neutral red (NR) incorporation assays. Phase contrast microphotographs, Hoechst, and acridine orange/ethidium bromide stains were performed. Mitochondrial membrane potential was also assessed. Moreover, putative protective drugs, namely the antioxidants N -acetyl-l-cysteine (NAC; 1 mM) and 100 μM tiron, the inhibitor of caspase-3/7, Ac-DEVD-CHO (100 μM), and a protein synthesis inhibitor, cycloheximide (CHX; 10 nM), were tested to prevent DOX- or MTX-induced toxicity. The MTT reduction assay was also done in differentiated SH-SY5Y cells following exposure to 0.2 μM DOX or MTX. MTX was more toxic than DOX in both cytotoxicity assays and according to the morphological analyses. MTX also evoked a higher number of apoptotic nuclei than DOX. Both drugs, at the 0.13 μM concentration, caused mitochondrial membrane potential depolarization after a 48-h exposure. Regarding the putative neuroprotectors, 1 mM NAC was not able to prevent the cytotoxicity caused by either drug. Notwithstanding, 100 μM tiron was capable of partially reverting MTX-induced cytotoxicity in the NR uptake assay. One hundred μM Ac-DEVD-CHO and 10 nM cycloheximide (CHX) also partially prevented the toxicity induced by DOX in the NR uptake assay. MTX was more toxic than DOX in differentiated SH-SY5Y cells, while MTX had similar toxicity in differentiated and undifferentiated SH-SY5Y cells. In fact, MTX was the most neurotoxic drug tested and the mechanisms involved seem dissimilar among drugs. Thus, its toxicity mechanisms need to be further investigated as to determine the putative neurotoxicity for multiple sclerosis and cancer patients.

Biochemical characterization of ethanol-dependent reduction of furfural by alcohol dehydrogenases.

PubMed

Li, Qunrui; Metthew Lam, L K; Xun, Luying

2011-11-01

Lignocellulosic biomass is usually converted to hydrolysates, which consist of sugars and sugar derivatives, such as furfural. Before yeast ferments sugars to ethanol, it reduces toxic furfural to non-inhibitory furfuryl alcohol in a prolonged lag phase. Bioreduction of furfural may shorten the lag phase. Cupriavidus necator JMP134 rapidly reduces furfural with a Zn-dependent alcohol dehydrogenase (FurX) at the expense of ethanol (Li et al. 2011). The mechanism of the ethanol-dependent reduction of furfural by FurX and three homologous alcohol dehydrogenases was investigated. The reduction consisted of two individual reactions: ethanol-dependent reduction of NAD(+) to NADH and then NADH-dependent reduction of furfural to furfuryl alcohol. The kinetic parameters of the coupled reaction and the individual reactions were determined for the four enzymes. The data indicated that limited NADH was released in the coupled reaction. The enzymes had high affinities for NADH (e.g., K ( d ) of 0.043 μM for the FurX-NADH complex) and relatively low affinities for NAD(+) (e.g., K ( d ) of 87 μM for FurX-NAD(+)). The kinetic data suggest that the four enzymes are efficient "furfural reductases" with either ethanol or NADH as the reducing power. The standard free energy change (ΔG°') for ethanol-dependent reduction of furfural was determined to be -1.1 kJ mol(-1). The physiological benefit for ethanol-dependent reduction of furfural is likely to replace toxic and recalcitrant furfural with less toxic and more biodegradable acetaldehyde.

A Phase 2 Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI#6366)

PubMed Central

Carvajal, Richard D.; Tse, Archie; Shah, Manish A.; Lefkowitz, Robert A.; Gonen, Mithat; Gilman-Rosen, Lisa; Kortmansky, Jeremy; Kelsen, David P.; Schwartz, Gary K.; O'Reilly, Eileen M.

2014-01-01

Background/Aims Pancreatic adenocarcinoma (PC) harbors frequent alterations of p16, resulting in cell cycle dysregulation. A phase I study of docetaxel and flavopiridol, a pan-cyclin dependent kinase inhibitor, demonstrated encouraging clinical activity in PC. This phase II study was designed to further define the efficacy and toxicity of this regimen in patients with previously treated PC. Methods Patients with gemcitabine-refractory, metastatic PC were treated with docetaxel 35 mg/m2 followed by flavopiridol 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Tumor measurements were performed every two cycles. A Simon two-stage design was used to evaluate the primary endpoint of response. Results Ten patients were enrolled; nine were evaluable for response. No objective responses were observed; however, three patients (33%) achieved transient stable disease, with one of these patients achieving a 20% reduction in tumor size. Median survival was 4.2 months, with no patients alive at the time of analysis. Adverse events were significant, with seven patients (78%) requiring ≥1 dose reduction for transaminitis (11%), grade 4 neutropenia (33%), grade 3 fatigue (44%), and grade 3 diarrhea (22%) Conclusions The combination of flavopiridol and docetaxel has minimal activity and significant toxicity in this patient population. These results reflect the challenges of treating patients with PC in a second-line setting where the risk/benefit equation is tightly balanced. PMID:19451750

Mature landfill leachate treatment by coagulation/flocculation combined with Fenton and solar photo-Fenton processes.

PubMed

Amor, Carlos; De Torres-Socías, Estefanía; Peres, José A; Maldonado, Manuel I; Oller, Isabel; Malato, Sixto; Lucas, Marco S

2015-04-09

This work reports the treatment of a mature landfill leachate through the application of chemical-based treatment processes in order to achieve the discharge legal limits into natural water courses. Firstly, the effect of coagulation/flocculation with different chemicals was studied, evaluating the role of different initial pH and chemicals concentration. Afterwards, the efficiency of two different advanced oxidation processes for leachate remediation was assessed. Fenton and solar photo-Fenton processes were applied alone and in combination with a coagulation/flocculation pre-treatment. This physicochemical conditioning step, with 2 g L(-1) of FeCl3 · 6H2O at pH 5, allowed removing 63% of COD, 80% of turbidity and 74% of total polyphenols. Combining the coagulation/flocculation pre-treatment with Fenton reagent, it was possible to reach 89% of COD removal in 96 h. Moreover, coagulation/flocculation combined with solar photo-Fenton revealed higher DOC (75%) reductions than single solar photo-Fenton (54%). In the combined treatment (coagulation/flocculation and solar photo-Fenton), it was reached a DOC reduction of 50% after the chemical oxidation, with 110 kJ L(-1) of accumulated UV energy and a H2O2 consumption of 116 mM. Toxicity and biodegradability assays were performed to evaluate possible variations along the oxidation processes. After the combined treatment, the leachate under study presented non-toxicity but biodegradability increased. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of methanol leaf extract of Dalbergia saxatilis Hook.f (fabaceae) on renal function.

PubMed

Hassan, Fatima Ismail; Abdulkadir Umar, Zezi; Umar Habib, Danmalam; Abdullahi Hamza, Yaro

2016-01-01

Dalbegia saxatilis ( D.saxatilis ) is used as a decoction in traditional medicine for ailments such as cough, small pox, skin lesions, bronchial ailments and toothache. This study is aimed at evaluating the toxic effect of methanol leaf extract of D.saxatilis on renal function. Wistar rats of both sexes were divided into four groups of five: control animals (group 1) received distilled water 1 ml/kg while groups 2, 3 and 4 were given graded doses of the extract (250, 500 and 1000 mg/kg body weight, respectively) daily for 28 days. Body weight changes were estimated by weighing the rats twice weekly using digital weighing balance. After 28 days, blood samples were obtained for evaluation of renal indices and the kidney was used for histopathology. Data were analysed using one-way and repeated measures ANOVA using SPSS version 20. Significant weight increase in all groups were observed (p<0.05). Significant reduction in electrolytes concentration was observed following treatment with extract (250 and 500 mg/kg) (p<0.05). Histopathological findings of the kidney revealed massive necrosis of the glomerulus with tubular distortion and lymphocyte hyperplasia at 250 and 500 mg/kg while intense glomerular and tubular necrosis was observed at 1000 mg/kg of the extract. Since different doses of the extract caused reduction in electrolyte concentration and damage to the kidney it is suggested that prolonged administration of the extract is associated with increased risk of kidney toxicity .

Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers.

PubMed

Cobb, C O; Weaver, M F; Eissenberg, T

2010-10-01

Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific's Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers. 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly. Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products. While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers.

A systematic study on photocatalysis of antipyrine: Catalyst characterization, parameter optimization, reaction mechanism a toxicity evolution to plankton.

PubMed

Gong, Han; Chu, Wei; Chen, Meijuan; Wang, Qinxing

2017-04-01

The toxicity of antipyrine (AP) in the photodegradation using UV/CoFe 2 O 4 /TiO 2 was investigated by analyzing the characteristic of the catalyst, the effect of parameters (light source wavelength, catalyst dose, pH and initial AP concentration), the reaction mechanism (the organic intermediates, TOC reduction and inorganic ions release) and the newly proposed low-dosage-high-effective radical reaction approach. The catalyst shows the optimal removal efficiency under the conditions of wavelength at 350 nm, the catalyst dose at 0.5 g/L, and pH value at 5.5. Ten organic intermediates were identified, and five of them were newly reported in AP treatment process. Hydroxylation, demethylation and the cleavage of the pentacyclic ring were included in the decomposition pathways. The ring opening was certified by the 45% TOC reduction and 60% ammonia release during the process. The parent compound AP and its degradation products show positive effects on the growth of the algae. However, acute toxicity of AP was detected on brine shrimps Artemia salina. The toxicity was eliminated gradually with the decomposition of AP and the generation of the byproducts. The results indicate that the photocatalysis process is effective in AP removal, TOC reduction and toxicity elimination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Niagara River Toxics Management Plan

EPA Pesticide Factsheets

This 2007 Progress Report of the Niagara River Toxics Management Plan (NRTMP) summarizes progress made by the four parties in dealing with the 18 “Priority Toxics” through reductions in point and non-point sources to the Niagara River.

Evaluation of TCDD biodegradability under different redox conditions.

PubMed

Kao, C M; Chen, S C; Liu, J K; Wu, M J

2001-09-01

Polychlorinated dibenzo-p-dioxins have been generated as unwanted by-products in many industrial processes. Although their widespread distribution in different environmental compartments has been recognized, little is known about their fate in the ultimate environment sinks. The highly stable dioxin isomer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been called the most toxic compound known to man. In this laboratory microcosm study, TCDD bioavailability was evaluated under five reduction/oxidation (redox) conditions including aerobic biodegradation, aerobic cometabolism, methanogenesis, iron reduction, and reductive dechlorination. Activated sludge and aquifer sediments from a TCDD and a pentachlorophenol (PCP) contaminated site were used as the inocula. Acetate, sludge cake, and cane molasses were used as the primary substrates (carbon sources) in cometabolism and reductive dechlorination microcosms. After a 90-day incubation period, microcosms constructed under reductive dechlorination conditions were the only treatment showing promising remediation results. The highest TCDD degradation rate [up to 86% of TCDD removal (with an initial concentration of 96 microg/kg of soil)] was observed in the microcosms with anaerobic activated sludge as the microbial inocula and sludge cakes as the primary substrates. Except for reductive dechlorination microcosms, no significant TCDD removal was observed in the microcosms prepared under other conditions. Thus, application of an effective primary substrate to enhance the reductive dechlorination process is a feasible method for TCDD bioremediation. Bioremediation expense can be significantly reduced by the supplement of some less expensive alternative substrates (e.g., sludge cakes, cane molasses). Results would be useful in designing a scale-up in situ or on-site bioremediation system such as bioslurry reactor for field application.

The effect of changes in the USF/NASA toxicity screening test method on data from some cellular polymers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Miller, C. M.

1976-01-01

Rankings of relative toxicity can be markedly affected by changes in test variables. Revision of the USF/NASA toxicity screening test procedure to eliminate the connecting tube and supporting floor and incorporate a 1.0 g sample weight, 200 C starting temperature, and 800 C upper limit temperature for pyrolysis, reversed the rankings of flexible polyurethane and polychloroprene foams, not only in relation to each other, but also in relation to cotton and red oak. Much of the change is attributed to reduction of the distance between the sample and the test animals, and reduction of the sample weight charged. Elimination of the connecting tube increased the relative toxicity of the polyurethane foams. The materials tested were flexible polyurethane foam, without and with fire retardant; rigid polyurethane foam with fire retardant; flexible polychloroprene foam; cotton, Douglas fir, red oak, hemlock, hardboard, particle board, polystyrene, and polymethyl methacrylate.

Evaluation of the anti-mycobacterium tuberculosis activity and in vivo acute toxicity of Annona sylvatic

PubMed Central

2014-01-01

Background The recent emergence of extensively multidrug-resistant Mycobacterium tuberculosis strains has further complicated the control of tuberculosis. There is an urgent need for the development of new molecular candidates antitubercular drugs. Medicinal plants have been an excellent source of leads for the development of drugs. The aim of this study was to evaluate the in vitro activity of 28 alcoholic extracts and essential oils of native and exotic Brazilian plants against Mycobacterium tuberculosis and to further study these extracts through chemical fractionation, the isolation of their constituents, and an evaluation of the in vivo acute toxicity of the active extracts. To the best of our knowledge this is the first chemical characterization, antituberculosis activity and acute toxicity evaluation of Annona sylvatica. Methods The anti-mycobacterial activity of these extracts and their constituent compounds was evaluated using the resazurin reduction microtiter assay (REMA). To investigate the acute toxicity of these extracts in vivo, female Swiss mice were treated with the extracts at doses of 500, 1000 and 2000 mg · kg-1 of body weight. The extracts were characterized by LC-MS, and the constituents were isolated and identified by chromatographic analysis of spectroscopic data. Results Of the 28 extracts, the methanol extract obtained from the leaves of Annona sylvatica showed anti-mycobacterial activity with an minimal inhibitory concentration (MIC) of 184.33 μg/mL, and the ethyl acetate fraction (EAF) resulting from liquid-liquid partitioning of the A. sylvatica extract showed an MIC of 115.2 μg/mL. The characterization of this extract by LC-MS identified flavonoids and acetogenins as its main constituents. The phytochemical study of the A. sylvatica EAF resulted in the isolation of quercetin, luteolin, and almunequin. Conclusions Among the compounds isolated from the EAF, luteolin and almunequin were the most promising, with MICs of 236.8 μg/mL (827.28 μM) and 209.9 μg/mL (328.48 μM), respectively. The acute administration of the EAF fraction in doses of 500, 1000, and 2000 mg · kg-1 of body weight did not cause signs of toxicity in the treated animals. PMID:24974069

Evaluation of protease resistance and toxicity of amyloid-like food fibrils from whey, soy, kidney bean, and egg white.

PubMed

Lassé, Moritz; Ulluwishewa, Dulantha; Healy, Jackie; Thompson, Dion; Miller, Antonia; Roy, Nicole; Chitcholtan, Kenny; Gerrard, Juliet A

2016-02-01

The structural properties of amyloid fibrils combined with their highly functional surface chemistry make them an attractive new food ingredient, for example as highly effective gelling agents. However, the toxic role of amyloid fibrils in disease may cause some concern about their food safety because it has not been established unequivocally if consumption of food fibrils poses a health risk to consumers. Here we present a study of amyloid-like fibrils from whey, kidney bean, soy bean, and egg white to partially address this concern. Fibrils showed varied resistance to proteolytic digestion in vitro by either Proteinase K, pepsin or pancreatin. The toxicity of mature fibrils was measured in vitro and compared to native protein, early-stage-fibrillar protein, and sonicated fibrils in two immortalised human cancer cell lines, Caco-2 and Hec-1a. There was no reduction in the viability of either Caco-2 or Hec-1a cells after treatment with a fibril concentration of up to 0.25 mg/mL. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ketoconazole-induced testicular damage in rats reduced by Gentiana extract.

PubMed

Amin, Amr

2008-04-01

Ketoconazole (KET) is an antifungal drug with a broad spectrum of activity that also induces reproductive toxicity in humans and animals. The protective effect of Gentiana (GEN) extract (Gentiana lutea) against KET-induced testicular damage was evaluated in male Wistar rats. GEN extract was administered orally (1g/kgbwt/day) for 26 days. Three weeks after extract administration, KET was co-administered intraperitoneally at a dose of 100mg/kg once a day for 5 days. KET-induced reproductive toxicity was associated with clear reductions of the weights of testes and epididymides, sperm indices and serum testosterone levels. KET also induced severe testicular histopathological lesions such as degeneration of the seminiferous tubules and depletion of germ cells. In addition, marked oxidative damage to testicular lipids and alterations of natural antioxidants (catalase (CAT) and superoxide dismutase (SOD)) were reported in association with KET toxicity. Most of the KET-induced effects were greatly decreased with the concomitant application of GEN extract. This study suggests a protective role of GEN extract that could be attributed to its antioxidant properties.

Amelioration of ethionine toxicity in the chick.

PubMed

Lowry, K R; Baker, D H

1987-06-01

Several chick bioassays were conducted to evaluate means of ameliorating ethionine toxicity. Supplementing a corn-soy diet marginally deficient in sulfur amino acids (methionine + cystine) with .075% D,L-ethionine reduced weight gain in 8-day-old chicks by 70% compared to gains of unsupplemented controls. Dietary addition of .50% DL-methionine prevented reduction in weight gain and feed intake resulting from ethionine supplementation whereas feeding supplemental L-cystine was without effect. Supplementation of the ethionine-containing diet with either choline or betaine ameliorated the growth depression, although neither compound was able to completely overcome the toxic effects of ethionine. Dietary ethionine did not affect plasma levels of free methionine or cystine but did increase plasma free glycine 6-fold. Dietary addition of .50% DL-methionine caused normalization of plasma glycine levels whereas it elevated plasma methionine concentration. Although results suggested the possibility of ethionine-induced serine or threonine deficiency, dietary additions of .75% L-serine or .75% L-threonine failed to improve chick weight gain. These studies suggest that ethionine, in addition to affecting transsulfuration and transmethylation activity may exert specific effects on certain amino acids in tissue pools.

Light-activated phenalen-1-one bactericides: efficacy, toxicity and mechanism compared with benzalkonium chloride.

PubMed

Muehler, Denise; Sommer, Kerstin; Wennige, Sara; Hiller, Karl-Anton; Cieplik, Fabian; Maisch, Tim; Späth, Andreas

2017-11-01

Five photoactive compounds with variable elongated alkyl-substituents in a phenalen-1-one structure were examined in view of structural similarity to the antimicrobial agent benzalkonium chloride (BAC). All phenalen-1-ones and BAC were evaluated for their antimicrobial properties against Staphylococcus aureus, methicillin-resistant S. aureus, Escherichia coli, Pseudomonas aeruginosa and for their eukaryotic toxicity against normal human epidermal keratinocyte (NHEK) cells to narrow down the BAC-like effect and the photodynamic effect depending on the chemical structure. All compounds were investigated for effective concentration ranges, where a bacterial reduction of 5 log 10 is achieved, while an NHEK survival of 80% is ensured. Effective concentration ranges were found for four out of five photoactive compounds, but not for BAC and the compound with BAC-like alkyl chain length. Chain length size and polar area of the respective head-groups of phenalen-1-one compounds or BAC showed an influence on the incorporation inside lipid membranes and thus, head-groups may have an impact on the toxicity of antimicrobials.

Effect of co-application of nano-zero valent iron and biochar on the total and freely dissolved polycyclic aromatic hydrocarbons removal and toxicity of contaminated soils.

PubMed

Oleszczuk, Patryk; Kołtowski, Michał

2017-02-01

The aim of this study was to investigate co-application of biochar and nano zero-valent iron (nZVI) in order to increase the degradation of PAHs and reduce the toxicity of soils historically contaminated with these compounds. To performed the experiment biochar, biochar with nZVI (2 g kg -1 or 10 g kg -1 soil), or nZVI alone (2 g kg -1 or 10 g kg -1 soil) were added to the PAHs contaminated soils. The soils alone and soils with amendments were aged by mixing for 7 and 30 days. After that the chemical analysis were carried out and total (C tot ) and C free PAH content in the samples were determined. Moreover, the toxicity of aqueous extracts were investigated using the Microtox ® (Vibrio fischeri) method. Results showed that any of used nZVI dose did not reduce the content of C tot or C free PAHs in contaminated soils, but biochar applied both alone and together with the nZVI significantly reduced C tot and C free PAHs. However, no significant differences in PAH reduction were found between biochar alone and biochar with nZVI addition. This indicates that the observed reduction was mostly associated with the sorption properties of biochar. Moreover, only in the case of co-application of biochar and nZVI reduction of the toxicity of nZVI to V. fischeri was observed. The toxic effect was different and depend on the type of soil and their properties including total organic carbon and black carbon content, which may affect the PAHs reduction efficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models

PubMed Central

Lamas, DJMartinel; Nicoud, MB; Sterle, HA; Carabajal, E; Tesan, F; Perazzo, JC; Cremaschi, GA; Rivera, ES; Medina, VA

2015-01-01

The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice. PMID:27551485

Antiulcerogenic activity of Carica papaya seed in rats.

PubMed

Pinto, Lorraine Aparecida; Cordeiro, Kátia Wolff; Carrasco, Viviane; Carollo, Carlos Alexandre; Cardoso, Cláudia Andréa Lima; Argadoña, Eliana Janet Sanjinez; Freitas, Karine de Cássia

2015-03-01

The purpose of the present study was to evaluate the gastroprotective and healing effects of the methanolic extract of the seed of the papaya Carica papaya L. (MECP) in rats. Models of acute gastric ulcer induction by ethanol and indomethacin and of chronic ulcer by acetic acid were used. The gastric juice and mucus parameters were evaluated using the pylorus ligation model, and the involvement of sulfhydryl compounds (GSH) and nitric oxide in the gastroprotective effect was analyzed using the ethanol model. The toxicity was assessed through toxicity tests. No signs of toxicity were observed when the rats received a single dose of 2000 mg/kg of extract. The MECP in doses of 125, 250, and 500 mg/kg significantly reduced the gastric lesion with 56, 76, and 82 % inhibition, respectively, and a dose of 30 mg/kg lansoprazole showed 79 % inhibition in the ethanol model. MECP (125, 250, 500 mg/kg) and cimetidine (200 mg/kg) reduced the gastric lesion in the indomethacin model, with 62, 67, 81, and 85 % inhibition, respectively. The MECP (500 mg/kg) and cimetidine (200 mg/kg) treatments showed a reduction in ulcerative symptoms induced by acetic acid by 84 and 73 %, respectively. The antiulcerogenic activity seems to involve GSH because the inhibition dropped from 72 to 13 % in the presence of a GSH inhibitor. Moreover, the MECP showed systemic action, increasing the mucus production and decreasing gastric acidity. Treatments with MECP induce gastroprotection without signs of toxicity. This effect seems to involve sulfhydryl compounds, increased mucus, and reduced gastric acidity.

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study

USDA-ARS?s Scientific Manuscript database

Background: The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not l...

Radiotherapy in Prostate Cancer Patients With Pelvic Lymphocele After Surgery: Clinical and Dosimetric Data of 30 Patients.

PubMed

Jereczek-Fossa, Barbara Alicja; Colangione, Sarah Pia; Fodor, Cristiana; Russo, Stefania; Cambria, Raffaella; Zerini, Dario; Bonora, Maria; Cecconi, Agnese; Vischioni, Barbara; Vavassori, Andrea; Matei, Deliu Victor; Bottero, Danilo; Brescia, Antonio; Musi, Gennaro; Mazzoleni, Federica; Orsi, Franco; Bonomo, Guido; De Cobelli, Ottavio; Orecchia, Roberto

2015-08-01

The purpose of the study was to evaluate the feasibility of irradiation after prostatectomy in the presence of asymptomatic pelvic lymphocele. The inclusion criteria for this study were: (1) patients referred for postoperative (adjuvant or salvage) intensity modulated radiotherapy (IMRT; 66-69 Gy in 30 fractions); (2) detection of postoperative pelvic lymphocele at the simulation computed tomography [CT] scan; (3) no clinical symptoms; and (4) written informed consent. Radiotherapy toxicity and occurrence of symptoms or complications of lymphocele were analyzed. Dosimetric data (IMRT plans) and the modification of lymphocele volume during radiotherapy (cone beam CT [CBCT] scan) were evaluated. Between January 2011 and July 2013, in 30 of 308 patients (10%) treated with radiotherapy after prostatectomy, pelvic lymphocele was detected on the simulation CT. The median lymphocele volume was 47 cm(3) (range, 6-467.3 cm(3)). Lymphocele was not included in planning target volume (PTV) in 8 cases (27%). Maximum dose to lymphocele was 57 Gy (range, 5.7-73.3 Gy). Radiotherapy was well tolerated. In all but 2 patients, lymphoceles remained asymptomatic. Lymphocele drainage-because of symptom occurrence-had to be performed in 2 patients during IMRT and in one patient, 7 weeks after IMRT. CBCT at the end of IMRT showed reduction in lymphocele volume and position compared with the initial data (median reduction of 37%), more pronounced in lymphoceles included in PTV. Radiotherapy after prostatectomy in the presence of pelvic asymptomatic lymphocele is feasible with acceptable acute and late toxicity. The volume of lymphoceles decreased during radiotherapy and this phenomenon might require intermediate radiotherapy plan evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Fiscal Year 2014 Source Reduction Assistance (SRA) Grant Summaries

EPA Pesticide Factsheets

The Office of Pollution Prevention and Toxics is responsible for overseeing several grant programs for tribes and states which promote pollution prevention through source reduction and resource conservation.

Fiscal Year 2015 Source Reduction Assistance (SRA) Grant Summaries

EPA Pesticide Factsheets

The Office of Pollution Prevention and Toxics is responsible for overseeing several grant programs for tribes and states which promote pollution prevention through source reduction and resource conservation.

About the Collision Repair Campaign

EPA Pesticide Factsheets

EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.

Safety, pharmacokinetics, and antitumor activity of AMG 386, a selective angiopoietin inhibitor, in adult patients with advanced solid tumors.

PubMed

Herbst, Roy S; Hong, David; Chap, Linnea; Kurzrock, Razelle; Jackson, Edward; Silverman, Jeffrey M; Rasmussen, Erik; Sun, Yu-Nien; Zhong, Don; Hwang, Yuying C; Evelhoch, Jeffrey L; Oliner, Jonathan D; Le, Ngocdiep; Rosen, Lee S

2009-07-20

PURPOSE AMG 386 is an investigational peptide-Fc fusion protein (ie, peptibody) that inhibits angiogenesis by preventing the interaction of angiopoietin-1 and angiopoietin-2 with their receptor, Tie2. This first-in-human study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of AMG 386 in adults with advanced solid tumors. PATIENTS AND METHODS Patients in sequential cohorts received weekly intravenous AMG 386 doses of 0.3, 1, 3, 10, or 30 mg/kg. Results Thirty-two patients were enrolled on the study and received AMG 386. One occurrence of dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest, which likely was caused by tumor burden that was possibly related to AMG 386. The most common toxicities were fatigue and peripheral edema. Proteinuria (n = 11) was observed without clinical sequelae. Only four patients (12%) experienced treatment-related toxicities greater than grade 1. A maximum-tolerated dose was not reached. PK was dose-linear and the mean terminal-phase elimination half-life values ranged from 3.1 to 6.3 days. Serum AMG 386 levels appeared to reach steady-state after four weekly doses, and there was minimal accumulation. No anti-AMG 386 neutralizing antibodies were detected. Reductions in volume transfer constant (K(trans); measured by dynamic contrast-enhanced magnetic resonance imaging) were observed in 10 patients (13 lesions) 48 hours to 8 weeks after treatment. One patient with refractory ovarian cancer achieved a confirmed partial response (ie, 32.5% reduction by Response Evaluation Criteria in Solid Tumors) and withdrew from the study with a partial response after 156 weeks of treatment; four patients experienced stable disease for at least 16 weeks. CONCLUSION Weekly AMG 386 appeared well tolerated, and its safety profile appeared distinct from that of vascular endothelial growth factor-axis inhibitors. AMG 386 also appeared to impact tumor vascularity and showed antitumor activity in this patient population.

Morpho-anatomical and growth alterations induced by arsenic in Cajanus cajan (L.) DC (Fabaceae).

PubMed

Pita-Barbosa, Alice; Gonçalves, Elton Carvalho; Azevedo, Aristéa Alves

2015-08-01

Arsenic (As) is a toxic element to most organisms. Studies investigating anatomic alterations due to As exposure in plants are scarce but of utmost importance to the establishment of environmental biomonitoring techniques. So, this study aimed to investigate the effects of As on the development and initial root growth in Cajanus cajan (Fabaceae), characterize and quantify the possible damages, evaluate genotoxic effects, and identify structural markers to be used in environmental bioindication. Plants were exposed hydroponically to 0.5, 1.0, 1.5, and 2.0 mg As L(-1), as sodium arsenate. Growth parameters were measured, and in the end of the exposure, root samples were analyzed for qualitative and quantitative anatomical alterations. Arsenic genotoxicity was evaluated through analysis of the mitotic index in the root apex. Compared to the control, As-treated seedlings showed an altered architecture, with significantly decreased root length (due to the lower mitotic index in the apical meristem and reduced elongation of parenchyma cells) with darkened color, and abnormal development of the root cap. A significant increase in vascular cylinder/root diameter ratio was also detected, due to the reduction of the cellular spaces in the cortex. The secondary xylem vessel elements were reduced in diameter and had sinuous walls. The severest damage was visible in the ramification zone, where uncommon division planes of phellogen and cambium cells and disintegration of the parenchyma cells adjacent to lateral roots were observed. The high sensibility of C. cajan to As was confirmed, since it caused severe damages in root growth and anatomy. The main structural markers for As toxicity were the altered root architecture, with the reduction of the elongation zone and increase of ramification zone length, and the root primordia retained within the cortex. Our results show a new approach about As toxicity and indicate that C. cajan is a promising species to be used for bioindication of environmental contamination by As.

Ethanol extract of Moringa oliefera prevents in vitro glucose induced cataract on isolated goat eye lens

PubMed Central

Kurmi, Raghvendra; Ganeshpurkar, Aditya; Bansal, Divya; Agnihotri, Abhishek; Dubey, Nazneen

2014-01-01

Aim of Study: The aim of current work was to evaluate in vitro anticataract potential of Moringa oliefera extract. Materials and Methods: Goat eye lenses were divided into 4 groups; Group served as control, Group II as toxic control, Group III and Group IV were incubated in extract (250 μg/ml and 500 μg/ml of extract of M. oliefera) Group II, III and IV were incubated in 55 mM glucose in artificial aqueous humor to induce lens opacification. Estimation of total, water soluble protein, catalase, glutathione and malondialdehyde along with photographic evaluation of lens was done. Results: Group II (toxic control) lenses showed high amount of MDA (Malondialdehyde), soluble, insoluble protein, decreased catalase and glutathione levels, while lenses treated with Moringa oliefera extract (Group III and Group IV) showed significant (* P < 0.05) reduction in MDA and increased level of catalase, glutathione, total and soluble protein. Conclusion: Results of present findings suggest protective effect of Moringa oliefera in prevention of in vitro glucose induced cataract. PMID:24008789

Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial.

PubMed

van den Berg, Henk; Paulussen, Michael; Le Teuff, Gwénaël; Judson, Ian; Gelderblom, Hans; Dirksen, Uta; Brennan, Bernadette; Whelan, Jeremy; Ladenstein, Ruth Lydia; Marec-Berard, Perrine; Kruseova, Jarmila; Hjorth, Lars; Kühne, Thomas; Brichard, Benedicte; Wheatley, Keith; Craft, Alan; Juergens, Heribert; Gaspar, Nathalie; Le Deley, Marie-Cécile

2015-11-01

Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. NCT00987636 and EudraCT 2008-003658-13. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of a Standardized Extract from Morus alba against α-Glucosidase Inhibitory Effect and Postprandial Antihyperglycemic in Patients with Impaired Glucose Tolerance: A Randomized Double-Blind Clinical Trial

PubMed Central

Hwang, Seung Hwan; Li, Hong Mei; Wang, Zhiqiang

2016-01-01

To evaluate the antihyperglycemic effect of a standardized extract of the leaves of Morus alba (SEMA), the present study was designed to investigate the α-glucosidase inhibitory effect and acute single oral toxicity as well as evaluate blood glucose reduction in animals and in patients with impaired glucose tolerance in a randomized double-blind clinical trial. SEMA was found to inhibit α-glucosidase at a fourfold higher level than the positive control (acarbose), in a concentration-dependent manner. Moreover, blood glucose concentration was suppressed by SEMA in vivo. Clinical signs and weight changes were observed when conducting an evaluation of the acute toxicity of SEMA through a single-time administration, with clinical observation conducted more than once each day. After administration of the SEMA, observation was for 14 days; all of the animals did not die and did not show any abnormal symptoms. In addition, the inhibitory effects of rice coated with SEMA were evaluated in a group of impaired glucose tolerance patients on postprandial glucose and a group of normal persons, and results showed that SEMA had a clear inhibitory effect on postprandial hyperglycemia in both groups. Overall, SEMA showed excellent potential in the present study as a material for improving postprandial hyperglycemia. PMID:27974904

Evaluation of Mobility, Bioavailability and Toxicity of Pb and Cd in Contaminated Soil Using TCLP, BCR and Earthworms

PubMed Central

Kede, Maria Luiza F. M.; Correia, Fabio V.; Conceição, Paulo F.; Salles Junior, Sidney F.; Marques, Marcia; Moreira, Josino C.; Pérez, Daniel V.

2014-01-01

The objective of the present study was to investigate the reduction of mobility, availability and toxicity found in soil contaminated with lead (Pb) and cadmium (Cd) from Santo Amaro Municipality, Bahia, Brazil using two combined methods, commonly tested separately according to the literature: metal mobilization with phosphates and phytoextraction. The strategy applied was the treatment with two sources of phosphates (separately and mixed) followed by phytoremediation with vetiver grass (Vetiveria zizanioides (L.)). The treatments applied (in triplicates) were: T1—potassium dihydrogen phosphate (KH2PO4); T2—reactive natural phosphate fertilizer (NRP) and; T3—a mixture 1:1 of KH2PO4 and NRP. After this step, untreated and treated soils were planted with vetiver grass. The extraction procedures and assays applied to contaminated soil before and after the treatments included metal mobility test (TCLP); sequential extraction with BCR method; toxicity assays with Eisenia andrei. The soil-to-plant transfer factors (TF) for Pb and Cd were estimated in all cases. All treatments with phosphates followed by phytoremediation reduced the mobility and availability of Pb and Cd, being KH2PO4 (T1) plus phytoremediation the most effective one. Soil toxicity however, remained high after all treatments. PMID:25386955

Toxic effect of NiCl2 on development of the bursa of Fabricius in broiler chickens

PubMed Central

Yin, Shuang; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan; Guo, Hongrui

2016-01-01

This study was conducted with objective of evaluating the toxic effects of nickel chloride (NiCl2) on development of bursa of Fabricius in broilers fed on diets supplemented with 0, 300, 600 and 900 mg/kg of NiCl2 for 42 days by using the methods of experimental pathology, flow cytometry (FCM), and quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that dietary NiCl2 in 300 mg/kg and over induced toxic suppression in the bursal development, which was characterized by decreasing lymphocytes histopathologically and relative weight, increasing G0/G1 phase (a prolonged nondividing state), reducing S phase (DNA replication) and proliferating index, and increasing percentages of apoptotic cells. Concurrently, the mRNA expression levels of bax, cytochrome c (cyt c), apoptotic peptidase activating factor 1 (Apaf-1), caspase-3, caspase-6, caspase-7 and caspase-9 were increased and the bcl-2 mRNA expression levels were decreased. The toxic suppression of bursal development finally impaired humoral immunity duo to the reduction of B lymphocyte population and B lymphocyte activity in the broiler chicken. This study provides new evidences for further studying the effect mechanism of Ni and Ni compoundson B-cell or bursa of Fabricius. PMID:26683707

Acute and sub-chronic toxicological evaluation of hydro-methanolic extract of Coriandrum sativum L. seeds

PubMed Central

Patel, Dipak; Desai, Swati; Devkar, Ranjitsinh; Ramachandran, A.V.

2012-01-01

Coriandrum sativum L. (CS) seeds are known to possess therapeutic potentials against a variety of physiological disorders. This study assesses acute and sub-chronic toxicity profile of hydro-methanolic extract of CS seeds using OECD guidelines. In acute toxicity study, mice were once orally administered 1000, 3000 and 5000 mg/kg body weight of CS extract. There were no any behavioral alterations or mortality recorded in CS treated groups. The LD50 value was more than 5000 mg/kg body weight. In the sub-chronic oral toxicity study, the animals were orally administered with CS extract (1000, 2000 and 3000mg/kg body weight) daily for 28 days whereas; vehicle control group received 0.5 % carboxy methyl cellulose. There was significant reduction in food intake, body weight gain and plasma lipid profiles of CS2 and CS3 (2000 and 3000 mg/kg body weight respectively) groups as compared to the control group. However, there were no alterations in haematological profile, relative organ weights, histology and plasma markers of damage of vital organs (heart, liver and kidney). The overall finding of this study indicates that CS extract is non-toxic up to 3000 mg/kg body weight and can be considered as safe for consumption. PMID:27847445

Coupling of OECD standardized test and immunomarkers to select the most environmentally benign ionic liquids option--towards an innovative "safety by design" approach.

PubMed

Bado-Nilles, Anne; Diallo, Alpha-Oumar; Marlair, Guy; Pandard, Pascal; Chabot, Laure; Geffard, Alain; Len, Christophe; Porcher, Jean-Marc; Sanchez, Wilfried

2015-01-01

This paper proposed a potential industrial accompaniment to reduce ionic liquid harmfulness by a novel combination of OECD Daphnia magna standardized test and fish immunomarkers. The combination of these two tests allowed multicriteria examination of ILs impacts in different organisms and trophic levels. The work provided new data for legislation and opened a door towards an integrative environmental evaluation due to direct implications of immune system in fish and ecosystem health. Whatever the species, each IL tested induced deleterious effects suggesting that toxic impact was especially due to IL lipophilicity properties. Nevertheless, cation moieties of ILs seemed to draw overall toxicity of ILs to significant extent as supported by lower cell mortality shown with imidazolium-based ILs compared to phosphonium-based ILs. However, the anions moieties have some additional effect, as revealed by quite dissimilar toxicity within same IL family. Concerning the more integrative biomarkers, the cationic-based ILs tested possessed also dissimilar effect on immune system of fish, especially on leucocyte distribution, lysosomal membrane integrity and phagocytosis activity. These results confirm that ILs toxicity could be influenced by design and that chemical engineering processes can integrate ecological footprint reduction strategies for successful IL utilization in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of increasing nitrogen and phosphorus concentrations on phytoplankton community growth and toxicity during Planktothrix blooms in Sandusky Bay, Lake Erie.

PubMed

Davis, Timothy W; Bullerjahn, George S; Tuttle, Taylor; McKay, Robert Michael; Watson, Susan B

2015-06-16

Sandusky Bay experiences annual toxic cyanobacterial blooms dominated by Planktothrix agardhii/suspensa. To further understand the environmental drivers of these events, we evaluated changes in the growth response and toxicity of the Planktothrix-dominated blooms to nutrient amendments with orthophosphate (PO4) and inorganic and organic forms of dissolved nitrogen (N; ammonium (NH4), nitrate (NO3) and urea) over the bloom season (June - October). We complemented these with a metagenomic analysis of the planktonic microbial community. Our results showed that bloom growth and microcystin (MC) concentrations responded more frequently to additions of dissolved N than PO4, and that the dual addition of NH4 + PO4 and Urea + PO4 yielded the highest MC concentrations in 54% of experiments. Metagenomic analysis confirmed that P. agardhii/suspensa was the primary MC producer. The phylogenetic distribution of nifH revealed that both heterocystous cyanobacteria and heterotrophic proteobacteria had the genetic potential for N2 fixation in Sandusky Bay. These results suggest that as best management practices are developed for P reductions in Sandusky Bay, managers must be aware of the negative implications of not managing N loading into this system as N may significantly impact cyanobacterial bloom size and toxicity.

Alternatives to animal testing: research, trends, validation, regulatory acceptance.

PubMed

Huggins, Jane

2003-01-01

Current trends and issues in the development of alternatives to the use of animals in biomedical experimentation are discussed in this position paper. Eight topics are considered and include refinement of acute toxicity assays; eye corrosion/irritation alternatives; skin corrosion/irritation alternatives; contact sensitization alternatives; developmental/reproductive testing alternatives; genetic engineering (transgenic) assays; toxicogenomics; and validation of alternative methods. The discussion of refinement of acute toxicity assays is focused primarily on developments with regard to reduction of the number of animals used in the LD(50) assay. However, the substitution of humane endpoints such as clinical signs of toxicity for lethality in these assays is also evaluated. Alternative assays for eye corrosion/irritation as well as those for skin corrosion/irritation are described with particular attention paid to the outcomes, both successful and unsuccessful, of several validation efforts. Alternative assays for contact sensitization and developmental/reproductive toxicity are presented as examples of methods designed for the examination of interactions between toxins and somewhat more complex physiological systems. Moreover, genetic engineering and toxicogenomics are discussed with an eye toward the future of biological experimentation in general. The implications of gene manipulation for research animals, specifically, are also examined. Finally, validation methods are investigated as to their effectiveness, or lack thereof, and suggestions for their standardization and improvement, as well as implementation are reviewed.

Detection of Androgenic-Mutagenic Compounds and Potential Autochthonous Bacterial Communities during In Situ Bioremediation of Post-methanated Distillery Sludge

PubMed Central

Chandra, Ram; Kumar, Vineet

2017-01-01

Sugarcane-molasses-based post-methanated distillery waste is well known for its toxicity, causing adverse effects on aquatic flora and fauna. Here, it has been demonstrated that there is an abundant mixture of androgenic and mutagenic compounds both in distillery sludge and leachate. Gas chromatography-mass spectrometry (GC-MS) analysis showed dodecanoic acid, octadecanoic acid, n-pentadecanoic acid, hexadecanoic acid, β-sitosterol, stigmasterol, β-sitosterol trimethyl ether, heptacosane, dotriacontane, lanosta-8, 24-dien-3-one, 1-methylene-3-methyl butanol, 1-phenyl-1-propanol, 5-methyl-2-(1-methylethyl) cyclohexanol, and 2-ethylthio-10-hydroxy-9-methoxy-1,4 anthraquinone as major organic pollutants along with heavy metals (all mg kg-1): Fe (2403), Zn (210.15), Mn (126.30, Cu (73.62), Cr (21.825), Pb (16.33) and Ni (13.425). In a simultaneous analysis of bacterial communities using the restriction fragment length polymorphism (RFLP) method the dominance of Bacillus sp. followed by Enterococcus sp. as autochthonous bacterial communities growing in this extremely toxic environment was shown, indicating a primary community for bioremediation. A toxicity evaluation showed a reduction of toxicity in degraded samples of sludge and leachate, confirming the role of autochthonous bacterial communities in the bioremediation of distillery waste in situ. PMID:28567033

In vitro methods of assessing ocular biocompatibility using THP-1-derived macrophages.

PubMed

McCanna, David Joseph; Barthod-Malat, Aurore V; Gorbet, Maud B

2015-01-01

Macrophages play an important role in the elimination of infections, the removal of debris and in tissue repair after infection and trauma. In vitro models that assess ocular biomaterials for toxicity typically focus on the effects of these materials on epithelial or fibroblast cells. This investigation evaluated known ocular toxins deposited on model materials for their effects on the viability and activation of macrophages. THP-1-derived macrophages were cultured onto silicone films (used as a base biomaterial) deposited with chemical toxins (benzalkonium chloride (BAK), zinc diethyldithiocarbamate (ZDEC) and lipopolysaccharide (LPS)). Utilizing three fluorescent dyes calcein, ethidium homodimer-1 (EthD-1) and annexin V, the viability of macrophages attached to the biomaterial was determined using confocal microscopy. Propidium iodide (PI) staining and alamarBlue® (resazurin) reduction were used to assess cell death and metabolic activity. CD14, CD16, CD33, CD45, and CD54 expression of adherent macrophages, were also evaluated to detect LPS activation of macrophages using flow cytometry. The sensitivity of this test battery was demonstrated as significant toxicity from treated surfaces with ZDEC (0.001-0.01%), and BAK (0.001%-0.1%) was detected. Also, macrophage activation could be detected by measuring CD54 expression after exposure to adsorbed LPS. These in vitro methods will be helpful in determining the toxicity potential of new ocular biomaterials.

Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig

PubMed Central

Kasali, Félicien Mushagalusa; Kadima, Justin Ntokamunda; Mpiana, Pius Tshimankinda; Ngbolua, Koto-te-Nyiwa; Tshibangu, Damien Sha-Tshibey

2013-01-01

Objective To verify the antidiabetic activity of leaf extracts from Physalis peruviana L. popularly used in the Eastern part of the Democratic Republic of the Congo and to point out the possible toxicity. Method Aqueous decoctions prepared from dried leaves powder were administrated to guinea pigs at the dose range of 100 mg/kg to 3.2 g/kg of body weight. The hypoglycemic activity was evaluated by glucose tolerance test, loading animals with glucose 4 g/kg and measuring blood glucose concentrations at various times. The effect was compared to the control and glibenclamide as antidiabetic reference drug. Acute toxicity was evaluated by recording mortality rate, changes on blood biomarkers and damage caused to vital organs. Results At a dose of 100 mg/kg, the aqueous extract induced a significant reduction of peak concentration at 30 min after glucose loading as compared with control or reference (P<0.05). At doses greater than 400 mg, some alterations on blood, kidney and liver markers were observed. Upper 800 mg/kg, mortality was observed with LD50 estimated at about 1 280 mg/kg. At the autopsy, vital organs were in haemorrhage and swelling state. Conclusion The crude aqueous extracts from the leaves of Physalis peruviana L. present hypoglycemic activity in animal model, but at high doses the plant may cause severe intoxication.

Evaluation of remediation techniques in soils affected by residual contamination with heavy metals and arsenic.

PubMed

García-Carmona, M; Romero-Freire, A; Sierra Aragón, M; Martínez Garzón, F J; Martín Peinado, F J

2017-04-15

Residual soil pollution from the Aznalcóllar mine spill is still a problem in some parts of the affected area, today converted in the Guadiamar Green Corridor. Dispersed spots of polluted soils, identified by the absence of vegetation, are characterized by soil acid pH and high concentrations of As, Pb, Cu and Zn. Ex situ remediation techniques were performed with unrecovered soil samples. Landfarming, Composting and Biopiles techniques were tested in order to immobilize pollutants, to improve soil properties and to promote vegetation recovery. The effectiveness of these techniques was assessed by toxicity bioassays: Lactuca sativa L. root elongation test, Vibrio fischeri bioluminescence reduction test, soil induced respiration test, and Eisenia andrei survival and metal bioaccumulation tests. Landfarming and Composting were not effective techniques, mainly due to the poor improvement of soil properties which maintained high soluble concentrations of Zn and Cu after treatments. Biopile technique, using adjacent recovered soils in the area, was the most effective action in the reduction of soil toxicity; the improvement of soil properties and the reduction in pollutants solubility were key to improve the response of the tested organisms. Therefore, the mixture of recovered soils with polluted soils in the areas affected by residual contamination is considered a more suitable technique to reduce the residual pollution and to promote the complete soil recovery in the Guadiamar Green Corridor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Treatment with tandem [90Y]DOTA-TATE and [177Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy.

PubMed

Seregni, E; Maccauro, M; Chiesa, C; Mariani, L; Pascali, C; Mazzaferro, V; De Braud, F; Buzzoni, R; Milione, M; Lorenzoni, A; Bogni, A; Coliva, A; Lo Vullo, S; Bombardieri, E

2014-02-01

Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ((90)Y) and a medium-energy beta/gamma emitter ([(177)Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [[(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [[(177)Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [(90)Y]DOTA-TATE and [[(177)Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment. The results of our study indicates that combined [(90)Y]DOTA-TATE and [(177)Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach.

Microbial reductive dehalogenation.

PubMed Central

Mohn, W W; Tiedje, J M

1992-01-01

A wide variety of compounds can be biodegraded via reductive removal of halogen substituents. This process can degrade toxic pollutants, some of which are not known to be biodegraded by any other means. Reductive dehalogenation of aromatic compounds has been found primarily in undefined, syntrophic anaerobic communities. We discuss ecological and physiological principles which appear to be important in these communities and evaluate how widely applicable these principles are. Anaerobic communities that catalyze reductive dehalogenation appear to differ in many respects. A large number of pure cultures which catalyze reductive dehalogenation of aliphatic compounds are known, in contrast to only a few organisms which catalyze reductive dehalogenation of aromatic compounds. Desulfomonile tiedjei DCB-1 is an anaerobe which dehalogenates aromatic compounds and is physiologically and morphologically unusual in a number of respects, including the ability to exploit reductive dehalogenation for energy metabolism. When possible, we use D. tiedjei as a model to understand dehalogenating organisms in the above-mentioned undefined systems. Aerobes use reductive dehalogenation for substrates which are resistant to known mechanisms of oxidative attack. Reductive dehalogenation, especially of aliphatic compounds, has recently been found in cell-free systems. These systems give us an insight into how and why microorganisms catalyze this activity. In some cases transition metal complexes serve as catalysts, whereas in other cases, particularly with aromatic substrates, the catalysts appear to be enzymes. Images PMID:1406492

Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial.

PubMed

Dogliotti, Luigi; Cartenì, Giacomo; Siena, Salvatore; Bertetto, Oscar; Martoni, Andrea; Bono, Aldo; Amadori, Dino; Onat, Haluk; Marini, Luca

2007-07-01

This phase 2 randomized study compared the toxicity and assessed the efficacy of gemcitabine-cisplatin (GP) and gemcitabine-carboplatin (GC) in patients with advanced transitional cell carcinoma of the urothelium (TCC), with the main objective to demonstrate a reduction in toxicity of at least 25% in the GC arm. A total of 110 chemonaive patients (55 per arm) with locally advanced or metastatic TCC received gemcitabine 1250 mg/m(2) on days 1 and 8 plus cisplatin 70 mg/m(2) on day 2 (GP) every 3 wk or gemcitabine 1250 mg/m(2) on days 1 and 8 plus carboplatin AUC 5 on day 2 (GC) every 3 wk for a maximum of six cycles. No differences between arms were noted in the overall toxicity profiles and any parameter of toxicity. The most frequent grade 3-4 hematologic toxicity was neutropenia in 34.6% of patients for GP and 45.4% for GC. The most frequent grade 3-4 nonhematologic toxicity was nausea and vomiting (GP: 9.1%; GC: 3.6%). Grade 1-2 nephrotoxicity occurred in 14 GP-treated patients (26.0%) and 9 GC-treated patients (16.3%). Per an intent-to-treat analysis, overall response, evaluated on 80 patients, was 49.1% for GP (CR: 14.5%; PR: 34.5%) and 40.0% for GC (CR: 1.8%; PR: 38.2%). Median time to progression was 8.3 mo for GP and 7.7 mo for GC. Median survival was 12.8 mo and 9.8 mo for GP and GC, respectively. GC has a comparably acceptable toxicity profile compared with that of GP and seems active in patients with TCC.

Cytogenetic evaluation of gold nanorods using Allium cepa test.

PubMed

Rajeshwari, A; Roy, Barsha; Chandrasekaran, Natarajan; Mukherjee, Amitava

2016-12-01

The current study reveals the impact of gold nanorods (NRs) capped with CTAB (cetyltrimethylammonium bromide) or PEG (polyethylene glycol) on Allium cepa. The morphology and surface charge of CTAB- and PEG-capped gold NRs were characterized by electron microscopic and zeta potential analyses. The chromosomal aberrations like clumped chromosome, chromosomal break, chromosomal bridge, diagonal anaphase, disturbed metaphase, laggard chromosome, and sticky chromosome were observed in the root tip cells exposed to different concentrations (0.1, 1, and 10 μg/mL) of CTAB- and PEG-capped gold NRs. We found that both CTAB- and PEG-capped gold NRs were able to induce toxicity in the plant system after 4-h interaction. At a maximum concentration of 10 μg/mL, the mitotic index reduction induced by CTAB-capped gold NRs was 40-fold higher than that induced by PEG-capped gold NRs. The toxicity of gold NRs was further confirmed by lipid peroxidation and oxidative stress analyses. The unbound CTAB also contributed to the toxicity in root tip cells, while PEG alone shows less toxicity to the cells. The vehicle control CTAB contributed to the toxic effects in root tip cells, while PEG alone did not show any toxicity to the cells. The results revealed that even though both the particles have adverse effects on A. cepa, there was a significant difference in the mitotic index and oxidative stress generation in root cells exposed to CTAB-capped gold NRs. Thus, this study concludes that the surface polymerization of gold NRs by PEG can reduce the toxicity of CTAB-capped gold NRs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Investigation of olive mill wastewater (OMW) ozonation efficiency with the use of a battery of selected ecotoxicity and human toxicity assays.

PubMed

Siorou, Sofia; Vgenis, Theodoros T; Dareioti, Margarita A; Vidali, Maria-Sophia; Efthimiou, Ioanna; Kornaros, Michael; Vlastos, Dimitris; Dailianis, Stefanos

2015-07-01

The effects of olive mill wastewater (OMW) on a battery of biological assays, before and during the ozonation process, were investigated in order to assess ozone's efficiency in removing phenolic compounds from OMW and decreasing the concomitant OMW toxicity. Specifically, ozonated-OMW held for 0, 60, 120, 300, 420, 540min in a glass bubble reactor, showed a drastic reduction of OMW total phenols (almost 50%) after 300min of ozonation with a concomitant decrease of OMW toxicity. In particular, the acute toxicity test primarily performed in the fairy shrimp Thamnocephalus platyurus (Thamnotoxkit F™ screening toxicity test) showed a significant attenuation of OMW-induced toxic effects, after ozonation for a period of 120 and in a lesser extent 300min, while further treatment resulted in a significant enhancement of ozonated-OMW toxic effects. Furthermore, ozonated-OMW-treated mussel hemocytes showed a significant attenuation of the ability of OMW to cause cytotoxic (obtained by the use of NRRT assay) effects already after an ozonation period of 120 and to a lesser extent 300min. In accordance with the latter, OMW-mediated oxidative (enhanced levels of superoxide anions and lipid peroxidation by-products) and genotoxic (induction of DNA damage) effects were diminished after OMW ozonation for the aforementioned periods of time. The latter was also revealed by the use of cytokinesis block micronucleus (CBMN) assay in human lymphocytes exposed to different concentrations of both raw- and ozonated-OMW for 60, 120 and 300min. Those findings revealed for a first time the existence of a critical time point during the OMW ozonation process that could be fundamentally used for evaluating OMW ozonation as a pretreatment method of OMW. Copyright © 2015 Elsevier B.V. All rights reserved.

[Harm reduction strategy in tobacco control].

PubMed

Gorini, Giuseppe

2011-01-01

Potentially reduced exposure products (PREPs), already sold in USA and in some European Countries, are low-nitrosamine cigarettes, low-nitrosamine smokeless tobacco (e.g., the Swedish Snus), cigarette-like products, and medicinal nicotine products. Even e-cigarette delivers nicotine. With the exception of snus and medicinal nicotine, studies on the health effects of PREPs have not been carried out, although some PREPs are already sold and promoted as products that effectively reduce health risks. Thus, a second disaster similar to that occurred for light cigarettes could happen in the next years. Only medicinal nicotine and snus could be valid candidates to become PREPs, even if they pose some significant health risks. The World Health Organization, following a precautionary approach, has recently published a list of 9 carcinogens or toxicants recommended for mandated lowering (the tobacco-specific nitrosamines NNN and NNK, acetaldehyde, acrolein, benzene, benzo[a]pyrene, 1-3 butadiene, carbon monoxide, formaldehyde), and 9 carcinogens or toxicants for monitoring in usual cigarettes (not PREPs), underlining that tobacco companies cannot use this reduction strategy as a promotional message, as it occurred for light cigarettes in the 70s and 80s. The present status quo, in which cigarettes are freely available, medicinal nicotine, being a drug, is available under a regulated market, and Snus is prohibited, actually denies smokers the right to choose safer nicotine products. The solution suggested by the UK Royal College of Physicians is to balance the nicotine market, framing tobacco products and medicinal nicotine in the same regulation system; establishing a nicotine and tobacco regulatory authority;making medicinal nicotine more available; evaluating the feasibility of the introduction in the English market of Swedish Snus. California Government remarks that the nicotine maintenance is not a valid strategy, because it could induce smokers not to try to quit.Thus, California Department of Health Services prohibits promotion of snus and medicinal nicotine as a harm reduction strategy. However, the US Federal Family Smoking Prevention and Tobacco Control Act, signed by President Obama in 2009, places tobacco products under FDA jurisdiction: FDA must define criteria for lowering carcinogens and toxicants in tobacco products, making more available medicinal nicotine, evaluating PREPs, creating a federal Tobacco Control Agency.Which approaches is Italy going to follow?

Plantago lanceolata and Plantago rugelii Extracts are Toxic to Meloidogyne incognita but not to Certain Microbes

PubMed Central

Meyer, Susan L. F.; Zasada, Inga A.; Roberts, Daniel P.; Vinyard, Bryan T.; Lakshman, Dilip K.; Lee, Jae-Kook; Chitwood, David J.; Carta, Lynn K.

2006-01-01

Extracts from the plants Plantago lanceolata and P. rugelii were evaluated for toxicity to the root-knot nematode Meloidogyne incognita, the beneficial microbes Enterobacter cloacae, Pseudomonas fluorescens and Trichoderma virens, and the plant-pathogenic fungi Fusarium oxysporum f. sp. gladioli, Phytophthora capsici, Pythium ultimum, and Rhizoctonia solani. Wild plants were collected, roots were excised from shoots, and the plant parts were dried and ground to a powder. One set of extracts (10% w/v) was prepared in water and another in methanol. Treatments included extract concentrations of 25%, 50%, 75% and 100%, and water controls. Meloidogyne incognita egg hatch was recorded after 7-day exposure to the treatments, and second-stage juvenile (J2) activity after 48 hours. All extracts were toxic to eggs and J2, with P. lanceolata shoot extract tending to have the most activity against M. incognita. Numbers of active J2 remained the same or decreased in a 24-hour water rinse following the 48-hour extract treatment, indicating that the extracts were lethal. When data from water- and methanol-extracted roots and shoots of both plant species were combined for analysis, J2 tended to be more sensitive than eggs to the toxic compounds at lower concentrations, while the higher concentrations (75% and 100%) were equally toxic to both life stages. The effective concentrations causing 50% reduction (EC50) in egg hatch and in J2 viability were 44.4% and 43.7%, respectively. No extract was toxic to any of the bacteria or fungi in our assays. PMID:19259537

Negundoside, an iridiod glycoside from leaves of Vitex negundo, protects human liver cells against calcium-mediated toxicity induced by carbon tetrachloride

PubMed Central

Tasduq, Sheikh A; Kaiser, Peerzada J; Gupta, Bishan D; Gupta, Vijay K; Johri, Rakesh K

2008-01-01

AIM: To evaluate the protective effect of 2'-p-hydroxybenzoylmussaenosidic acid [negundoside (NG), against carbon tetrachloride (CCl4)-induced toxicity in HuH-7 cells. METHODS: CCl4 is a well characterized hepatotoxin, and inducer of cytochrome P450 2E1 (CYP2E1)-mediated oxidative stress. In addition, lipid peroxidation and accumulation of intracellular calcium are important steps in the pathway involved in CCl4 toxicity. Liver cells (HuH-7) were treated with CCl4, and the mechanism of the cytoprotective effect of NG was assessed. Silymarin, a known hepatoprotective drug, was used as control. RESULTS: NG protected HuH-7 cells against CCl4 toxicity and loss of viability without modulating CYP2E1 activity. Prevention of CCl4 toxicity was associated with a reduction in oxidative damage as reflected by decreased generation of reactive oxygen species (ROS), a decrease in lipid peroxidation and accumulation of intracellular Ca2+ levels and maintenance of intracellular glutathione homeostasis. Decreased mitochondrial membrane potential (MMP), induction of caspases mediated DNA fragmentation and cell cycle arrest, as a result of CCl4 treatment, were also blocked by NG. The protection afforded by NG seemed to be mediated by activation of cyclic adenosine monophosphate (cAMP) synthesis and inhibition of phospholipases (cPLA2). CONCLUSION: NG exerts a protective effect on CYP2E1-dependent CCl4 toxicity via inhibition of lipid peroxidation, followed by an improved intracellular calcium homeostasis and inhibition of Ca2+-dependent proteases. PMID:18595136

Safety Assessment of Ocimum Basilicum Hydroalcoholic Extract in Wistar Rats: Acute and Subchronic Toxicity Studies

PubMed Central

Rasekh, Hamid Reza; Hosseinzadeh, Leila; Mehri, Soghra; Kamli-Nejad, Mohammad; Aslani, Majid; Tanbakoosazan, Farahnaz

2012-01-01

Objective(s) Ocimum basilicum L. is widely used in folk medicine of many countries including . Both O. basilicum and its oil extract have received considerable attention for their potential medicinal properties, but there are a few reports about possible toxicity of this plant. Therefore, in the present study, acute and subchronic toxicity of O. basilicum hydroalcohlic extract have been evaluated in Wistar rats. Materials and Methods For the acute toxicity assessment, five groups of 10 animals (5 male, 5 female) received four different single dose of extract orally, the animals were, then, kept under observation for 14 days. For subchronic toxicity, the animals were divided into four groups (5 male, 5 female) and were gavaged daily by 50, 200 and 500 mg/kg of extract. Mortality, clinical signs, body weight changes, food and water consumption, and hematological and biochemical parameters were monitored during the study period. On the 45th day, animals were sacrificed and gross findings, weight of liver and left kidney and liver histological markers were assessed. Results The results of acute study indicated that LD50 of O. basilicum is higher than 5 mg/kg. In subchronic study, no adverse effects were observed on serum parameters in male and female rats. The hematological results showed a reduction in the hematocrit, platelets and RBC in both sexes. No abnormalities were observed in other parameters. Conclusion Based on the results of this study, present data suggest that hematologic system could serve as a target organ in oral toxicity of this plant. PMID:23493182

SUSPECTED HYPERVITAMINOSIS D IN RED-RUMPED AGOUTI ( DASYPROCTA LEPORINA) RECEIVING A COMMERCIAL RODENT DIET.

PubMed

Anderson, Kadie M; Lewandowski, Albert; Dennis, Patricia M

2018-03-01

An 8 yr, intact male red-rumped agouti ( Dasyprocta leporina) was evaluated for weight loss. Examination revealed poor body condition, hypercalcemia, elevated serum 25-hydroxyvitamin D, metastatic calcification of soft tissues, and hyperechoic kidneys. The diet, formulated for laboratory rodents, contained elevated levels of vitamin D 3 . Histopathology from a female conspecific that died 5 mo prior identified dystrophic mineralization and nephrosclerosis, suggestive of a vitamin D 3 toxicity. The male agouti responded well to a dietary reduction in vitamin D 3 and calcium. Six months into therapy, progressive renal failure was identified and was further managed with enalapril, phosphorus binders, and dietary manipulation. Suspected vitamin D 3 toxicity has been reported in pacas ( Cuniculus paca) and agouti and has been linked to exposure to New World primate diets. In this brief communication, an agouti developed suspected hypervitaminosis D after receiving a commercial rodent diet commonly fed to this species in captivity.

A comparison of Eichhornia crassipes (Pontederiaceae) and Sphagnum quinquefarium (Sphagnaceae) in treatment of acid mine water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Falbo, M.B.; Weaks, T.E.

Tests were conducted under greenhouse conditions to evaluate the ability of Eichhornia crassipes (Pontederiaceae) and Sphagnum quinquefarium (Sphagnaceae) to ameliorate acid mine water discharged from coal operations. In addition, the survivorship and growth rate of E. crassipes (water-hyacinth), cultured in toxic acid mine water, were determined. The results of both short- and long-term studies indicated that E. crassipes readily reduced levels of heavy metals in acid mine water while the plants exhibited few signs of toxicity. Patterns of reduction of pollutants, for both E. crassipes and S. quinquefarium indicated that treatment efficiency could be improved by the periodic harvesting ofmore » plants. It is suggested that the ease with which water-hyacinths can be introduced into wetlands and harvested cannot be economically duplicated with other plants currently in use in treating acid mine water.« less

N,N'-disubstituted cinnamamide derivatives potentiate ciprofloxacin activity against overexpressing NorA efflux pump Staphylococcus aureus 1199B strains.

PubMed

Radix, Sylvie; Jordheim, Anne Doléans; Rocheblave, Luc; N'Digo, Serge; Prignon, Anne-Laure; Commun, Carine; Michalet, Serge; Dijoux-Franca, Marie-Geneviève; Mularoni, Angélique; Walchshofer, Nadia

2018-04-25

A multi-step procedure has been described which afforded satisfactory yields of N,N'-disubstituted cinnamamides derived from N-Boc-protected amino acids (Boc-Gly, Boc-Val, Boc-Phe). The key step of this synthesis was a regioselective RedAl reduction of an amide function in presence of a carbamate group. Next, these cinnamamides were evaluated in co-admnistration with ciprofloxacin as efflux pump inhibitors against two S. aureus strains, NorA overexpressing SA1199B and wild type SA1199. In parallel, their intrinsic toxicity was appreciated on human lung fibroblast MRC5 cells. Therefore, the cinnamamide combining both carbamate and indol-3-yl groups, was found to be the most active and one of the less toxic EPI and constituted a promising hit. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Antibacterial and Antifungal Activity of ZnO Containing Glasses.

PubMed

Esteban-Tejeda, Leticia; Prado, Catuxa; Cabal, Belén; Sanz, Jesús; Torrecillas, Ramón; Moya, José Serafín

2015-01-01

A new family of non-toxic biocides based on low melting point (1250°C) transparent glasses with high content of ZnO (15-40wt%) belonging to the miscibility region of the B2O3-SiO2-Na2O-ZnO system has been developed. These glasses have shown an excellent biocide activity (logarithmic reduction >3) against Gram- (E. coli), Gram+ (S. aureus) and yeast (C. krusei); they are chemically stable in different media (distilled water, sea-like water, LB and DMEN media) as well as biocompatible. The cytotoxicity was evaluated by the Neutral Red Uptake using NIH-3T3 (mouse embryonic fibroblast cells) and the cell viability was >80%. These new glasses can be considered in several and important applications in the field of inorganic non-toxic biocide agents such as medical implants, surgical equipment, protective apparels in hospitals, water purifications systems, food packaging, food storages or textiles.

Antibacterial and Antifungal Activity of ZnO Containing Glasses

PubMed Central

Esteban-Tejeda, Leticia; Prado, Catuxa; Cabal, Belén; Sanz, Jesús; Torrecillas, Ramón; Moya, José Serafín

2015-01-01

A new family of non-toxic biocides based on low melting point (1250°C) transparent glasses with high content of ZnO (15–40wt%) belonging to the miscibility region of the B2O3-SiO2-Na2O-ZnO system has been developed. These glasses have shown an excellent biocide activity (logarithmic reduction >3) against Gram- (E. coli), Gram+ (S. aureus) and yeast (C. krusei); they are chemically stable in different media (distilled water, sea-like water, LB and DMEN media) as well as biocompatible. The cytotoxicity was evaluated by the Neutral Red Uptake using NIH-3T3 (mouse embryonic fibroblast cells) and the cell viability was >80%. These new glasses can be considered in several and important applications in the field of inorganic non-toxic biocide agents such as medical implants, surgical equipment, protective apparels in hospitals, water purifications systems, food packaging, food storages or textiles. PMID:26230940

Analgesic, anti-inflammatory, antipyretic and haematological effects of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives.

PubMed

Hernández-Pérez, M; Rabanal, R M; de la Torre, M C; Rodríguez, B

1995-12-01

Aethiopinone (1), an o-naphthoquinone diterpene from Salvia aethiopis L. roots and two hemisynthetic derivatives 2 and 3 have been evaluated for toxicity, anti-inflammatory, analgesic, antipyretic, and haemostatic activities. The compounds tested showed low toxicity and a pharmacological profile similar to other NSAI substances on reducing the edema induced by carrageenan and contractions induced by phenyl-p-quinone; the most active compounds were 1 and 2. In the same way and as expected with these types of substances, the bleeding time increased. In the TPA-induced ear inflammation model, the three compounds showed a moderate reduction of edema, and 1 produced a significant increase in the reaction time against thermal painful stimuli in the tail immersion test. The results demonstrated strong anti-inflammatory, peripheral and central analgesic properties for 1, as well as antiedematose topical action and peripheral analgesic properties for 2 and 3.

Susceptibility to 6-MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia.

PubMed

Tanaka, Yoichi; Kato, Motohiro; Hasegawa, Daisuke; Urayama, Kevin Y; Nakadate, Hisaya; Kondoh, Kensuke; Nakamura, Kozue; Koh, Katsuyoshi; Komiyama, Takako; Manabe, Atsushi

2015-10-01

Genotyping of TPMT prior to 6-mercaptopurine (6-MP) administration in acute lymphoblastic leukaemia (ALL) patients has been integrated into clinical practice in some populations of European ancestry. However, the comparable rates of 6-MP myelotoxicity, but rarity of TPMT variants, in Asians suggest that major determinants have yet to be discovered in this population. We genotyped 92 Japanese paediatric ALL patients for NUDT15 rs116855232, a 6-MP toxicity-related locus discovered in Asians. Logistic regression and survival analysis were used to evaluate its association with leucopenia, hepatotoxicity, 6-MP dose reduction, therapy interruption and event-free survival. The allele frequency of rs116855232 was 0·16, and leucopenia was more common in carriers of the T allele (odds ratio, 7·20; 95% confidence interval, 2·49-20·80; P = 2·7 × 10(-4) ). As leucopenia results in 6-MP dose reduction, we observed average doses during maintenance therapy of 40·7, 29·3 and 8·8 mg/m(2) for patients with CC, CT and TT genotypes, respectively (P < 0·001). Hepatotoxicity was observed only in CC genotype patients. Event-free survival did not significantly differ by NUDT15 genotype. rs116855232 is an important determinant of 6-MP myelotoxicity in Japanese children with ALL and may represent the most robust toxicity-related locus in Asians to date. Considerations for clinical application may be warranted. © 2015 John Wiley & Sons Ltd.

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

NASA Astrophysics Data System (ADS)

Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

2016-09-01

Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity.

PubMed

Szczepanowicz, Krzysztof; Jantas, Danuta; Piotrowski, Marek; Staroń, Jakub; Leśkiewicz, Monika; Regulska, Magdalena; Lasoń, Władysław; Warszyński, Piotr

2016-09-02

Poor water solubility and low bioavailability of lipophilic drugs can be potentially improved with the use of delivery systems. In this study, encapsulation of nanoemulsion droplets was utilized to prepare curcumin nanocarriers. Nanosize droplets containing the drug were encapsulated in polyelectrolyte shells formed by the layer-by-layer (LbL) adsorption of biocompatible polyelectrolytes: poly-L-lysine (PLL) and poly-L-glutamic acid (PGA). The size of synthesized nanocapsules was around 100 nm. Their biocompatibility and neuroprotective effects were evaluated on the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). Statistically significant toxic effect was clearly observed for PLL coated nanocapsules (reduction in cell viability about 20%-60%), while nanocapsules with PLL/PGA coating did not evoke any detrimental effects on SH-SY5Y cells. Curcumin encapsulated in PLL/PGA showed similar neuroprotective activity against hydrogen peroxide (H2O2)-induced cell damage, as did 5 μM curcumin pre-dissolved in DMSO (about 16% of protection). Determination of concentration of curcumin in cell lysate confirmed that curcumin in nanocapsules has cell protective effect in lower concentrations (at least 20 times) than when given alone. Intracellular mechanisms of encapsulated curcumin-mediated protection engaged the prevention of the H2O2-induced decrease in mitochondrial membrane potential (MMP) but did not attenuate Reactive Oxygen Species (ROS) formation. The obtained results indicate the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity.

BMY 30047: A novel topically active retinoid with low local and systemic toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nair, X.; Quigley, J.; Tramposch, K.M.

In the treatment of various dermatological disorders, topically applied retinoids have potential therapeutic use with the advantage of improved localized activity and lower toxicity over systemically administered retinoids. However, most retinoids cause a significant degree of local irritation. In the present study, the ability to produce local activity with low local irritation potential was evaluated with a novel retinoic acid derivative. BMY 30047 (11-cis, 13-cis-12-hydroxymethylretinoic acid delta-lactone) is one of a series of retinoic acid derivatives in which the carboxyl function of the polar end was modified with the aim of achieving reduced local irritation and systemic toxicity while retainingmore » the local therapeutic effect. BMY 30047 was evaluated and compared with all-trans retinoic acid for topical retinoid activity in several preclinical assay systems, including the utricle reduction assay in rhino mice, 12-o-tetradecanoylphorbol 13-acetate ester-stimulated ornithine decarboxylase induction in hairless mice and the UV light-induced photodamaged skin model in hairless mice. BMY 30047 was assessed for retinoid-type side effects by evaluating the skin irritation potential in rabbits after repeated topical application, and hypervitaminosis A-inducing potential in mice after i.p. injection. BMY 30047 demonstrated significant topical retinoid activity in several in vivo models with less skin irritation potential relative to the most used clinical concentrations of all-trans retinoic acid. BMY 30047 also showed very little systemic activity and did not produce any evidence of hypervitaminosis A syndrome at systemic doses 20 times greater than the no-effect dose of all-trans retinoic acid.« less

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in mice.

PubMed

Roberts, L G; Gray, T M; Marr, M C; Tyl, R W; Trimmer, G W; Hoffman, G M; Murray, F J; Clark, C R; Schreiner, C A

2014-11-01

CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies. Exposure to 20,000mg/m(3) of BGVC produced slight reductions in maternal body weight/gain and decreased fetal body weight. G/MTBE exposure did not produce statistically significant maternal or developmental effects; however, two uncommon ventral wall closure defects occurred: gastroschisis (1 fetus at 10,000mg/m(3)) and ectopia cordis (1 fetus at 2000mg/m(3); 2 fetuses/1 litter at 10,000mg/m(3)). A second study (G/MTBE-2) evaluated similar exposure levels on GD 5-16 and an additional group exposed to 30,000mg/m(3) from GD 5-10. An increased incidence of cleft palate was observed at 30,000mg/m(3) G/MTBE. No ectopia cordis occurred in the replicate study, but a single observation of gastroschisis was observed at 30,000mg/m(3). The no observed adverse effect levels for maternal/developmental toxicity in the BGVC study were 10,000/2000mg/m(3), 20,000/20,000 for the G/MTBE study, and 10,000/20,000 for the G/MTBE-2 study. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Cost-Effectiveness of Tramadol and Oxycodone in the Treatment of Knee Osteoarthritis.

PubMed

Smith, Savannah R; Katz, Jeffrey N; Collins, Jamie E; Solomon, Daniel H; Jordan, Joanne M; Suter, Lisa G; Yelin, Edward H; David Paltiel, A; Losina, Elena

2017-02-01

To evaluate the cost-effectiveness of incorporating tramadol or oxycodone into knee osteoarthritis (OA) treatment. We used the Osteoarthritis Policy Model to evaluate long-term clinical and economic outcomes of knee OA patients with a mean age of 60 years with persistent pain despite conservative treatment. We evaluated 3 strategies: opioid-sparing (OS), tramadol (T), and tramadol followed by oxycodone (T+O). We obtained estimates of pain reduction and toxicity from published literature and annual costs for tramadol ($600) and oxycodone ($2,300) from Red Book Online. Based on published data, in the base case, we assumed a 10% reduction in total knee arthroplasty (TKA) effectiveness in opioid-based strategies. Outcomes included quality-adjusted life years (QALYs), lifetime cost, and incremental cost-effectiveness ratios (ICERs) and were discounted at 3% per year. In the base case, T and T+O strategies delayed TKA by 7 and 9 years, respectively, and led to reduction in TKA utilization by 4% and 10%, respectively. Both opioid-based strategies increased cost and decreased QALYs compared to the OS strategy. Tramadol's ICER was highly sensitive to its effect on TKA outcomes. Reduction in TKA effectiveness by 5% (compared to base case 10%) resulted in an ICER for the T strategy of $110,600 per QALY; with no reduction in TKA effectiveness, the ICER was $26,900 per QALY. When TKA was not considered a treatment option, the ICER for T was $39,600 per QALY. Opioids do not appear to be cost-effective in OA patients without comorbidities, principally because of their negative impact on pain relief after TKA. The influence of opioids on TKA outcomes should be a research priority. © 2016, American College of Rheumatology.

Reduction of hexavalent chromium by the thermophilic methanogen Methanothermobacter thermautotrophicus

NASA Astrophysics Data System (ADS)

Singh, Rajesh; Dong, Hailiang; Liu, Deng; Zhao, Linduo; Marts, Amy R.; Farquhar, Erik; Tierney, David L.; Almquist, Catherine B.; Briggs, Brandon R.

2015-01-01

Despite significant progress on iron reduction by thermophilic microorganisms, studies on their ability to reduce toxic metals are still limited, despite their common co-existence in high temperature environments (up to 70 °C). In this study, Methanothermobacter thermautotrophicus, an obligate thermophilic methanogen, was used to reduce hexavalent chromium. Experiments were conducted in a growth medium with H2/CO2 as substrate with various Cr6+ concentrations (0.2, 0.4, 1, 3, and 5 mM) in the form of potassium dichromate (K2Cr2O7). Time-course measurements of aqueous Cr6+ concentrations using 1,5-diphenylcarbazide colorimetric method showed complete reduction of the 0.2 and 0.4 mM Cr6+ solutions by this methanogen. However, much lower reduction extents of 43.6%, 13.0%, and 3.7% were observed at higher Cr6+ concentrations of 1, 3 and 5 mM, respectively. These lower extents of bioreduction suggest a toxic effect of aqueous Cr6+ to cells at this concentration range. At these higher Cr6+ concentrations, methanogenesis was inhibited and cell growth was impaired as evidenced by decreased total cellular protein production and live/dead cell ratio. Likewise, Cr6+ bioreduction rates decreased with increased initial concentrations of Cr6+ from 13.3 to 1.9 μM h-1. X-ray absorption near-edge structure (XANES) spectroscopy revealed a progressive reduction of soluble Cr6+ to insoluble Cr3+ precipitates, which was confirmed as amorphous chromium hydroxide by selected area electron diffraction pattern. However, a small fraction of reduced Cr occurred as aqueous Cr3+. Scanning and transmission electron microscope observations of M. thermautotrophicus cells after Cr6+ exposure suggest both extra- and intracellular chromium reduction mechanisms. Results of this study demonstrate the ability of M. thermautotrophicus cells to reduce toxic Cr6+ to less toxic Cr3+ and its potential application in metal bioremediation, especially at high temperature subsurface radioactive waste disposal sites, where the temperature may reach ∼70 °C.

Evaluation of the toxicity and antimicrobial activity of hydroethanolic extract of Arrabidaea chica (Humb. & Bonpl.) B. Verl.

PubMed

Mafioleti, Luciano; da Silva Junior, Iberê Ferreira; Colodel, Edson Moleta; Flach, Adriana; Martins, Domingos Tabajara de Oliveira

2013-11-25

Arrabidaea chica (Bignoniaceae) is a vine native to the Amazon Rainforest, popularly known as "crajiru" and whose infusion and decoction of the leaves are used to treat diseases such as gastric ulcers, inflammations, infections, anemia, herpes, jaundice among others. It is also used as a natural dye. This work aimed to evaluate the in vitro and in vivo toxicity, antimicrobial activity including analysis of chemical constitution of the hydroethanolic extract of the leaves of Arrabidaea chica (HEAc). Acute and subchronic toxicity of HEAc was evaluated in mice and rats, respectively, and by Alamar blue (cytotoxicity assay) using CHO-K1 cells. Antimicrobial activity of HEAc was tested by broth microdilution method using a panel of bacteria and yeast of clinical interest. The preliminary phytochemical analysis of HEAc was performed by electrospray ionization mass spectrometry [ESI(+)-MS]. Secondary metabolites were quantified by colorimetric methods. When administered in vivo at doses up to 3000 mg/kg v.o., HEAc did not cause any signs and symptoms of acute toxicity in mice and no cytotoxicity in CHO-K1 cells. Administration for 30 days caused leukocytosis (200 mg/kg) and reversible reductions in non-dose dependent of body weight, total weight gain and feed intake in rats given 200mg/kg and 500 mg/kg of HEAc, but were not accompanied by behavioral and clinical changes (laboratory and histopathological) that may have demonstrated evidences of subchronic toxicity HEAc demonstrated a pronounced activity against Helicobacter pylori (MIC=12.5 μg/mL) and moderate activity against Enterococcus faecalis (MIC=100 μg/mL) in broth microdilution. Preliminary phytochemical analysis of HEAc by colorimetric methods revealed that mainly the presence of phenolic compounds (16.6%), especially flavones and flavonols (4.02%). [ESI(+)-MS] fingerprint analyses of HEAc revealed the presence of 3-deoxyanthocyanidins and kaempferol. Our data provide evidence that HEAc is safe and can be useful in infections related to Helicobacter pylori and Enterococcus faecalis. Phytochemical analysis revealed the predominant presence of flavones and flavonols, possibly involved in the antimicrobial action of HEAc. © 2013 Elsevier Ireland Ltd. All rights reserved.

Solar light irradiation significantly reduced cytotoxicity and disinfection byproducts in chlorinated reclaimed water.

PubMed

Lv, Xiao-Tong; Zhang, Xue; Du, Ye; Wu, Qian-Yuan; Lu, Yun; Hu, Hong-Ying

2017-11-15

Chlorinated reclaimed water is widely used for landscaping and recreational purposes, resulting in human exposure to toxic disinfection byproducts. Although the quality of chlorinated reclaimed water might be affected by sunlight during storage, the effects of solar light irradiation on the toxicity remain unknown. This study investigated the changes in cytotoxicity and total organic halogen (TOX) of chlorinated reclaimed water exposed to solar light. Irradiation with solar light for 12 h was found to significantly reduce the cytotoxicity of chlorinated reclaimed water by about 75%, with ultraviolet light being responsible for the majority of this reduction. Chlorine residual in reclaimed water tended to increase the cytotoxicity, and the synergy between solar light and free chlorine could not enhance the reduction of cytotoxicity. Adding hydroxyl radical scavengers revealed that the contribution of hydroxyl radical to cytotoxicity reduction was limited. Solar light irradiation concurrently reduced TOX. The low molecular weight (<1 kDa) fraction was the major contributor of cytotoxicity and TOX in chlorinated reclaimed water. Detoxification of the low molecular weight fraction by light irradiation was mainly a result of TOX dehalogenation, while detoxification of the high molecular weight (>1 kDa) fraction was probably caused by photoconversion from high toxic TOX to low toxic TOX. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of antioxidants on vanadate-induced toxicity towards isolated perfused rat livers.

PubMed

Younes, M; Kayser, E; Strubelt, O

1991-01-01

The effect of trolox C, a water soluble vitamin E analogue, propyl gallate and ascorbate on vanadate hepatotoxicity was investigated in vitro. In isolated perfused livers from fasted rats, sodium orthovanadate (2 mmol/l) led to toxic responses including reduction of oxygen consumption, release of cytosolic (glutamate-pyruvate-transaminase (GPT) and lactate dehydrogenase (LDH)) and mitochondrial (glutamate-dehydrogenase (GLDH)) enzymes, intracellular accumulation of calcium, a marked depletion of glutathione (GSH) and an enhanced formation and release of thiobarbituric acid- (TBA) reactive material. Trolox C and propyl gallate inhibited the release of GPT and LDH partially and that of GLDH totally, but had no influence on vanadate-induced calcium accumulation or on the reduction of oxygen consumption. Both agents suppressed vanadate-induced lipid peroxidation (LPO) and partially prevented GSH depletion. Ascorbate failed to provide any protection probably due to the interference of its pro-oxidant potential with its antioxidant activity. The protection, mainly of mitochondria, afforded by those agents which also inhibited LPO substantiates our previous findings that the pro-oxidant activity of vanadate is mainly responsible for its direct hepatotoxic actions [2]. Besides, reduction of organ perfusion rate due to vasoconstriction also contributes to vanadate toxicity, but oxidative stress is not involved in this indirect toxic activity.

Oxidative degradation and toxicity reduction of trichloroethylene (TCE) in water using TiO2/solar light: comparative study of TiO2 slurry and immobilized systems.

PubMed

Cho, Il-Hyoung; Park, Jae-Hong; Kim, Young-Gyu

2005-01-01

A solar-driven, photocatalyzed degradation system using TiO2 slurry and immobilized systems was constructed and applied to the degradation of trichloroethylene (TCE) contaminated water using TiO2 with solar light. The experiments were carried out under constant weather conditions on a sunny day. Solar photocatalytic treatment efficiency of the solar light/TiO2 slurry system was compared with that of the solar light/TiO2 immobilized system. The operation of the solar light/TiO2 slurry and immobilized systems showed 100% (TiO2 slurry system), 80% (TiO2 immobilized system) degradation of the TCE after 6 h, with a chloride production yield of approximately 89% (TiO2 slurry system), 72% (TiO2 immobilized system). The oxidants such as H2O2 and S2O8(2-) in the TiO2 slurry and immobilized systems increased TCE degradation rate by suppressing the electron/hole recombination process. The degradation rate and relative toxicity reduction of TCE followed the order of solar light/TiO2 slurry + S2O8(2-) > solar light/TiO2 slurry + H2O2 > solar light/TiO2 immobilized + S2O8(2-) > solar light/TiO2 slurry > solar light/TiO2 immobilized + H2O2 > solar light/TiO2 immobilized. Finally, following to the toxicity result, the acute toxicity was reduced by below toxicity endpoint (EC50 concentration) following the treatment. It means that many of the metabolites of TCE reduction are less toxic to Vibrio fischeri than the parent compound. Based on these results, TCE can be efficiently and safely treated in a solar-driven, photocatalyzed degradation system.

Cholesterol is necessary both for the toxic effect of Abeta peptides on vascular smooth muscle cells and for Abeta binding to vascular smooth muscle cell membranes.

PubMed

Subasinghe, Supundi; Unabia, Sharon; Barrow, Colin J; Mok, Su San; Aguilar, Marie-Isabel; Small, David H

2003-02-01

Accumulation of beta amyloid (Abeta) in the brain is central to the pathogenesis of Alzheimer's disease. Abeta can bind to membrane lipids and this binding may have detrimental effects on cell function. In this study, surface plasmon resonance technology was used to study Abeta binding to membranes. Abeta peptides bound to synthetic lipid mixtures and to an intact plasma membrane preparation isolated from vascular smooth muscle cells. Abeta peptides were also toxic to vascular smooth muscle cells. There was a good correlation between the toxic effect of Abeta peptides and their membrane binding. 'Ageing' the Abeta peptides by incubation for 5 days increased the proportion of oligomeric species, and also increased toxicity and the amount of binding to lipids. The toxicities of various Abeta analogs correlated with their lipid binding. Significantly, binding was influenced by the concentration of cholesterol in the lipid mixture. Reduction of cholesterol in vascular smooth muscle cells not only reduced the binding of Abeta to purified plasma membrane preparations but also reduced Abeta toxicity. The results support the view that Abeta toxicity is a direct consequence of binding to lipids in the membrane. Reduction of membrane cholesterol using cholesterol-lowering drugs may be of therapeutic benefit because it reduces Abeta-membrane binding.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, Diane E.; Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA; Hoover, Benjamin

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6more » syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti-tumor activity of protease-activated anthrax toxins were evaluated. • All anthrax toxin variants exhibited potent systemic anti-tumor activity in mice. • A dual MMP/uPA-activated anthrax toxin displayed a superior safety profile. • Clinical development of a dual MMP/uPA-activated anthrax toxin is feasible.« less

Particle- and gas-phase PAHs toxicity equivalency quantity emitted by a non-road diesel engine with non-thermal plasma technology.

PubMed

Gao, Jianbing; Ma, Chaochen; Xing, Shikai; Zhang, Yajie; Liu, Jiangquan; Feng, Hao

2016-10-01

Polycyclic aromatic hydrocarbon (PAH) toxicity equivalency quantity (TEQ, denoted by benzo(a)pyrene equivalent (BaPeq) concentration) is more meaningful when evaluating the influence of non-road diesel engines PAH toxicity on environment. Particle- and gas-phase PAH BaPeq concentrations were calculated based on gas chromatography-mass spectrometer (GC-MS) results and toxic equivalency factors. A non-thermal plasma (NTP) reactor was applied to a non-road diesel engine to decrease PAH TEQ content. Only the gas-phase Nap BaPeq concentration increased slightly with the action of NTP at three different generator power outputs. BaP dominated the BaPeq concentration for 15 samples with, and without NTP except in the gas-phase at 4 kW. Almost all medium molecular weight (MMW) and high molecular weight (HMW) PAH TEQs increased for particle- and gas-phases at 3 kW power output compared to 2 kW without the use of NTP. Particle-phase Nap, Acp, and AcPy (low molecular weight, LMW) TEQ were under detection at 3 and 4 kW, while gas-phase BkF, IND, DBA, and BghiP (HMW) concentrations were below the limits of detection. The most abundant PAH TEQ compounds were MMW and HMW PAHs for gas- and particle-phase while they were BaA, CHR, BbF, BaP, and IND for PM aggregation. The total BaPeq emission factors were 15.1, 141.4, and 46.5 μg m(-3) at three engine loads, respectively. Significant BaPeq concentration percentage reduction was obtained (more than 80 and 60 %) with the use of NTP for particle- and gas-phases. A high TEQ content was observed for PM aggregation (38.8, 98.4, and 50.0 μg kg(-1)) which may have caused secondary PAH toxicity emissions. With the action of NTP, the breakup of MMW and HMW into LMW PAHs led to reduction of some PAH concentrations.

Assessing the effectiveness of chemical treatment with nanomaterials in improving the quality of different industrial effluents =

NASA Astrophysics Data System (ADS)

Nogueira, Veronica Ines Jesus Oliveira

Industrial activities are the major sources of pollution in all environments. Depending on the type of industry, various levels of organic and inorganic pollutants are being continuously discharged into the environment. Although, several kinds of physical, chemical, biological or the combination of methods have been proposed and applied to minimize the impact of industrial effluents, few have proved to be totally effective in terms of removal rates of several contaminants, toxicity reduction or amelioration of physical and chemical properties. Hence, it is imperative to develop new and innovative methodologies for industrial wastewater treatment. In this context nanotechnology arises announcing the offer of new possibilities for the treatment of wastewaters mainly based on the enhanced physical and chemical proprieties of nanomaterials (NMs), which can remarkably increase their adsorption and oxidation potential. Although applications of NMs may bring benefits, their widespread use will also contribute for their introduction into the environment and concerns have been raised about the intentional use of these materials. Further, the same properties that make NMs so appealing can also be responsible for producing ecotoxicological effects. In a first stage, with the objective of selecting NMs for the treatment of organic and inorganic effluents we first assessed the potential toxicity of nanoparticles of nickel oxide (NiO) with two different sizes (100 and 10-20 nm), titanium dioxide (TiO2, < 25 nm) and iron oxide (Fe2O3, ≈ 85x425 nm). The ecotoxicological assessment was performed with a battery of assays using aquatic organisms from different trophic levels. Since TiO2 and Fe2O3 were the NMs that presented lower risks to the aquatic systems, they were selected for the second stage of this work. Thus, the two NMs pre-selected were tested for the treatment of olive mill wastewater (OMW). They were used as catalyst in photodegradation systems (TiO2/UV, Fe2O3/UV, TiO2/H2O2/UV and Fe2O3/H2O2/UV). The treatments with TiO2 or Fe2O3 combined with H2O2 were the most efficient in ameliorating some chemical properties of the effluent. Regarding the toxicity to V. fischeri the highest reduction was recorded for the H2O2/UV system, without NMs. Afterwards a sequential treatment using photocatalytic oxidation with NMs and degradation with white-rot fungi was applied to OMW. This new approach increased the reduction of chemical oxygen demand, phenolic content and ecotoxicity to V. fischeri. However, no reduction in color and aromatic compounds was achieved after 21 days of biological treatment. The photodegradation systems were also applied to treat the kraft pulp mill and mining effluents. For the organic effluent the combination NMs and H2O2 had the best performances in reduction the chemical parameters as well in terms of toxicity reduction. However, for the mine effluent the best (TiO2/UV and Fe2O3/UV) were only able to significantly remove three metals (Zn, Al and Cd). Nonetheless the treatments were able of reducing the toxicity of the effluent. As a final stage, the toxicity of solid wastes formed during wastewater treatment with NMs was assessed with Chironomus riparius larvae, a representative species of the sediment compartment. Certain solid wastes showed the potential to negatively affect C. riparius survival and growth, depending on the type of effluent treated. This work also brings new insights to the use of NMs for the treatment of industrial wastewaters. Although some potential applications have been announced, many evaluations have to be performed before the upscaling of the chemical treatments with NMs.

Nano gold conjugation, anti-arthritic potential and toxicity studies of snake Naja kaouthia (Lesson, 1831) venom protein toxin NKCT1 in male albino rats and mice.

PubMed

Saha, Partha Pratim; Bhowmik, Tanmoy; Dasgupta, Anjan Kumar; Gomes, Antony

2014-08-01

Nanoscience and Nanotechnology have found their way in the fields of pharmacology and medicine. The conjugation of drug to nanoparticles combines the properties of both. In this study, gold nanoparticle (GNP) was conjugated with NKCT1, a cytotoxic protein toxin from Indian cobra venom for evaluation of anti-arthritic activity and toxicity in experimental animal models. GNP conjugated NKCT1 (GNP-NKCT1) synthesized by NaBH4 reduction method was stable at room temperature (25 +/- 2 degrees C), pH 7.2. Hydrodynamic size of GNP-NKCT1 was 68-122 nm. Arthritis was developed by Freund's complete adjuvant induction in male albino rats and treatment was done with NKCT1/GNP-NKCT1/standard drug. The paw/ankle swelling, urinary markers, serum markers and cytokines were changed significantly in arthritic control rats which were restored after GNP-NKCT1 treatment. Acute toxicity study revealed that GNP conjugation increased the minimum lethal dose value of NKCT1 and partially reduced the NKCT1 induced increase of the serum biochemical tissue injury markers. Histopathological study showed partial restoration of toxic effect in kidney tissue after GNP conjugation. Normal lymphocyte count in culture was in the order of GNP-NKCT1 > NKCT1 > Indomethacine treatment. The present study confirmed that GNP conjugation increased the antiarthritic activity and decreased toxicity profile of NKCT1.

Bioretention storm water control measures decrease the toxicity of copper roof runoff.

PubMed

LaBarre, William J; Ownby, David R; Rader, Kevin J; Lev, Steven M; Casey, Ryan E

2017-06-01

The present study evaluated the ability of 2 different bioretention storm water control measures (SCMs), planter boxes and swales, to decrease the toxicity of sheet copper (Cu) roofing runoff to Daphnia magna. The present study quantified changes in storm water chemistry as it passed through the bioretention systems and utilized the biotic ligand model (BLM) to assess whether the observed D. magna toxicity could be predicted by variations found in water chemistry. Laboratory toxicity tests were performed using select storm samples with D. magna cultured under low ionic strength conditions that were appropriate for the low ionic strength of the storm water samples being tested. The SCMs decreased toxicity of Cu roof runoff in both the BLM results and the storm water bioassays. Water exiting the SCMs was substantially higher than influent runoff in pH, ions, alkalinity, and dissolved organic carbon and substantially lower in total and dissolved Cu. Daphnids experienced complete mortality in untreated runoff from the Cu roof (the SCM influent); however, for planter and swale effluents, survival averaged 86% and 95%, respectively. The present study demonstrated that conventional bioretention practices, including planter boxes and swales, are capable of decreasing the risk of adverse effects from sheet Cu roof runoff to receiving systems, even before considering dilution of effluents in those receiving systems and associated further reductions in copper bioavailability. Environ Toxicol Chem 2017;36:1680-1688. © 2016 SETAC. © 2016 SETAC.

Toxic Overload: The Waste Disposal Dilemma.

ERIC Educational Resources Information Center

Knox, Robert J.

1991-01-01

The role of the Environmental Protection Agency as ombudsman concerning waste disposal is examined with respect to both the current options of source reduction and recycling as pollution prevention, and alternative approaches that expand upon these current options, particularly with respect to toxic and medical waste. (JJK)

USE OF TOXICITY IDENTIFICATION EVALUATION METHODS TO CHARACTERIZE IDENTIFY, AND CONFIRM HEXAVALENT CHROMIUM TOXICITY IN AN INDUSTRIAL EFFLUENT

EPA Science Inventory

A toxicity identification evaluation (TIE) was conducted on effluent from a major industrial discharger. Initial monitoring showed slight chronic toxicity to Ceriodaphnia dubia; later sample showed substantial toxicity to C. dubia. Chemical analysis detected hexavalent chromium ...

Prenatal and postnatal toxicity induced in guinea-pigs by nitrosomethylurea.

PubMed

Epstein, S S; Hasumi, K; Iobal, Z M

1976-01-01

Oral administration of NMU at maximally tolerated doses of guinea-pigs from day 34 to 58 of pregnancy induced embryotoxic effects, as evidenced by a high incidence of stillbirths and reduction in birth weight, and postnatal toxic effects, as evidenced by stunting, progressive mortality and extensive fatty degeneration of the liver in F1 progeny. Similar administration of NMUT at maximally tolerated doses did not induce such toxic effects.

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

PubMed

Sorenmo, Karin; Overley, B; Krick, E; Ferrara, T; LaBlanc, A; Shofer, F

2010-09-01

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

Toxicity evaluation of surface water treated with different disinfectants in HepG2 cells.

PubMed

Marabini, Laura; Frigerio, Silvia; Chiesara, Enzo; Radice, Sonia

2006-01-01

It is well known that water disinfection through chlorination causes the formation of a mixture of disinfection by-products (DBPs), many of which are genotoxic and carcinogenic. To demonstrate the formation of such compounds, a pilot water plant supplied with water from Lake Trasimeno was set up at the waterworks of Castiglione del Lago (PG, Italy). The disinfectants, continuously added to pre-filtered lake water flowing into three different basins, were sodium hypochlorite, chlorine dioxide and peracetic acid, an alternative disinfectant used until now for disinfecting waste waters, but not yet studied for a possible use in drinking water treatment. The aim of this study was to evaluate the formation during the disinfection processes of some toxic compounds that could explain the genotoxic effects of drinking waters. Differently treated waters were concentrated by solid-phase adsorption on silica C(18) columns and toxicity was assessed in a line of human hepatoma cells (HepG2), a metabolically competent cellular line very useful for human risk evaluation. The seasonal variability of the physical-chemical water characteristics (AOX, UV 254 nm, potential formation of THM, pH and temperature) made indispensable experimentation with water samples taken during the various seasons. Autumn waters cause greater toxicity compared to those of other seasons, in particular dilution of the concentrate at 0.5l equivalent of disinfected waters with chlorine dioxide and peracetic acid causes a 55% reduction in cellular vitality while the cellular vitality is over 80% with the all other water concentrates. Moreover it is very interesting underline that non-cytotoxic quantities of the autumnal water concentrates cause, after 2h treatment, a decrease in GSH and a statistically significant increase in oxygen radicals, while after prolonged treatment (24h) cause a GSH increase, without variations in the oxygen radical content. This phenomenon could be interpreted as the cellular adaptation response to an initial oxidative stress.

Silver nanoparticles toxicity against airborne strains of Staphylococcus spp.

PubMed

Wolny-Koładka, Katarzyna A; Malina, Dagmara K

2017-11-10

The aim of this study was to explore the toxicity of silver nanoparticles (AgNPs) synthesized by chemical reduction method assessment with regard to airborne strains of Staphylococcus spp. The first step of the experiment was the preparation of silver nanoparticle suspension. The suspension was obtained by a fast and simple chemical method involving the reduction of silver ions through a reducing factor in the presence of the suitable stabilizer required to prevent the aggregation. In the second stage, varied instrumental techniques were used for the analysis and characterization of the obtained nanostructures. Third, the bacteria of the Staphylococcus genus were isolated from the air under stable conditions with 47 sports and recreational horses, relatively. Next, isolated strains were identified using biochemical and spectrophotometric methods. The final step was the evaluation of the Staphylococcus genus sensitivity to nanosilver using the disk diffusion test. It has been proven that prepared silver nanoparticles exhibit strong antibacterial properties. The minimum inhibitory concentration for tested isolates was 30 μg/mL. It has been found that the sensitivity of Staphylococcus spp. isolated from six identified species differs considerably. The size distribution of bacterial growth inhibition zones indicates that resistance to various nanosilver concentrations is an individual strain feature, and has no connection with belonging to a specific species.

Environmental implications on the oxygenation of gasoline with ethanol in the metropolitan area of Mexico City.

PubMed

Schifter, I; Vera, M; Díaz, L; Guzmán, E; Ramos, F; López-Salinas, E

2001-05-15

Motor vehicle emission tests were performed on 12 in-use light duty vehicles, made up of the most representative emission control technologies in Mexico City: no catalyst, oxidative catalyst, and three way catalyst. Exhaust regulated (CO, NOx, and hydrocarbons) and toxic (benzene, formaldehyde, acetaldehyde, and 1,3-butadiene) emissions were evaluated for MTBE (5 vol %)- and ethanol (3, 6, and 10 vol %)-gasoline blends. The most significant overall emissions variations derived from the use of 6 vol % ethanol (relative to a 5% MTBE base gasoline) were 16% decrease in CO, 28% reduction in formaldehyde, and 80% increase in acetaldehyde emissions. A 26% reduction in CO emissions from the oldest fleet (< MY 1991, without catalytic converter), which represents about 44% of the in-use light duty vehicles in Mexico city, can be attained when using 6 vol% ethanol-gasoline, without significant variation in hydrocarbons and NOx emissions, when compared with a 5% vol MTBE-gasoline. On the basis of the emissions results, an estimation of the change in the motor vehicle emissions of the metropolitan area of Mexico city was calculated for the year 2010 if ethanol were to be used instead of MTBE, and the outcome was a considerable decrease in all regulated and toxic emissions, despite the growing motor vehicle population.

Multi-walled Carbon Nanotubes Reduce Toxicity of Diphenhydramine to Ceriodaphnia dubia in Water and Sediment Exposures.

PubMed

Myer, Mark H; Black, Marsha C

2017-09-01

Multi-walled carbon nanotubes are adsorptive materials that have potential for remediation of organic contaminants in water. Sediment elutriate exposures were undertaken with Ceriodaphnia dubia to compare the toxic effects of diphenhydramine in the presence and absence of sediment and multi-walled carbon nanotubes. In both sediment and solution-only treatments, addition of 0.318 mg/g of carbon nanotubes significantly decreased 48-h mortality relative to control, with a 78.7%-90.1% reduction in treatments with nanotube-amended sediment and 40.7%-53.3% reduction in nanotube-amended water exposures. The greatest degree of relative mortality reduction occurred in sediments containing higher levels of natural organic matter, indicating a potential additive effect.

Evaluation of two mycotoxin binders to reduce toxicity of broiler diets containing ochratoxin A and T-2 toxin contaminated grain.

PubMed

García, A R; Avila, E; Rosiles, R; Petrone, V M

2003-01-01

In order to assess ochratoxin A (OA) and T-2 toxin (T-2) binding ability of two commercial sorbents, both in vitro and in vivo trials with broilers were performed. Crude OA and T-2 extracts from contaminated grain were used to assess in vitro binding ability of two sorbents (Zeotek [Zk] and Mycofix [Mx]), by quantifying free mycotoxin through an enzyme-linked immunosorbent assay (ELISA) test. For in vivo trial, a 3 x 2 x 2 factorial arrangement was used for this experiment, being the factors: adsorbents (none, Zk, and Mx), OA (0 and 567 parts per billion [ppb]) and T-2 (0 and 927 ppb). OA and T-2 contaminated wheat and corn, respectively, were added to sorghum-soybean meal diets to meet 567 ppb of OA and 927 ppb of T-2. Mycotoxins were fed alone or combined in treatments. After 21 days, blood chemistry, gross, and histological evaluations were performed. Relative weights of liver, kidney, and bursa of Fabricius were obtained. Zk had the highest OA and T-2 in vitro binding ability (100% and 8.67%, respectively). Chickens fed OA with or without sorbents had a lower body weight and feed intake reduction. However, those birds fed T-2 were partly protected by a sorbent. Birds fed both toxins showed toxic additive effects, and no protection of any adsorbent was observed. A significant reduction in plasma proteins, albumin, and globulins was a characteristic observed in all birds fed diets with OA both with or without adsorbents. Uric acid level in blood was increased in all chickens fed OA-contaminated diets. Histological findings observed in birds fed OA-contaminated diets were necrosis of kidney tubular cells, swollen and necrotic hepatocytes, bile ducts hyperplasia, and increased diameter of proventriculus glands. In birds that received T-2 alone, only the liver, with the same kind of lesions, was affected. According to these results, it can be concluded that there is not a relation between in vitro and in vivo trials. OA toxic effects could not be counteracted by any sorbent. T-2 toxicity could be partially counteracted by an adsorbent used in this research.

Toxicity of iron overload and iron overload reduction in the setting of hematopoietic stem cell transplantation for hematologic malignancies.

PubMed

Leitch, Heather A; Fibach, Eitan; Rachmilewitz, Eliezer

2017-05-01

Iron is an essential element for key cellular metabolic processes. However, transfusional iron overload (IOL) may result in significant cellular toxicity. IOL occurs in transfusion dependent hematologic malignancies (HM), may lead to pathological clinical outcomes, and IOL reduction may improve outcomes. In hematopoietic stem cell transplantation (SCT) for HM, IOL may have clinical importance; endpoints examined regarding an impact of IOL and IOL reduction include transplant-related mortality, organ function, infection, relapse risk, and survival. Here we review the clinical consequences of IOL and effects of IOL reduction before, during and following SCT for HM. IOL pathophysiology is discussed as well as available tests for IOL quantification including transfusion history, serum ferritin level, transferrin saturation, hepcidin, labile plasma iron and other parameters of iron-catalyzed oxygen free radicals, and organ IOL by imaging. Data-based recommendations for IOL measurement, monitoring and reduction before, during and following SCT for HM are made. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluating the acute effects of oral, non-combustible potential reduced exposure products marketed to smokers

PubMed Central

Cobb, CO; Weaver, MF; Eissenberg, T

2011-01-01

Background Non-combustible potential reduced exposure products (PREPs; eg, Star Scientific’s Ariva; a variety of other smokeless tobacco products) are marketed to reduce the harm associated with smoking. This marketing occurs despite an absence of objective data concerning the toxicant exposure and effects of these PREPs. Methods used to examine combustible PREPs were adapted to assess the acute effects of non-combustible PREPs for smokers. Methods 28 overnight abstinent cigarette smokers (17 men, 14 non-white) each completed seven, Latin-squared ordered, approximately 2.5 h laboratory sessions that differed by product administered: Ariva, Marlboro Snus (Philip Morris, USA), Camel Snus (RJ Reynolds, Winston-Salem, North Carolina, USA), Commit nicotine lozenge (GlaxoSmithKline; 2 mg), own brand cigarettes, Quest cigarettes (Vector Tobacco; delivers very low levels of nicotine) and sham smoking (ie, puffing on an unlit cigarette). In each session, the product was administered twice (separated by 60 min), and plasma nicotine levels, expired air CO and subjective effects were assessed regularly. Results Non-combustible products delivered less nicotine than own brand cigarettes, did not expose smokers to CO and failed to suppress tobacco abstinence symptoms as effectively as combustible products. Conclusions While decreased toxicant exposure is a potential indicator of harm reduction potential, a failure to suppress abstinence symptoms suggests that currently marketed non-combustible PREPs may not be a viable harm reduction strategy for US smokers. This study demonstrates how clinical laboratory methods can be used to evaluate the short-term effects of non-combustible PREPs for smokers. PMID:19346218

Use of ozone in a pilot-scale plant for textile wastewater pre-treatment: physico-chemical efficiency, degradation by-products identification and environmental toxicity of treated wastewater.

PubMed

Somensi, Cleder A; Simionatto, Edésio L; Bertoli, Sávio L; Wisniewski, Alberto; Radetski, Claudemir M

2010-03-15

In this study, ozonation of raw textile wastewater was conducted in a pilot-scale plant and the efficiency of this treatment was evaluated based on the parameters color removal and soluble organic matter measured as chemical oxygen demand (COD), at two pH values (9.1 and 3.0). Identification of intermediate and final degradation products of ozone pre-treatment, as well as the evaluation of the final ecotoxicity (Lumistox test) of pre-treated wastewater, was also carried out. After 4h of ozone treatment with wastewater recirculation (flow rate of 0.45 m(3)h(-1)) the average efficiencies for color removal were 67.5% (pH 9.1) and 40.6% (pH 3.0), while COD reduction was 25.5% (pH 9.1) and 18.7% (pH 3.0) for an ozone production capacity of 20 g h(-1). Furthermore, ozonation enhances the biodegradability of textile wastewater (BOD(5)/COD ratios) by a factor of up to 6.8-fold. A GC-MS analysis of pre-treated textile wastewater showed that some products were present at the end of the pre-treatment time. In spite of this fact, the bacterial luminescence inhibition test (Lumistox test) showed a significant toxicity reduction on comparing the raw and treated textile wastewater. In conclusion, pre-ozonation of textile wastewater is an important step in terms of improving wastewater biodegradability, as well as reducing acute ecotoxicity, which should be removed completely through sequential biological treatment. (c) 2009. Published by Elsevier B.V.

Epidermal growth factor receptor-tyrosine kinase inhibitors for non-small-cell lung cancer patients aged 80 years or older: A retrospective analysis

PubMed Central

NAKAO, MAKOTO; MURAMATSU, HIDEKI; SONE, KAZUKI; AOKI, SACHIKO; AKIKO, HARATA; KAGAWA, YUSUKE; SATO, HIDEFUMI; KUNIEDA, TAKEFUMI

2015-01-01

The efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in elderly patients with non-small-cell lung cancer (NSCLC) remains uncertain. This retrospective study aimed to evaluate the efficacy and feasibility of EGFR-TKIs for NSCLC patients aged ≥ 80 years. We analyzed data from 21 NSCLC patients aged ≥ 80 years who were administered gefitinib and/or erlotinib between January, 2009 and December, 2014. The clinical characteristics, smoking status, type of EFGR mutation and the efficacy and toxicity of EGFR-TKIs were evaluated in these patients. In total, 14 (66.7%), 5 (23.8%) and 2 patients (9.5%) displayed partial response, stable disease and progressive disease, respectively. The median progression-free survival was 182 days, whereas the median overall survival was 371 days. Adverse events ≥ grade 2 were as follows: skin toxicities, 12 patients; liver function test abnormalities, 7 patients; anorexia, 3 patients; and diarrhea, 2 patients. Dose reduction of EGFR-TKIs due to adverse events was required in 15 patients (71.4%). Although gefitinib and erlotinib therapy may be beneficial in patients aged ≥ 80 years, EGFR-TKI dose modification may be necessary according to the overall medical condition of elderly patients. Further studies are required to evaluate our findings. PMID:25798276

Toxicological evaluation of ethanolic extract from Stevia rebaudiana Bertoni leaves: Genotoxicity and subchronic oral toxicity.

PubMed

Zhang, Qiannan; Yang, Hui; Li, Yongning; Liu, Haibo; Jia, Xudong

2017-06-01

Stevia rebaudiana Bertoni leaves have a long history of use as an abundant source of sweetener. The aqueous extract of stevia leaves and the predominant constitutes steviol glycosides have been intensively investigated. However, rare studies provided toxicological evaluation of bioactive components in the polar extract regarding their safety on human health. This study aimed to evaluate the toxicity of ethanolic extract of Stevia rebaudiana Bertoni leaves through a battery of in vitro and in vivo tests. Negative results were unanimously obtained from bacterial reverse mutation assay, mouse bone marrow micronucleus assay and mouse sperm malformation assay. Oral administration at dietary levels of 1.04%, 2.08% and 3.12% for 90 days did not induce significant behavioral, hematological, clinical, or histopathological changes in rats. Significant reduction of cholesterol, total protein and albumin was observed in female animals only at high dose level. The results demonstrated that Stevia rebaudiana Bertoni leaves ethanolic extract, which is rich in isochlorogenic acids, does not possess adverse effects through oral administration in this study. Our data provided supportive evidence for the safety of Stevia rebaudiana Bertoni leaves that may potentially be used in functional foods as well as nutritional supplements beyond sweetner. Copyright © 2017 Elsevier Inc. All rights reserved.

The percutaneous toxicokinetics of Sulphur mustard in a damaged skin porcine model and the evaluation of WoundStat™ as a topical decontaminant.

PubMed

Hall, Charlotte A; Lydon, Helen L; Dalton, Christopher H; Chipman, J Kevin; Graham, John S; Chilcott, Robert P

2017-09-01

This study used a damaged skin, porcine model to evaluate the in vivo efficacy of WoundStat™ for decontamination of superficial (non-haemorrhaging), sulphur mustard-contaminated wounds. The dorsal skin of 12 female pigs was subjected to controlled physical damage and exposed to 10 μL 14 C-radiolabelled sulphur mustard ( 14 C-SM). Animals were randomly assigned to either a control or a treatment group. In the latter, WoundStat™ was applied 30 s post exposure and left in situ for 1 h. Skin lesion progression and decontaminant efficacy were quantified over 6 h using a range of biophysical measurements. Skin, blood and organ samples were taken post mortem for histopathological assessment, 14 C-SM distribution and toxicokinetic analyses. Application of SM to damaged skin without decontamination was rapidly followed by advanced signs of toxicity, including ulceration and decreased blood flow at the exposure site in all animals. WoundStat™ prevented ulceration and improved blood flow at the exposure site in all decontaminated animals (n = 6). Furthermore, significantly smaller quantities of 14 C-SM were detected in the blood (45% reduction), and recovered from skin (70% reduction) and skin surface swabs (99% reduction) at 6 h post-challenge. Overall, the distribution of 14 C-SM in the internal organs was similar for both groups, with the greatest concentration in the kidneys, followed by the liver and small intestine. WoundStat™ significantly reduced the amount of 14 C-SM recovered from the liver, a key organ for SM metabolism and detoxification. This study demonstrates that WoundStat™ is a suitable product for reducing the ingress and toxicity of a chemical warfare agent. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Dan; Wu, Chun-qi; Li, Ze-jun

Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrialmore » respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for hepatotoxicity.« less

Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity.

PubMed

Carchia, E; Porreca, I; Almeida, P J; D'Angelo, F; Cuomo, D; Ceccarelli, M; De Felice, M; Mallardo, M; Ambrosino, C

2015-10-29

Epidemiologic and experimental studies have associated changes of blood glucose homeostasis to Bisphenol A (BPA) exposure. We took a toxicogenomic approach to investigate the mechanisms of low-dose (1 × 10(-9 )M) BPA toxicity in ex vivo cultures of primary murine pancreatic islets and hepatocytes. Twenty-nine inhibited genes were identified in islets and none in exposed hepatocytes. Although their expression was slightly altered, their impaired cellular level, as a whole, resulted in specific phenotypic changes. Damage of mitochondrial function and metabolism, as predicted by bioinformatics analyses, was observed: BPA exposure led to a time-dependent decrease in mitochondrial membrane potential, to an increase of ROS cellular levels and, finally, to an induction of apoptosis, attributable to the bigger Bax/Bcl-2 ratio owing to activation of NF-κB pathway. Our data suggest a multifactorial mechanism for BPA toxicity in pancreatic islets with emphasis to mitochondria dysfunction and NF-κB activation. Finally, we assessed in vitro the viability of BPA-treated islets in stressing condition, as exposure to high glucose, evidencing a reduced ability of the exposed islets to respond to further damages. The result was confirmed in vivo evaluating the reduction of glycemia in hyperglycemic mice transplanted with control and BPA-treated pancreatic islets. The reported findings identify the pancreatic islet as the main target of BPA toxicity in impairing the glycemia. They suggest that the BPA exposure can weaken the response of the pancreatic islets to damages. The last observation could represent a broader concept whose consideration should lead to the development of experimental plans better reproducing the multiple exposure conditions.

Lethal and sublethal toxicity of the industrial chemical epichlorohydrin on Rhinella arenarum (Anura, Bufonidae) embryos and larvae.

PubMed

Hutler Wolkowicz, Ianina R; Aronzon, Carolina M; Pérez Coll, Cristina S

2013-12-15

Lethal and sublethal toxicity of the major chemical used in epoxide compounds, epichlorohydrin (ECH) was evaluated on the early life cycle of the common South American toad, Rhinella arenarum (Anura, Bufonidae). The stages evaluated were (according to Del Conte and Sirlin): early blastula (S.3-S.4), gastrula (S.10-S.12), rotation (S.15), tail bud (S.17), muscular response (S.18), gill circulation (S.20), open mouth (S.21), opercular folds (S.23) and complete operculum (S.25). The LC50 and EC50 values for lethal and sublethal effects were calculated. The early blastula was the most sensitive stage to ECH both for continuously and pulse-exposures (LC50-24h=50.9 mg L(-1)), while S.20 was the most resistant (LC50-24h=104.9 mg L(-1)). Among sublethal effects, early blastula was also the most sensitive stage (LOEC-48 h=20 mg L(-1)) and it has a Teratogenic Index of 2.5, which indicates the teratogenic potential of the substance. The main abnormalities were persistent yolk plugs, cell dissociation, tumors, hydropsy, oral malformations, axial/tail flexures, delayed development and reduced body size. ECH also caused neurotoxicity including scarce response to stimuli, reduction in the food intake, general weakness, spasms and shortening, erratic or circular swimming. Industrial contamination is considered an important factor on the decline of amphibian populations. Considering the available information about ECH's toxicity and its potential hazard to the environment, this work shows the first results of its developmental toxicity on a native amphibian species, Rhinella arenarum. Copyright © 2013 Elsevier B.V. All rights reserved.

Toxicological interactions between mycotoxins from ubiquitous fungi: Impact on hepatic and intestinal human epithelial cells.

PubMed

Sobral, M Madalena C; Faria, Miguel A; Cunha, Sara C; Ferreira, Isabel M P L V O

2018-07-01

Aflatoxin B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1) and ochratoxin A (OTA) are toxic fungal metabolites co-occurring naturally in the environment. This study aimed to evaluate the toxicological interactions of these mycotoxins concerning additive, antagonistic and synergistic toxicity towards human cells. The theoretical biology-based Combination index-isobologram method was used to evaluate the individual and binary effect of these toxins and determine the type of the interaction using as models Caco-2 (intestinal) and HepG2 (hepatic) cells. Cytotoxicity was assessed using the MTT test at the concentrations of 0.625-20 μM for all the compounds. DON exerted the highest toxicity toward both cells, OTA and AFB1 also showed a dose-effect response, whereas no toxicity was verified for FB1. Synergism or antagonism effects occurred when exposing AFB1-DON and AFB1-OTA on Caco-2 cells at higher or lower concentrations, respectively; while DON-OTA showed synergism throughout all inhibition levels. Concerning HepG2, AFB1-DON exerted a strong synergism, regardless of the level; whereas AFB1-OTA had slight synergism/nearly additive effect; and, OTA-DON had a moderate antagonism/nearly additive effect. Synergistic strengths as high as a dose reduction index of 10 for AFB1-DON were observed in hepatic cells. Taken together our findings indicate that the toxicological effects differ regarding the type of mycotoxins used for combinations and the stronger synergistic effect was observed for mixtures containing DON in both cells. Therefore, even though DON has not been classified as to its carcinogenicity to humans, this mycotoxin may present a serious threat to health, mainly when co-occurring in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of weathering on ecopersistence, reactivity, and potential toxicity of naturally occurring asbestos and asbestiform minerals.

PubMed

Enrico Favero-Longo, Sergio; Turci, Francesco; Tomatis, Maura; Compagnoni, Roberto; Piervittori, Rosanna; Fubini, Bice

2009-01-01

The mechanisms underlying asbestos toxicity mainly rely on experiments performed on "laboratory" fibers, but little data is available on naturally occurring asbestos (NOA). Human exposure to NOA is subject to their ecopersistence and the modulation of their potential toxicity following weathering. The effect of weathering on three fibrous minerals from the Italian Western Alps, chrysotile, tremolite, and balangeroite-a Fe-rich asbestiform mineral-was investigated by mimicking more than 100 yr of physical (freezing-thawing/wetting-drying cycles in a climatic chamber) and biochemical forces (incubation with oxalic acid). Ion release, evaluated by means of inductively coupled plasma-atomic emission spectroscopy (ICP-AES), and variation in chemical composition, evaluated by scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS), indicated that weathering modified the fibers in the series: chrysotile > balangeroite > tremolite. Kinetics of ion release from the fibers (Mg, Fe, and Si) revealed different ion removal pathways. Tremolite was poorly affected. Chrysotile preferentially released cations up to a plateau, with physical and biochemical forces acting competitively. Conversely, for balangeroite, upon which weathering forces acted synergistically, the initial loss of ions facilitated further dissolution and more Si than Mg was released, suggesting an ongoing collapse of the crystal structure. Depletion of redox-reactive ions produced a significant reduction in fiber-derived *OH radicals (EPR, spin-trapping technique), but the fibrous nature was always retained. Despite weathered fibers appearing less toxic than "stored/laboratory" ones, NOA is to be considered far from safe because of fibrous nature and residual surface reactivity. Risk assessment needs to consider the effect of weathering on exposures. Both tremolite and balangeroite may contaminate, in some areas, chrysotile asbestos. However, in contrast to tremolite, balangeroite exhibits a low ecopersistence, similar to chrysotile behavior. Any contribution of balangeroite to chrysotile toxicity will thus be related to its quantitative occurrence and not to higher structural stability.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities.

PubMed

Peters, Diane E; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A; Leppla, Stephen H; Bugge, Thomas H

2014-09-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5-3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. Published by Elsevier Inc.

Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

PubMed Central

Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

2014-01-01

We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; Mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA- activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32%–87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. PMID:24971906

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

PubMed

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.

Risk Reduction from Minimization of Persistent, Bioaccumulative, and Toxic Waste Materials Within the U.S. Industrial Solid Waste Management System

EPA Science Inventory

This study addressed three questions of interest in national-scale solid and hazardous waste management decision-making within the United States: 1) can we quantify the reduction in risk to human and ecological receptors resulting from the reduction of certain industrial waste s...

The Massachusetts Toxics Use Reduction Act: a model for nanomaterials regulation?

NASA Astrophysics Data System (ADS)

Nash, Jennifer

2012-08-01

Nanomaterials exemplify a new class of emerging technologies that have significant economic and social value, pose uncertain health and environmental risks, and are entering the marketplace at a rapid pace. Effective regimes for regulating emerging technologies generate information about known or suspected hazards and draw on private sector expertise to guide managers' behavior toward risk reduction, even in the absence of clear evidence of harm. This paper considers the extent to which the federal Toxic Substances Control Act (TSCA) accomplishes those objectives. It offers the approach of the Massachusetts Toxics Use Reduction Act (TURA) as a possible supplement to TSCA, filling gaps in agency knowledge and private sector capacities. TURA is notable for its focus on chemicals use and hazard and its emphasis on strengthening firms' internal management systems. Given the current deadlock in Congressional efforts to modernize federal laws such as TSCA, the role of state laws like TURA merit attention. Absent definitive information about risk, a governance strategy that generates information and focuses management attention on reducing hazards is worth considering.

Oral Chromium Exposure and Toxicity

PubMed Central

Sun, Hong; Brocato, Jason

2015-01-01

Hexavalent chromium [Cr(VI)] is a known carcinogen when inhaled. However, inhalational exposure to Cr(VI) affects only a small portion of the population, mainly by occupational exposures. In contrast, oral exposure to Cr(VI) is widespread and affects many people throughout the globe. In 2008, the National Toxicology Program (NTP) released a 2-year study demonstrating that ingested Cr(VI) was carcinogenic in rats and mice. The effects of Cr(VI) oral exposure is mitigated by reduction in the gut, however a portion evades the reductive detoxification and reaches target tissues. Once Cr(VI) enters the cell, it ultimately gets reduced to Cr(III), which mediates its toxicity via induction of oxidative stress during the reduction while Cr intermediates react with protein and DNA. Cr(III) can form adducts with DNA that may lead to mutations. This review will discuss the potential adverse effects of oral exposure to Cr(VI) by presenting up-to-date human and animal studies, examining the underlying mechanisms that mediate Cr(VI) toxicity, as well as highlighting opportunities for future research. PMID:26231506

USE OF POWDERED COCONUT CHARCOAL AS A TOXICITY IDENTIFICATION AND EVALUATION MANIPULATION FOR ORGANIC TOXICANTS IN MARINE SEDIMENTS

EPA Science Inventory

We report on a procedure using powdered coconut charcoal to sequester organic contaminants and reduce toxicity in sediments as part of a series of toxicity identification and evaluation (TIE) methods. Powdered coconut charcoal (PCC) was effective in reducing the toxicity of endos...

Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents.

PubMed

Stoica, Sonia; Magoulas, George E; Antoniou, Antonia I; Suleiman, Sherif; Cassar, Analisse; Gatt, Lucienne; Papaioannou, Dionissios; Athanassopoulos, Constantinos M; Schembri-Wismayer, Pierre

2016-02-15

Activation of minoxidil (MNX) with N,N'-carbonyldiimidazole and coupling with natural polyamines (PAs) and commercially available aliphatic or aromatic amines provided a series of new conjugates which were evaluated for their ability to induce differentiation to HL-60 acute myeloid leukemia cancer cells, using a modified NBTZ reduction test. Although neither MNX nor 4,4'-methylenedianiline (MDA) or 2,7-diaminofluorene (DAF), alone or in combination, had any effect, the MNX-spermine (SPM) conjugate (11) and the conjugates 7 and 8 of MNX with MDA and DAF exhibited a differentiation-inducing effect at a concentration of 10 μM without being toxic on proliferating human peripheral blood mononuclear cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

GLUT2 in pancreatic islets: crucial target molecule in diabetes induced with multiple low doses of streptozotocin in mice.

PubMed

Wang, Z; Gleichmann, H

1998-01-01

In mice, diabetes can be induced by multiple low doses of streptozotocin (MLD-STZ), i.e., 40 mg/kg body wt on each of 5 consecutive days. In this model, diabetes develops only when STZ induces both beta-cell toxicity and T-cell-dependent immune reactions. The target molecule(s) of MLD-STZ-induced beta-cell toxicity are not known, however. In this study, we report that GLUT2 is a target molecule for MLD-STZ toxicity. Ex vivo, a gradual decrement of both GLUT2 protein and mRNA expression was found in pancreatic islets isolated from MLD-STZ-treated C57BL/6 male mice, whereas mRNA expression of beta-actin, glucokinase, and proinsulin remained unaffected. Significant reduction of both GLUT2 protein and mRNA expression was first noted 1 day after the third STZ injection, clearly preceding the onset of hyperglycemia. The extent of reduction increased with the number of STZ injections administered and increased over time, after the last, i.e., fifth, STZ injection. The STZ-induced reduction of GLUT2 protein and mRNA was not due to an essential loss of beta-cells, because ex vivo, not only the total RNA yield and protein content in isolated islets, but also proinsulin mRNA expression, failed to differ significantly in the differently treated groups. Furthermore, islets isolated from MLD-STZ-treated donors responded to the nonglucose secretagogue arginine in a pattern similar to that of solvent-treated donors. Interestingly, the MLD-STZ-induced reduction of both GLUT2 protein and mRNA was prevented by preinjecting mice with 5-thio-D-glucose before each STZ injection. Apparently, GLUT2 is a crucial target molecule of MLD-STZ toxicity, and this toxicity seems to precede the immune reactions against beta-cells.

Excretory nitrogen metabolism and defence against ammonia toxicity in air-breathing fishes.

PubMed

Chew, S F; Ip, Y K

2014-03-01

With the development of air-breathing capabilities, some fishes can emerge from water, make excursions onto land or even burrow into mud during droughts. Air-breathing fishes have modified gill morphology and morphometry and accessory breathing organs, which would tend to reduce branchial ammonia excretion. As ammonia is toxic, air-breathing fishes, especially amphibious ones, are equipped with various strategies to ameliorate ammonia toxicity during emersion or ammonia exposure. These strategies can be categorized into (1) enhancement of ammonia excretion and reduction of ammonia entry, (2) conversion of ammonia to a less toxic product for accumulation and subsequent excretion, (3) reduction of ammonia production and avoidance of ammonia accumulation and (4) tolerance of ammonia at cellular and tissue levels. Active ammonia excretion, operating in conjunction with lowering of ambient pH and reduction in branchial and cutaneous NH₃ permeability, is theoretically the most effective strategy to maintain low internal ammonia concentrations. NH₃ volatilization involves the alkalization of certain epithelial surfaces and requires mechanisms to prevent NH₃ back flux. Urea synthesis is an energy-intensive process and hence uncommon among air-breathing teleosts. Aestivating African lungfishes detoxify ammonia to urea and the accumulated urea is excreted following arousal. Reduction in ammonia production is achieved in some air-breathing fishes through suppression of amino acid catabolism and proteolysis, or through partial amino acid catabolism leading to alanine formation. Others can slow down ammonia accumulation through increased glutamine synthesis in the liver and muscle. Yet, some others develop high tolerance of ammonia at cellular and tissue levels, including tissues in the brain. In summary, the responses of air-breathing fishes to ameliorate ammonia toxicity are many and varied, determined by the behaviour of the species and the nature of the environment in which it lives. © 2014 The Fisheries Society of the British Isles.

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balmuri, Sricharani Rao

Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH){sub 2} without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare themore » toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd{sup 2+} ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd{sup 2+} ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd{sup 2+} from sources such as cigarette smoke. - Highlights: • Toxicity of CdO nanoparticles can be mitigated by the use of sodium citrate. • Sodium citrate covers the CdO surface and reduces Cd{sup 2+} ion release. • Use of sodium citrate reduces both biochemical and histopathological changes. • Sodium citrate can be a remediation strategy against CdO nanoparticles toxicity.« less

Mechanistic Approach to Understanding the Toxicity of the Azole Fungicide Triadimefon to a Nontarget Aquatic Insect and Implications for Exposure Assessment

EPA Science Inventory

We utilized mechanistic and stereoselective based in vitro metabolism assays and sublethal exposures of triadimefon to gain insight into the extent of carbonyl reduction and the toxic mode of action of triadimefon with black fly (Diptera: Simuliidae) larvae.

EXAMINATION OF QUINONE TOXICITY USING YEAST SACCHAROMYCES CEREVISIAE MODEL SYSTEM. (R827352C007)

EPA Science Inventory

The toxicity of quinones is generally thought to occur by two mechanisms: the formation of covalent bonds with biological molecules by Michael addition chemistry and the catalytic reduction of oxygen to superoxide and other reactive oxygen species (ROS) (redox cycling). In an ...

Profiling the activity of environmental chemicals in prenatal developmental toxicity studies using the U.S. EPA’s ToxRefDB

EPA Science Inventory

As the primary source for regulatory developmental toxicity information, prenatal studies characterize maternal effects and fetal endpoints including malformations, resorptions, and fetal weight reduction. Results from 383 rat and 368 rabbit prenatal studies on 387 chemicals, mo...

Spirulina exhibits hepatoprotective effects against lead induced oxidative injury in newborn rats.

PubMed

Gargouri, M; Ben Saad, H; Ben Amara, I; Magné, C; El Feki, A

2016-08-31

Lead is a toxic metal that induces a wide range of biochemical and physiological effects. The present investigation was designed at evaluating the toxic effects of a prenatal exposure to lead of mothers on hepatic tissue of newborn rats, and potent protective effects of spirulina. Female rats were randomly divided into 4 groups which were given a normal diet (control),a diet enriched with spirulina (S), lead acetate administered through drinking water (Pb), or a diet enriched with spirulina and lead contaminated water (S Pb), respectively. The duration of treatments was from the 5th day of gestation to 14 days postpartum. Lead toxicity was assessed by measuring body and liver weights, blood and stomach lead levels, hepatic DNA, RNA and protein amounts, blood enzyme activities (AST and ALT), as well as lipid peroxidation level and activities of antioxidant enzymes in hepatic tissues of neonates. Lead intoxication of mothers caused reduction of liver weight as well as of hepatic DNA, mRNA and protein levels in newborns. Moreover, oxidative stress and changes in antioxidant enzyme activities were recorded. Conversely, supplementation of mothers with spirulina mitigated these effects induced by lead. These results substantiated the potential hepatoprotective and antioxidant activity of spirulina.

Comparative alternative materials assessment to screen toxicity hazards in the life cycle of CIGS thin film photovoltaics.

PubMed

Eisenberg, Daniel A; Yu, Mengjing; Lam, Carl W; Ogunseitan, Oladele A; Schoenung, Julie M

2013-09-15

Copper-indium-gallium-selenium-sulfide (CIGS) thin film photovoltaics are increasingly penetrating the market supply for consumer solar panels. Although CIGS is attractive for producing less greenhouse gas emissions than fossil-fuel based energy sources, CIGS manufacturing processes and solar cell devices use hazardous materials that should be carefully considered in evaluating and comparing net environmental benefits of energy products. Through this research, we present a case study on the toxicity hazards associated with alternative materials selection for CIGS manufacturing. We applied two numeric models, The Green Screen for Safer Chemicals and the Toxic Potential Indicator. To improve the sensitivity of the model outputs, we developed a novel, life cycle thinking based hazard assessment method that facilitates the projection of hazards throughout material life cycles. Our results show that the least hazardous CIGS solar cell device and manufacturing protocol consist of a titanium substrate, molybdenum metal back electrode, CuInS₂ p-type absorber deposited by spray pyrolysis, ZnS buffer deposited by spray ion layer gas reduction, ZnO:Ga transparent conducting oxide (TCO) deposited by sputtering, and the encapsulant polydimethylsiloxane. Copyright © 2013 Elsevier B.V. All rights reserved.

Ameliorative effect of curcumin on aflatoxin-induced toxicity in DNA, RNA and protein in liver and kidney of mice.

PubMed

Mathuria, Neeta; Verma, Ramtej Jayram

2007-01-01

The present investigation is an attempt to evaluate the ameliorative effect of curcumin on aflatoxin-induced toxicity in liver and kidney of mice. Aflatoxin was obtained by growing Aspergillus parasiticus in SMKY liquid medium. 70 male mice were divided into 7 groups (37-40 g body weight) including untreated control, vehicle control (0.2 mL olive oil/animal/day), curcumin control (50 mg/kg body weight/animal), aflatoxin low dose and high dose (750 and 1500 mg/kg body weight). Other two groups were administered curcumin along with low dose aflatoxin and high dose aflatoxin. The treatment was given for 45 days. On 46th day the animals were sacrificed by cervical dislocation. Liver and kidney were removed and weighed. Homogenates were prepared and analyzed for DNA, RNA and protein content. The results revealed dose-dependent significant reduction in DNA, RNA and protein contents in the liver and kidney of mice. Oral administration of aflatoxin along with curcumin significantly ameliorates, as compared to aflatoxin alone treated groups, in all parameters. It is concluded that curcumin ameliorates aflatoxin-induced toxicity in liver and kidney of mice.

Assessment of cytogenetic and cytotoxic effects of chlorhexidine digluconate on cultured human lymphocytes.

PubMed

Arabaci, Taner; Türkez, Hasan; Çanakçi, Cenk Fatih; Özgöz, Mehmet

2013-09-01

The aim of this study was to assess the genetic and cellular toxicity of Chlorhexidine digluconate (CHX) on peripheral human lymphocytes in vitro. Micronucleus assay was used to investigate the genotoxicity, while the cell viability and proliferation were evaluated by Trypan blue exclusion test and Nuclear Division Index in control and CHX-treated (0.05, 0.1, 0.2, 0.4, 0.5 mg/ml) human blood cultures. A dose-dependent toxic effect was found depending on CHX incubation on the genetic and cell viability of the lymphocytes. Micronucleus frequency was found to be statistically higher at 0.5 mg/ml concentration compared to lower doses and the control group (p < 0.05). A significant reduction was shown in the cell viability and cell proliferation of the exposed lymphocytes at the concentrations of 0.4 and 0.5 mg/ml (p < 0.05), while no significant toxicity was found at lower concentrations compared to control (p > 0.05). This study showed dose-dependent genotoxic and cytotoxic effects of CHX on human lymphocytes in vitro. It should be considered during periodontal irrigation or novel CHX products at lower concentrations should be manufactured for clinical usage.

Effects of Fungicides on Aquatic Fungi and Bacteria

NASA Astrophysics Data System (ADS)

Conners, D. E.; Rosemond, A. D.; Black, M. C.

2005-05-01

Aquatic microorganisms play an important role in conditioning leaf litter that enters streams and serves as an important base of production for consumers. Contamination of streams by fungicides may adversely affect microorganisms and alter leaf litter processing rates. Unfortunately, microorganisms are rarely used in acute toxicity tests for fungicide evaluation and registration. We adapted the resazurin reduction assay, which is used in medical microbiology, to assess the acute toxicity of four fungicides (azoxystrobin, trifloxystrobin, kresoxim-methyl and chlorothalonil) to aquatic fungi (Articulospora tetracladia) and bacteria (Cytophaga spp.), and investigated the ability of the toxicants to inhibit leaf breakdown in microcosms. Fungi were more sensitive to fungicides than many standard test organisms (cladocerans, green algae, trout), while bacteria were often the least sensitive. All of the fungicides except kresoxim-methyl, when added to microcosms at concentrations that inhibited the fungi by 90 percent in acute tests, reduced leaf breakdown rates by an average of 14.7 percent. Thus, aquatic fungi and their associated functions in streams may be relatively sensitive to fungicides applied terrestrially that enter streams through non-point sources. These data highlight the importance of including aquatic fungi in safety assessments of pesticides for protection of microbial function.

Acoustically active lipospheres containing paclitaxel: a new therapeutic ultrasound contrast agent.

PubMed

Unger, E C; McCreery, T P; Sweitzer, R H; Caldwell, V E; Wu, Y

1998-12-01

Paclitaxel-carrying lipospheres (MRX-552) were developed and evaluated as a new ultrasound contrast agent for chemotherapeutic drug delivery. Paclitaxel was suspended in soybean oil and added to an aqueous suspension of phospholipids in vials. The headspace of the vials was replaced with perfluorobutane gas; the vials were sealed, and they were agitated at 4200 rpm on a shaking device. The resulting lipospheres containing paclitaxel were studied for concentration, size, acute toxicity in mice, and acoustic activity and drug release with ultrasound. Lipospheres containing sudan black dye were produced to demonstrate the acoustically active liposphere (AAL)-ultrasound release concept. Acoustically active lipospheres containing paclitaxel had a mean particle count of approximately 1 x 10(9) particles per mL and a mean size of 2.9 microns. Acute toxicity studies in mice showed a 10-fold reduction in toxicity for paclitaxel in AALs compared with free paclitaxel. The AALs reflected ultrasound as a contrast agent. Increasing amounts of ultrasound energy selectively ruptured the AALs and released the paclitaxel. Acoustically active lipospheres represent a new class of acoustically active drug delivery vehicles. Future studies will assess efficacy of AALs for ultrasound-mediated drug delivery.

Nanosilica and Polyacrylate/Nanosilica: A Comparative Study of Acute Toxicity

PubMed Central

Niu, Ying-Mei; Zhu, Xiao-Li; Chang, Bing; Tong, Zhao-Hui; Cao, Wen; Qiao, Pei-Huan; Zhang, Lin-Yuan; Zhao, Jing; Song, Yu-Guo

2016-01-01

We compared the acute toxicity of nanosilica and polyacrylate/nanosilica instillation in Wistar rats (n = 60). Exposure to nanosilica and polyacrylate/nanosilica showed a 30% mortality rate. When compared with saline-treated rats, animals in both exposure groups exhibited a significant reduction of PO2 (P < 0.05) at both 24 and 72 hr. after exposure. Both exposure groups exhibited a significant reduction of neutrophils in arterial blood compared to saline controls (P < 0.05) 24 hr. after exposure. The levels of blood ALT and LDH in exposed groups were found to be significantly increased (P < 0.05) 24 hr. following exposure. The exposed groups exhibited various degrees of pleural effusion and pericardial effusion. Our findings indicated respiratory exposure to polyacrylate/nanosilica and nanosilica is likely to cause multiple organ toxicity. PMID:26981538

Interaction of silver nanoparticles with biological objects: antimicrobial properties and toxicity for the other living organisms

NASA Astrophysics Data System (ADS)

Egorova, E. M.

2011-04-01

This paper presents several examples of the biological effects of small-sized silver nanoparticles (10.5±3.5nm) observed in experiments on bacteria, slim mold, unicellular alga and plant seeds. The nanoparticles were prepared by the biochemical synthesis, based on the reduction of metal ions in reverse vicelles by biological reductants - natural plant pigments (flavonoids). It is found that, except for the plant seeds, silver nanoparticles (SNP) act as a strong toxic agent, both in water solution and as part of liquid-phase material. It is shown also that the biological action of silver nanoparticles can not be reduced to the toxic action of silver ions in equivalent concentrations or to that of the surfactant (the SNP stabilizer) present in the SNP water solution. Possible SNP applications are suggested.

Phase I study of indicine N-oxide in patients with advanced cancer.

PubMed

Ohnuma, T; Sridhar, K S; Ratner, L H; Holland, J F

1982-07-01

Indicine N-oxide is a pyrrolizidine alkaloid isolated from Heliotropium indicum, one of the widely used herbs in Ayurvedic medicine. Thirty-seven patients with solid tumors received the drug: 15 men and 22 women (mean age, 53 years). All had had prior chemotherapy, and 25 had had prior radiotherapy. Eighty-four percent had a performance status of 0-3 (Cancer and Leukemia Group B criteria). The drug was given as a short infusion over 15 minutes and repeated with a median interval of 4 weeks. Doses were escalated from 1 to 9 g/m2. A total of 55 courses were evaluable. Dose-limiting toxic effects were leukopenia and thrombocytopenia, and the toxicity was cumulative with repeated doses. Other toxic effects included nausea and vomiting, anemia, and hepatic dysfunction. The hematologic toxicity tended to be more pronounced in patients with hepatic dysfunction, poor marrow reserve, and heavy prior chemotherapy and radiotherapy. There were no complete or partial responses. One patient with skin melanoma and another with ovarian carcinoma had improvement lasting 2 months. The maximally tolerated dose is 9 g/m2 in our population. A recommended dose for therapeutic study is 7 g/m2. High-risk patients should be started at a dose of 5 g/m2. The treatment may be repeated at 4-week intervals with close monitoring of wbc and platelet counts. Dose reductions may be necessary for repeated courses.

Palladium Nanoparticles Induce Disturbances in Cell Cycle Entry and Progression of Peripheral Blood Mononuclear Cells: Paramount Role of Ions

PubMed Central

Clemente, Emanuela; Di Giampaolo, Luca; Mariani-Costantini, Renato; Leopold, Kerstin; Schindl, Roland; Lotti, Lavinia V.; Sabbioni, Enrico; Niu, Qiao; Di Gioacchino, Mario

2014-01-01

There is concern about the possible toxicity of palladium nanoparticles (Pd-NP), as they are released in the environment through many applications. We previously studied the toxicity of Pd-NP at high concentrations; here we address the possible toxicity of Pd-NP at low, subtoxic doses. In particular, we have exposed normal human PBMC entering into the first in vitro mitotic division to Pd-NP and to Pd(IV) ions to evaluate ROS generation and cell cycle progression. We have measured a statistically significant increase of intracellular ROS in Pd(IV) exposed cells, but not in Pd-NP exposed cells. TEM revealed accumulation of lipid droplets and autophagic and mitophagic vacuoles, which appeared more conspicuous in cells exposed to Pd(IV) ions than to Pd-NP. Pd-NP were visible in the cytoplasm of Pd-NP exposed cells. Pd-NP addition was associated with a significant increase of cells within the G0/G1-phase and a significant reduction in GS- and G2/M-phases. Cells exposed to Pd(IV) ions showed a significant amplification of these cell cycle alterations. These results suggest that ions, per se or released by NPs, are the true inducers of Pd toxicity. It will be essential to verify whether the observed disturbance represents a temporary response or might result in permanent alterations. PMID:25105151

The impact of pesticide regulations on suicide in Sri Lanka

PubMed Central

Gunnell, D; Fernando, R; Hewagama, M; Priyangika, WDD; Konradsen, F; Eddleston, M

2010-01-01

Summary Background Between 1950 and 1995 suicide rates in Sri Lanka increased eight fold to a peak of 47 per 100,000 in 1995. By 2005 rates had halved. Our aim was to evaluate whether Sri Lanka’s regulatory controls on the import and sale of pesticides that are particularly toxic to humans were responsible for these changes in suicide. Methods Ecological analysis using graphical and descriptive approaches to identify times trends in suicide and risk factors for suicide in Sri Lanka, 1975-2005. Results Restrictions on the import and sales of WHO Class I toxicity pesticides in 1995 and endosulfan in 1998, coincided with reductions in suicide in both men and women of all ages. 19,800 fewer suicides occurred in 1996-2005 compared to 1986 – 1995. Secular trends in unemployment, alcohol misuse, divorce, pesticide use and the years associated with Sri Lanka’s Civil war did not appear to be associated with these declines. Conclusion These data indicate that in countries where pesticides are commonly used in acts of self-poisoning, import controls on the most toxic pesticides may have a favourable impact on suicide. In Asia there are an estimated 300,000 deaths from pesticide self-poisoning annually. National and international policies restricting the sales of pesticides that are most toxic to humans may have a major impact on suicides in the region. PMID:17726039

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy.

PubMed

Lin, Amy M; Rini, Brian I; Weinberg, Vivian; Fong, Kristen; Ryan, Charles J; Rosenberg, Jonathan E; Fong, Lawrence; Small, Eric J

2006-10-01

To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy. Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly. In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity. Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.

Decomposition byproducts induced by gamma radiation and their toxicity: the case of 2-nitrophenol.

PubMed

Alsager, Omar A; Basfar, Ahmed A; Muneer, Majid

2018-04-01

The induced degradation and detoxification of 2-nitrophenol (2-NP) in aqueous media by gamma irradiation were carefully evaluated in this study. Gamma radiation at absorbed doses as low as 20 kGy was able to degrade 2-NP to reach a removal of at least 85% across the investigated range of concentration (50-150 ppm). 2-NP breaks down to aromatic-based compounds with increasing number of byproducts upon increasing the radiation treatment from the absorbed dose of 50% decomposition (D 50 ) to the absorbed dose of 90% decomposition (D 90 ), after which no byproducts could be detected, indicating the formation of undetectable aliphatic hydrocarbons, insoluble, or volatile byproducts. Toxicology studies showed that the degradation of 2-NP under absorbed doses up to D 90 resulted in a more toxic byproduct than the parent compound, and a remarkable reduction in the toxicity was observed with the irradiated samples with absorbed doses above D 90 . Varying the pH of the media to acidic or basic conditions did not significantly alter the degradation behavior of 2-NP. However, a notable improvement of the detoxification was associated with the samples of acidic pH. Adding 0.5% of H 2 O 2 to 2-NP solutions had a positive effect by reducing D 90 by a factor of nine and diminishing the toxicity by twofolds.

Dechlorination kinetics of TCE at toxic TCE concentrations: Assessment of different models.

PubMed

Haest, P J; Springael, D; Smolders, E

2010-01-01

The reductive dechlorination of trichloroethene (TCE) in a TCE source zone can be self-inhibited by TCE toxicity. A study was set up to examine the toxicity of TCE in terms of species specific degradation kinetics and microbial growth and to evaluate models that describe this self-inhibition. A batch experiment was performed using the TCE dechlorinating KB-1 culture at initial TCE concentrations ranging from 0.04mM to saturation (8.4mM). Biodegradation activity was highest at 0.3mM TCE and no activity was found at concentrations from 4 to 8mM. Species specific TCE and cis-DCE (cis-dichloroethene) degradation rates and Dehalococcoides numbers were modeled with Monod kinetics combined with either Haldane inhibition or a log-logistic dose-response inhibition on these rates. The log-logistic toxicity model appeared the most appropriate model and predicts that the species specific degradation activities are reduced by a factor 2 at about 1mM TCE, respectively cis-DCE. However, the model showed that the inhibitive effects on the time for TCE to ethene degradation are a complex function of degradation kinetics and the initial cell densities of the dechlorinating species. Our analysis suggests that the self-inhibition on biodegradation cannot be predicted by a single concentration threshold without information on the cell densities.

Cyclodextrin Enhances Corneal Tolerability and Reduces Ocular Toxicity Caused by Diclofenac

PubMed Central

Abdelkader, Hamdy; Fathalla, Zeinab; Moharram, Hossam; Ali, Taha F. S.

2018-01-01

With advances in refractive surgery and demand for cataract removal and lens replacement, the ocular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased. One of the most commonly used NSAIDs is diclofenac (Diclo). In this study, cyclodextrins (CDs), α-, β-, γ-, and HP-β-CDs, were investigated with in vitro irritation and in vivo ulceration models in rabbits to reduce Diclo toxicity. Diclo-, α-, β-, γ-, and HP-β-CD inclusion complexes were prepared and characterized and Diclo-CD complexes were evaluated for corneal permeation, red blood cell (RBCs) haemolysis, corneal opacity/permeability, and toxicity. Guest- (Diclo-) host (CD) solid inclusion complexes were formed only with β-, γ-, and HP-β-CDs. Amphipathic properties for Diclo were recorded and this surfactant-like functionality might contribute to the unwanted effects of Diclo on the surface of the eye. Contact angle and spreading coefficients were used to assess Diclo-CDs in solution. Reduction of ocular toxicity 3-fold to16-fold and comparable corneal permeability to free Diclo were recorded only with Diclo-γ-CD and Diclo-HP-β-CD complexes. These two complexes showed faster healing rates without scar formation compared with exposure to the Diclo solution and to untreated groups. This study also highlighted that Diclo-γ-CD and Diclo-HP-β-CD demonstrated fast healing without scar formation. PMID:29636847

Lithium toxicity in plants: Reasons, mechanisms and remediation possibilities - A review.

PubMed

Shahzad, Babar; Tanveer, Mohsin; Hassan, Waseem; Shah, Adnan Noor; Anjum, Shakeel Ahmad; Cheema, Sardar Alam; Ali, Iftikhar

2016-10-01

Lithium (Li) is a naturally occurring element; however, it is one of the non-essential metals for life. Lithium is becoming a serious matter of discussion for the people who do research on trace metals and environmental toxicity in plants. Due to limited information available regarding its mobility from soil to plants, the adverse effects of Li toxicity to plants are still unclear. This article briefly discusses issues around Li, its role and its essentiality in plants and research directions that may assist in inter-disciplinary studies to evaluate the importance of Li's toxicity. Further, potential remediation approaches will also be highlighted in this review. Briefly, Li influenced the growth of plants in both stimulation and reduction ways, depending on the concentration of Li in growth medium. On the negative side, Li reduces the plant growth by interrupting numerous physiological processes and altering metabolism in plant. The contamination of soil by Li is becoming a serious problem, which might be a threat for crop production in the near future. Additionally, lack of considerable information about the tolerance mechanisms of plants further intensifies the situation. Therefore, future research should emphasize in finding prominent and approachable solutions to minimize the entry of Li from its sources (especially from Li batteries) into the soil and food chain. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Estimating genetic potential of biofuel forest hardwoods to withstand metal toxicity in industrial effluent under dry tropical conditions.

PubMed

Manzoor, S A; Mirza, S N; Zubair, M; Nouman, W; Hussain, S B; Mehmood, S; Irshad, A; Sarwar, N; Ammar, A; Iqbal, M F; Asim, A; Chattha, M U; Chattha, M B; Zafar, A; Abid, R

2015-08-14

Biofuel tree species are recognized as a promising alternative source of fuel to conventional forms. Additionally, these tree species are also effective in accumulating toxic heavy metals present in some industrial effluents. In developing countries such as Pakistan, the use of biofuel tree species is gaining popularity not only for harvesting economical and environmentally friendly biofuel, but also to sequester poisonous heavy metals from industrial wastewater. This study was aimed at evaluating the genetic potential of two biofuel species, namely, Jatropha curcas and Pongamia pinnata, to grow when irrigated with industrial effluent from the Pak-Arab Fertilizer Factory Multan, Southern Punjab, Pakistan. The growth performances of one-year-old seedlings of both species were compared in soil with adverse physiochemical properties. It was found that J. curcas was better able to withstand the toxicity of the heavy metals present in the fertilizer factory effluent. J. curcas showed maximum gain in height, diameter, and biomass production in soil irrigated with 75% concentrated industrial effluent. In contrast, P. pinnata showed a significant reduction in growth in soil irrigated with more than 50% concentrated industrial effluent, indicating that this species is less tolerant to higher toxicity levels of industrial effluent. This study identifies J. curcas as a promising biofuel tree species that can be grown using industrial wastewater.

In vitro and environmental toxicity of reduced graphene oxide as an additive in automotive lubricants.

PubMed

Esquivel-Gaon, Margarita; Nguyen, Nhung H A; Sgroi, Mauro F; Pullini, Daniele; Gili, Flavia; Mangherini, Davide; Pruna, Alina Iuliana; Rosicka, Petra; Sevcu, Alena; Castagnola, Valentina

2018-04-05

Despite the ground-breaking potential of nanomaterials, their safe and sustainable incorporation into an array of industrial markets prompts a deep and clear understanding of their potential toxicity for both humans and the environment. Among the many materials with great potential, graphene has shown promise in a variety of applications; however, the impact of graphene based products on living systems remains poorly understood. In this paper, we illustrate that via exploiting the tribological properties of graphene nanosheets, we can successfully improve both the frictional behaviour and the anti-wear capacity of lubricant oil for mechanical transmission. By virtue of reducing friction and enhancing lubricant lifetimes, we can forecast a reduction in friction based energy loss, in addition to a decrease in the carbon footprint of vehicles. The aforementioned positive environmental impact is further strengthened considering the lack of acute toxicity found in our extensive in vitro investigation, in which both eukaryotic and prokaryotic cells were tested. Collectively, our body of work suggests that by the use of safe nanoadditives we could contribute to reducing the environmental impact of transportation and therein take a positive step towards a more sustainable automotive sector. The workflow proposed here for the evaluation of human and environmental toxicity will allow for the study of nanosized bare graphene material and can be broadly applied to the translation of graphene-based nanomaterials into the market.

Parathion degradation and toxicity reduction in solar photocatalysis and photolysis.

PubMed

Zoh, K D; Kim, T S; Kim, J G; Choi, K; Yi, S M

2006-01-01

The solar photocatalytic degradation of methyl parathion was investigated using a circulating TiO2/solar light reactor. Under solar photocatalysis condition, parathion was more effectively degraded than solar photolysis and TiO2-only conditions. With solar photocatalysis, 20 mg/L of parathion was completely degraded within 60 min with a TOC decrease of 63% after 150 min. The main ionic byproducts during photocatalysis recovered from parathion degradation were mainly as NO3-, NO2- and NH4+, 80% of the sulphur as SO4(2-), and 5% of phosphorus as PO4(3-). The organic intermediates 4-nitrophenol and methyl paraoxon were also identified, and these were further degraded in solar photocatalytic condition. Two different bioassays (Vibrio fischeri and Daphnia magna) were used to test the acute toxicity of solutions treated by solar photocatalysis and photolysis. The Microtox test using V. fischeri showed that the toxicity expressed as EC50 (%) value increased from 5.5% to >82% in solar photocatalysis, indicating that the treated solution is non-toxic, but only increased from 4.9 to 20.5% after 150 min in solar photolysis. The acute toxicity test using D. magna showed that EC50 (%) increased from 0.05 to 1.08% under solar photocatalysis, but only increased to 0.12% after 150 min with solar photolysis, indicating the solution is still toxic. The pattern of toxicity reduction parallels the decrease in TOC and the parathion concentrations.

Single- and mixture toxicity of three organic UV-filters, ethylhexyl methoxycinnamate, octocrylene, and avobenzone on Daphnia magna.

PubMed

Park, Chang-Beom; Jang, Jiyi; Kim, Sanghun; Kim, Young Jun

2017-03-01

In freshwater environments, aquatic organisms are generally exposed to mixtures of various chemical substances. In this study, we tested the toxicity of three organic UV-filters (ethylhexyl methoxycinnamate, octocrylene, and avobenzone) to Daphnia magna in order to evaluate the combined toxicity of these substances when in they occur in a mixture. The values of effective concentrations (ECx) for each UV-filter were calculated by concentration-response curves; concentration-combinations of three different UV-filters in a mixture were determined by the fraction of components based on EC 25 values predicted by concentration addition (CA) model. The interaction between the UV-filters were also assessed by model deviation ratio (MDR) using observed and predicted toxicity values obtained from mixture-exposure tests and CA model. The results from this study indicated that observed ECx mix (e.g., EC 10mix , EC 25mix , or EC 50mix ) values obtained from mixture-exposure tests were higher than predicted ECx mix (e.g., EC 10mix , EC 25mix , or EC 50mix ) values calculated by CA model. MDR values were also less than a factor of 1.0 in a mixtures of three different UV-filters. Based on these results, we suggest for the first time a reduction of toxic effects in the mixtures of three UV-filters, caused by antagonistic action of the components. Our findings from this study will provide important information for hazard or risk assessment of organic UV-filters, when they existed together in the aquatic environment. To better understand the mixture toxicity and the interaction of components in a mixture, further studies for various combinations of mixture components are also required. Copyright © 2016 Elsevier Inc. All rights reserved.

The use of the zebrafish (Danio rerio) embryo for the acute toxicity testing of surfactants, as a possible alternative to the acute fish test.

PubMed

Vaughan, Martin; van Egmond, Roger

2010-06-01

At present, the acute toxicity of chemicals to fish is most commonly estimated by means of a short-term test on juvenile or adult animals (OECD TG 203). Although, over the last few years, the numbers used have been reduced due to the implementation of the Three Rs (Reduction, Refinement and Replacement), significant numbers of fish are still used in acute toxicity tests. With the introduction of the new European Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) system, this number is likely to increase dramatically. The aim of this work was to test the acute toxicity of a number of anionic, cationic and non-ionic surfactants to embryos of the zebrafish (Danio rerio), over 48 hours, as a possible alternative to the standard 96-hour fish acute test. We measured the toxicities of 15 surfactants, and compared the results to previously generated adult D. rerio LC50 data (or other fish species, if these data were not available). Comparison of the LC50 data showed that embryos appear to be as sensitive to cationic and non-ionic surfactants as the adult fish, but possibly are more sensitive to anionic surfactants. Toxicity testing with the embryo test can be carried out more quickly than with the adult test, uses much less space and media, requires less effort, and therefore can be performed at a reduced cost. The embryo test may also uncover additional sub-lethal effects, although these were not observed for surfactants. The data presented here show that the 48-hour embryo test can be considered as a suitable alternative to the adult acute fish test for surfactants.

The effect of temperature on the toxicity of insecticides against Musca domestica L.: implications for the effective management of diarrhea.

PubMed

Khan, Hafiz Azhar Ali; Akram, Waseem

2014-01-01

Diarrhea is an important cause of childhood mortality in developing countries like Pakistan because of unhygienic conditions, lack of awareness, and unwise use of preventive measures. Mechanical transmission of diarrheal pathogens by house flies, Musca domestica, is believed as the most effective route of diarrhea transmission. Although the use of insecticides as a preventive measure is common worldwide for the management of house flies, success of the measure could be compromised by the prevailing environmental temperature since it significantly affects toxicity of insecticides and thus their efficacy. Peaks of the house fly density and diarrheal cases are usually coincided and season specific, yet little is known about the season specific use of insecticides. To determine the temperature-toxicity relationship in house flies, the effect of post-bioassays temperature (range, 20-34°C) on the toxicity of seven insecticides from organophosphate (chlorpyrifos, profenofos), pyrethroid (cypermethrin, deltamethrin) and new chemical (emamectin benzoate, fipronil, spinosad) classes was evaluated by using a feeding bioassay method. From 20-34°C, the toxicities of chlorpyrifos, profenofos, emamectin and fipronil increased 2.10, 2.93, 2.40 and 3.82 fold (i.e. positive temperature coefficient), respectively. Whereas, the toxicities of cypermethrin, deltamethrin and spinosad decreased 2.21, 2.42 and 3.16 fold (i.e. negative temperature coefficient), respectively. These findings suggest that for the reduction in diarrheal cases, house flies should be controlled with insecticides according to the prevailing environmental temperature. Insecticides with a positive temperature coefficient may serve as potential candidates in controlling house flies and diarrhea epidemics in hot season and vice versa.

Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

PubMed

Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

2016-01-01

The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacogenetics of toxicity of 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients

PubMed Central

Tecza, Karolina; Pamula-Pilat, Jolanta; Lanuszewska, Joanna; Butkiewicz, Dorota; Grzybowska, Ewa

2018-01-01

The differences in patients’ response to the same medication, toxicity included, are one of the major problems in breast cancer treatment. Chemotherapy toxicity makes a significant clinical problem due to decreased quality of life, prolongation of treatment and reinforcement of negative emotions associated with therapy. In this study we evaluated the genetic and clinical risk factors of FAC chemotherapy-related toxicities in the group of 324 breast cancer patients. Selected genes and their polymorphisms were involved in FAC drugs transport (ABCB1, ABCC2, ABCG2,SLC22A16), metabolism (ALDH3A1, CBR1, CYP1B1, CYP2C19, DPYD, GSTM1, GSTP1, GSTT1, MTHFR,TYMS), DNA damage recognition, repair and cell cycle control (ATM, ERCC1, ERCC2, TP53, XRCC1). The multifactorial risk models that combine genetic risk modifiers and clinical characteristics were constructed for 12 toxic symptoms. The majority of toxicities was dependent on the modifications in components of more than one pathway of FAC drugs, while the impact level of clinical factors was comparable to the genetic ones. For the carriers of multiple high risk factors the chance of developing given symptom was significantly elevated which proved the factor-dosage effect. We found the strongest associations between concurrent presence of clinical factors - overall and recurrent anemia, nephrotoxicity and early nausea and genetic polymorphisms in genes responsible for DNA repair, drugs metabolism and transport pathways. These results indicate the possibility of selection of the patients with expected high tolerance to FAC treatment and consequently with high chance of chemotherapy completion without the dose reduction, treatment delays and decline in the quality of life. PMID:29507678

Evaluation of General Toxicity, Anti-Oxidant Activity and Effects of Ficus Carica Leaves Extract on Ischemia/Reperfusion Injuries in Isolated Heart of Rat

PubMed Central

Allahyari, Saeideh; Delazar, Abbas; Najafi, Moslem

2014-01-01

Purpose: This study was aimed to evaluate general toxicity, anti-oxidant activity and effects of Ficus carica leaves extract on ischemia/reperfusion injuries. Methods: Antioxidant activity, total phenolic and flavonoid compounds of 70% methanolic extract of Ficus carica leaves were measured. The general toxicity test was carried out by brine shrimp lethality assay. Isolated hearts of male rats were mounted on a Langendorff apparatus and perfused with modified Krebs-Henseleit solution. In control group, the hearts were perfused with normal Krebs solution, however, treatment groups received enriched solution with the extract (0.04, 0.2 and 1 mg/ml) during stabilization and reperfusion (after 30 min global ischemia), respectively. Cardiac arrhythmias were analyzed and TTC method was used for infarct size determination. Results: The extract displayed antioxidant activity in the DPPH assay (RC50=0.06666 mg/ml). Total phenolic content was 12.29 mg GAE/100 g dry sample and the amount of flavonoids was calculated 40.729 mg/g. LD50 value by brine shrimp test was 0.158 mg/ml. The extract decreased number of VEBs, incidence and duration of Rev VF with clear reduction in infarct size and infarct volume (P<0.001). Conclusion: Ficus carica decreased ischemia/reperfusion-induced injuries. These protections are probably due to antioxidant capacity and the existence of flavonoid and phenolic compounds in the extract. PMID:25671192

The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people.

PubMed

Kalsi, T; Babic-Illman, G; Ross, P J; Maisey, N R; Hughes, S; Fields, P; Martin, F C; Wang, Y; Harari, D

2015-04-28

Although comorbidities are identified in routine oncology practice, intervention plans for the coexisting needs of older people receiving chemotherapy are rarely made. This study evaluates the impact of geriatrician-delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy toxicity and tolerance for older people with cancer. Comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital. The observational control group (N=70, October 2010-July 2012) received standard oncology care. The intervention group (N=65, September 2011-February 2013) underwent risk stratification using a patient-completed screening questionnaire and high-risk patients received CGA. Impact of CGA interventions on chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated. Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose reductions. Intervention participants undergoing CGA received mean of 6.2±2.6 (range 0-15) CGA intervention plans each. They were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50-11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16-0.73), P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and 52.9% in the control (P=0.292). Geriatrician-led CGA interventions were associated with improved chemotherapy tolerance. Standard oncology care should shift towards modifying coexisting conditions to optimise chemotherapy outcomes for older people.

Dandelion-enriched diet of mothers alleviates lead-induced damages in liver of newborn rats.

PubMed

Gargouri, M; Magné, C; Ben Amara, I; Ben Saad, H; El Feki, A

2017-02-28

Lead (Pb) is a highly toxic metal present in the environment. It causes disturbances of several functions, including hematologic, renal, reproductive and nervous ones. Preventive or curative use of medicinal plants against these disorders may be a promising and safe therapeutic strategy. This study evaluated the hepatic toxic effects of prenatal exposure to lead in rats and the possible protective effect of dandelion (Taraxacum officinale) added to the diet. Female rats were given a normal diet (control) or a diet enriched with dandelion (treated). In addition, lead acetate was administered to half of the rats through drinking water from the 5th day of gestation until the 14th day postpartum. Lead toxicity was evaluated in their offspring by measuring body and liver weights, plasma biochemical parameters, liver damage, as well as protein content and activities of antioxidant enzymes in the liver tissues. Lead poisoning of mothers caused lead deposition in blood and stomach of their pups as well as hepatic tissue damages. Moreover, significant decreases in liver weight and protein content were found. Lead treatment caused oxidative stress and marked changes in the activity of antioxidant enzymes. However, no damages or biochemical changes were observed in puppies from the rats co-treated with lead and dandelion. These results indicate that supplementation of pregnant and lactating rats with dandelion protects their offspring against lead poisoning, likely through reduction of oxidative stress and liver damages.

Do Toxicity Identification and Evaluation Laboratory-Based Methods Reflect Causes of Field Impairment?

EPA Science Inventory

Sediment Toxicity Identification and Evaluation (TIE) methods have been developed for both interstitial waters and whole sediments. These relatively simple laboratory methods are designed to identify specific toxicants or classes of toxicants in sediments; however, the question ...

Linkage of genomic biomarkers to whole organism endpoints in a Toxicity Identification Evaluation (TIE).

EPA Science Inventory

Aquatic organisms are exposed to many toxic chemicals and interpreting the cause and effect relationships between occurrence and impairment is difficult. Toxicity Identification Evaluation (TIE) provides a systematic approach for identifying responsible toxicants. TIE relies on ...

CHARACTERIZATION AND ISOLATION OF ORGANIC TOXICANTS IN WHOLE SEDIMENT TOXICITY INDENTIFICATION EVALUATIONS (TIES)

EPA Science Inventory

Development of whole sediment toxicity identification and evaluation (TIEs) methods has been under way for approximately four years. These methods are necessary to define cause and effect relationships in toxic sediments during ecological risk assessments, remediation and disposa...

Integration of genomic endpoints into toxicity identification evaluations

EPA Science Inventory

Toxicity identification and evaluations (TIEs) use physical/chemical manipulation of a sample to isolate or change the potency of different groups of toxicants potentially present in a sample. Organisms are then exposed to these fractions to determine if their toxicity has change...

Potential for Mercury Reduction by Microbes in the High Arctic▿

PubMed Central

Poulain, Alexandre J.; Ní Chadhain, Sinéad M.; Ariya, Parisa A.; Amyot, Marc; Garcia, Edenise; Campbell, Peter G. C.; Zylstra, Gerben J.; Barkay, Tamar

2007-01-01

The contamination of polar regions due to the global distribution of anthropogenic pollutants is of great concern because it leads to the bioaccumulation of toxic substances, methylmercury among them, in Arctic food chains. Here we present the first evidence that microbes in the high Arctic possess and express diverse merA genes, which specify the reduction of ionic mercury [Hg(II)] to the volatile elemental form [Hg(0)]. The sampled microbial biomass, collected from microbial mats in a coastal lagoon and from the surface of marine macroalgae, was comprised of bacteria that were most closely related to psychrophiles that had previously been described in polar environments. We used a kinetic redox model, taking into consideration photoredox reactions as well as mer-mediated reduction, to assess if the potential for Hg(II) reduction by Arctic microbes can affect the toxicity and environmental mobility of mercury in the high Arctic. Results suggested that mer-mediated Hg(II) reduction could account for most of the Hg(0) that is produced in high Arctic waters. At the surface, with only 5% metabolically active cells, up to 68% of the mercury pool was resolved by the model as biogenic Hg(0). At a greater depth, because of incident light attenuation, the significance of photoredox transformations declined and merA-mediated activity could account for up to 90% of Hg(0) production. These findings highlight the importance of microbial redox transformations in the biogeochemical cycling, and thus the toxicity and mobility, of mercury in polar regions. PMID:17293515

Nitrite addition to acidified sludge significantly improves digestibility, toxic metal removal, dewaterability and pathogen reduction

NASA Astrophysics Data System (ADS)

Du, Fangzhou; Keller, Jürg; Yuan, Zhiguo; Batstone, Damien J.; Freguia, Stefano; Pikaar, Ilje

2016-12-01

Sludge management is a major issue for water utilities globally. Poor digestibility and dewaterability are the main factors determining the cost for sludge management, whereas pathogen and toxic metal concentrations limit beneficial reuse. In this study, the effects of low level nitrite addition to acidified sludge to simultaneously enhance digestibility, toxic metal removal, dewaterability and pathogen reduction were investigated. Waste activated sludge (WAS) from a full-scale waste water treatment plant was treated at pH 2 with 10 mg NO2--N/L for 5 h. Biochemical methane potential tests showed an increase in the methane production of 28%, corresponding to an improvement from 247 ± 8 L CH4/kg VS to 317 ± 1 L CH4/kg VS. The enhanced removal of toxic metals further increased the methane production by another 18% to 360 ± 6 L CH4/kg VS (a total increase of 46%). The solids content of dewatered sludge increased from 14.6 ± 1.4% in the control to 18.2 ± 0.8%. A 4-log reduction for both total coliforms and E. coli was achieved. Overall, this study highlights the potential of acidification with low level nitrite addition as an effective and simple method achieving multiple improvements in terms of sludge management.

Nitrite addition to acidified sludge significantly improves digestibility, toxic metal removal, dewaterability and pathogen reduction

PubMed Central

Du, Fangzhou; Keller, Jürg; Yuan, Zhiguo; Batstone, Damien J.; Freguia, Stefano; Pikaar, Ilje

2016-01-01

Sludge management is a major issue for water utilities globally. Poor digestibility and dewaterability are the main factors determining the cost for sludge management, whereas pathogen and toxic metal concentrations limit beneficial reuse. In this study, the effects of low level nitrite addition to acidified sludge to simultaneously enhance digestibility, toxic metal removal, dewaterability and pathogen reduction were investigated. Waste activated sludge (WAS) from a full-scale waste water treatment plant was treated at pH 2 with 10 mg NO2−-N/L for 5 h. Biochemical methane potential tests showed an increase in the methane production of 28%, corresponding to an improvement from 247 ± 8 L CH4/kg VS to 317 ± 1 L CH4/kg VS. The enhanced removal of toxic metals further increased the methane production by another 18% to 360 ± 6 L CH4/kg VS (a total increase of 46%). The solids content of dewatered sludge increased from 14.6 ± 1.4% in the control to 18.2 ± 0.8%. A 4-log reduction for both total coliforms and E. coli was achieved. Overall, this study highlights the potential of acidification with low level nitrite addition as an effective and simple method achieving multiple improvements in terms of sludge management. PMID:28004811

Toxicity and genotoxicity of hospital laundry wastewaters treated with photocatalytic ozonation.

PubMed

Kern, Deivid I; Schwaickhardt, Rômulo de O; Mohr, Geane; Lobo, Eduardo A; Kist, Lourdes T; Machado, Ênio L

2013-01-15

The aim of the present study was to assess the efficiency of advanced oxidative processes based on photocatalytic ozonation (O(3), UV, UV/O(3), UV/O(3)/Fe(2+) 50 mg L(-1) and 150 mg L(-1)) in the treatment of hospital laundry wastewaters. The analysis of the investigated wastewater revealed high chemical oxygen demand (COD - 3343.8 mg L(-1)), biochemical oxygen demand (BOD(5) - 1906.4 mg L(-1)), total Kjeldahl nitrogen (TKN - 79.8 mg L(-1)) and Daphnia magna toxicity (EC50=1.73). Genotoxic effects were also detected for Allium cepa. Reductions of some parameters occurred after photocatalytic ozonation. The UV/O(3)/Fe(2+) 150 mg L(-1) method was more efficient in reducing COD (59.1%), BOD(5) (50.3%) and TKN (86.8%). There was significant reduction (p<0.05) in D. magna toxicity, O(3) (EC50=47.3%), UV (EC50=50.6%) and UV/O(3)/Fe(2+) 150 mg L(-1) (EC50=45.4%) processes. Normalization of the mitotic index and reduction of micronucleated cells were observed in A. cepa after the treatments. Results demonstrate that these methods were efficient in the degradation of hospital laundry wastewaters, representing a thriving alternative for the removal of pollutants that cause toxicity and genotoxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Magnitudes of biomarker reductions in response to controlled reductions in cigarettes smoked per day: a one-week clinical confinement study.

PubMed

Theophilus, Eugenia H; Coggins, Christopher R E; Chen, Peter; Schmidt, Eckhardt; Borgerding, Michael F

2015-03-01

Tobacco toxicant-related exposure reduction is an important tool in harm reduction. Cigarette per day reduction (CPDR) occurs as smokers migrate from smoking cigarettes to using alternative tobacco/nicotine products, or quit smoking. Few reports characterize the dose-response relationships between CPDR and effects on exposure biomarkers, especially at the low end of CPD exposure (e.g., 5 CPD). We present data on CPDR by characterizing magnitudes of biomarker reductions. We present data from a well-controlled, one-week clinical confinement study in healthy smokers who were switched from smoking 19-25 CPD to smoking 20, 10, 5 or 0 CPD. Biomarkers were measured in blood, plasma, urine, and breath, and included smoke-related toxicants, urine mutagenicity, smoked cigarette filter analyses (mouth level exposure), and vital signs. Many of the biomarkers (e.g., plasma nicotine) showed strong CPDR dose-response reductions, while others (e.g., plasma thiocyanate) showed weaker dose-response reductions. Factors that lead to lower biomarker reductions include non-CPD related contributors to the measured response (e.g., other exposure sources from environment, life style, occupation; inter-individual variability). This study confirms CPDR dose-responsive biomarkers and suggests that a one-week design is appropriate for characterizing exposure reductions when smokers switch from cigarettes to new tobacco products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

PubMed Central

Zarabla, Alessia; Ungania, Sara; Cacciatore, Alessandra; Maialetti, Andrea; Petreri, Gianluca; Mengarelli, Andrea; Spadea, Antonio; Marchesi, Francesco; Renzi, Daniela; Gumenyuk, Svitlana; Strigari, Lidia; Maschio, Marta

2017-01-01

Summary Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the frontoparietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

Effects of short-chain chlorinated paraffins exposure on the viability and metabolism of human hepatoma HepG2 cells.

PubMed

Geng, Ningbo; Zhang, Haijun; Zhang, Baoqin; Wu, Ping; Wang, Feidi; Yu, Zhengkun; Chen, Jiping

2015-03-03

Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxic effects at environmentally relevant doses, limiting the evaluation of their health risks. In this study, cell viability assay and targeted metabolomic approach was used to evaluate the environmental dose (<100 μg/L) effect of SCCPs on HepG2 cells. Cell viability was found to be decreased with increases in exposure dose of SCCPs. Exposure for 48 h to C10-CPs resulted in a significant reduction in cell viability compared with 24 h, even at 1 μg/L. SCCPs exposure altered the intracellular redox status and caused significant metabolic disruptions. As a kind of peroxisome proliferator, SCCPs specifically stimulated the β-oxidation of unsaturated fatty acids and long-chain fatty acids. Meanwhile, SCCPs exposure disturbed glycolysis and amino acid metabolism, and led to the up-regulation of glutamate metabolism and urea cycle. The toxic effects of SCCPs might mainly involve the perturbation of energy production, protein biosynthesis, fatty acid metabolism, and ammonia recycling.

Development of a simple and convenient cell-based electrochemical biosensor for evaluating the individual and combined toxicity of DON, ZEN, and AFB1.

PubMed

Xia, Shuang; Zhu, Pei; Pi, Fuwei; Zhang, Yinzhi; Li, Yun; Wang, Jiasheng; Sun, Xiulan

2017-11-15

A simple and convenient cell-based electrochemical biosensor was developed to assess the individual and combined toxicity of deoxynivalenol (DON), zearalenone (ZEN), and Aflatoxin B 1 (AFB 1 ) on Hep G2 cells. The sensor was modified in succession with AuNPs (gold nanoparticles), cysteamine, and laminin. The cells interacting with laminin formed tight cell-to-electrode contacts, and collagen was used to maintain cell adhesion and viability. Electrochemical impedance spectroscopy (EIS) was developed to evaluate mycotoxin toxicity. Experimental results show that DON, ZEN, and AFB 1 caused a significant decrease in cell viability in a dose dependent manner. The EIS value decreased with concentrations of DON, ZEN, and AFB 1 in the range of 0.01-20, 0.1-50, and 0.1-3.5μg/mL, and IC 50 obtained using the developed method was 48.5, 59.0, and 3.10μg/mL, respectively. A synergistic effect was observed between DON and ZEN, an additive effect was observed between DON and AFB 1 , and an antagonism effect was found in the binary mixtures of ZEN and AFB 1 and ternary mixtures. These results were confirmed via CCK-8 assay. Utilizing SEM, we found that cells treated with mycotoxins caused significant changes in cell morphology, thus lessening cell adsorption and impedance reduction. Biological assay indicated that EIS patterns correlated with [Ca 2+ ] i concentrations and apoptosis and necrotic cells ratios, thus effecting electrochemical signals. This method is simpler, more convenient, sensitive, and has a quicker response rate than most conventional cytotoxicity evaluation methods. Copyright © 2017. Published by Elsevier B.V.

Toxicological aspects of photocatalytic degradation of selected xenobiotics with nano-sized Mn-doped TiO2.

PubMed

Ozmen, Murat; Güngördü, Abbas; Erdemoglu, Sema; Ozmen, Nesrin; Asilturk, Meltem

2015-08-01

The toxic effects of two selected xenobiotics, bisphenol A (BPA) and atrazine (ATZ), were evaluated after photocatalytic degradation using nano-sized, Mn-doped TiO2. Undoped and Mn-doped TiO2 nanoparticles were synthesized. The samples were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), UV-vis-diffuse reflectance spectra (DRS), X-ray fluorescence spectroscopy (XRF), and BET surface area. The photocatalytic efficiency of the undoped and Mn-doped TiO2 was evaluated for BPA and ATZ. The toxicity of the synthesized photocatalysts and photocatalytic by-products of BPA and ATZ was determined using frog embryos and tadpoles, zebrafish embryos, and bioluminescent bacteria. Possible toxic effects were also evaluated using selected enzyme biomarkers. The results showed that Mn-doped TiO2 nanoparticles did not cause significant lethality in Xenopus laevis embryos and tadpoles, but nonfiltered samples caused lethality in zebrafish. Furthermore, Mn-doping of TiO2 increased the photocatalytic degradation capability of nanoparticles, and it successfully degraded BPA and AZT, but degradation of AZT caused an increase of the lethal effects on both tadpoles and fish embryos. Degradation of BPA caused a significant reduction of lethal effects, especially after 2-4h of degradation. However, biochemical assays showed that both Mn-doped TiO2 and the degradation by-products caused a significant change of selected biomarkers on X. laevis tadpoles; thus, the ecological risks of Mn-doped TiO2 should be considered due to nanomaterial applications and for spilled nanoparticles in an aquatic ecosystem. Also, the risk of nanoparticles should be considered using indicator reference biochemical markers to verify the environmental health impacts. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a Minimum Performance Standard for Hand-Held Fire Extinguishers as a Replacement for Halon 1211 on Civilian Transport Category Aircraft

NASA Astrophysics Data System (ADS)

Webster, Harry

2002-08-01

One or more Halon 1211 hand-held fire extinguishers are specified in Federal Aviation Regulation (FAR) Part 25.851 as a requirement on transport category aircraft with 31 or more seats. Halon 1211 has been linked to the destruction of the ozone layer and production of new Halon 1211 has been halted per the Montreal Protocol in 1993. The phase out of Halon 1211, as the hand-held firefighting agent of choice, for civilian transport category aircraft has necessitated the development of a Minimum Performance Standard (MPS) to evaluate replacement agents. The purpose of the MPS is to insure that there is no reduction in safety, both in terms of effectiveness in fighting onboard fires and toxicity to the passengers and crew. The MPS specifies two new tests that replacement agents must pass in addition to requiring national certifications such as provided by Underwriters Laboratories. The first test evaluates the "flooding" characteristics of the agent against a hidden in-flight fire. This test determines the ability of a streaming agent to function as a flooding agent. The second test evaluates the performance of the agent in fighting a terrorist fire scenario and the associated toxicity hazard. This test measures the agent's ability to extinguish a triple-seat fire in an aircraft cabin under in-flight conditions and the toxicity characteristics of both the neat agent and the products of decomposition. This MPS will insure that the replacement agents will meet or exceed the performance of Halon 1211 both in fighting fires and maintaining a safe breathing environment in aircraft cabins.

Evaluation of anti-inflammatory potential of leaf extracts of Skimmia anquetilia

PubMed Central

Kumar, Vijender; Bhat, Zulfiqar Ali; Kumar, Dinesh; Khan, NA; Chashoo, IA

2012-01-01

Objective To evaluate anti-inflammatory potential of leaf extract of Skimmia anquetilia by in-vitro and in-vivo anti-inflammatory models. Methods Acute toxicity study was carried out to determine the toxicity level of different extract using acute toxic class method as described in Organization of Economic Co-operation and Development Guidelines No.423. Carrageenan (1% w/w) was administered and inflammation was induced in rat paw. The leaf extracts of Skimmia anquetilia were evaluated for anti-inflammatory activity by in-vitro human red blood cell (HRBC) membrane stabilization method and in-vivo carrangeenan-induced rat paw edema method. Results The in-vitro membrane stabilizing test showed petroleum ether (PE), chloroform (CE), ethyl acetate (EE), methanol (ME) and aqueous extracts (AE) showed 49.44%, 59.39%, 60.15%, 68.40% and 52.18 % protection, respectively as compared to control groups. The in-vivo results of CE, EE and ME showed 58.20%, 60.17% and 67.53% inhibition of inflammation after 6h administration of test drugs in albino rats. The potency of the leaf extracts of Skimmia anquetilia were compared with standard diclofenac (10 mg/kg) which showed 74.18% protection in in-vitro HRBC membrane stabilization test and 71.64% inhibition in in-vivo carrangeenan-induced rat paw edema model. The ME showed a dose dependent significant (P< 0.01) anti-inflammatory activity in human red blood cell membrane stabilization test and reduction of edema in carrageenan induced rat paw edema. Conclusions The present investigation has confirmed the anti-inflammatory activity of Skimmia anquetilia due to presence of bioactive phytoconstitutes for the first time and provide the pharmacological evidence in favor of traditional claim of Skimmia anquetilia as an anti- inflammatory agent. PMID:23569983

Biochar filters reduced the toxic effects of nickel on tomato (Lycopersicon esculentum L.) grown in nutrient film technique hydroponic system.

PubMed

Mosa, Ahmed; El-Banna, Mostafa F; Gao, Bin

2016-04-01

This work used the nutrient film technique to evaluate the role of biochar filtration in reducing the toxic effects of nickel (Ni(2+)) on tomato growth. Three hydroponic treatments: T1 (control), T2 (with Ni(2+)), and T3 (with Ni(2+) and biochar) were used in the experiments. Scanning electron microscopy equipped with energy dispersive X-ray spectroscopy and Fourier transform spectroscopy was used to characterize the pre- and post-treatment biochar samples. The results illustrated that precipitation, ion exchange, and complexation with surface functional groups were the potential mechanisms of Ni(2+) removal by biochar. In comparison to the control, the T2 treatment showed severe Ni-stress with alterations in cell wall structure, distortions in cell nucleus, disturbances in mitochondrial system, malformations in stomatal structure, and abnormalities in chloroplast structure. The biochar filters in T3 treatment reduced dysfunctions of cell organelles in root and shoot cells. Total chlorophyll concentration decreased by 41.6% in T2 treatment. This reduction, however, was only 20.8% due to the protective effect of the biochar filters. The presence of Ni(2+) in the systems reduced the tomato fruit yield 58.5% and 31.9% in T2 and T3, respectively. Nickel concentrations reached the toxic limit in roots, shoots, and fruits in T2, which were not observed in T3. Biochar filters in T3 also minimized the dramatic reductions in nutrients concentration in roots, shoots, and fruits, which occurred in T2 treatment due to the severe Ni-stress. Findings from this work suggested that biochar filters can be used on farms as a safeguard for wastewater irrigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Catalytic and synergistic antibacterial potential of green synthesized silver nanoparticles: Their ecotoxicological evaluation on Poecillia reticulata.

PubMed

Borase, Hemant P; Patil, Chandrashekhar D; Salunkhe, Rahul B; Suryawanshi, Rahul K; Salunke, Bipinchandra K; Patil, Satish V

2014-01-01

In the present study, stable silver nanoparticles (AgNPs) were fabricated at a rapid rate from leaf extract of medicinally important plant Alstonia macrophylla. Biosynthesized AgNPs are of spherical shape and narrow size (70 nm), exhibiting a surface plasmon resonance peak at 435 nm, and a zeta potential of -30.8 mV and have a crystalline nature. A diverse biochemical consortium of protein, terpenoids, phenolics, and flavonoids in leaf extract of A. macrophylla was found to be responsible for AgNP synthesis as evidenced from qualitative-quantitative chemical analysis and Fourier transform infrared spectroscopy studies. Nitroaromatic compounds are anthropogenic pollutants with long-lasting environmental persistence and are needed to transform into less toxic derivatives. 4-Nitrophenol and p-nitroaniline were reduced to less hazardous and commercially useful 4-aminophenol and p-phenylenediamine by phytosynthesized AgNPs. Rate constants of 0.052 and 0.040 Min(-1) were calculated for 4-nitrophenol and p-nitroaniline reduction, respectively. Thin-layer chromatography also confirms the reduction of these nitroaromatic compounds. Combinational studies could be one of the strategies to overcome microbial resistance to antibiotics. In synergistic antibacterial assay, the highest increase in a fold area of 3.84 was reported against Staphylococcus aureus using a combination of AgNPs with penicillin. Biosynthesized AgNPs were found to be less toxic (LC50 = 9.13 ppm) than chemically synthesized AgNPs having a LC50 value of 2.86 ppm against nontarget fish Poecillia reticulata. Our green nanosynthesis method offers a faster rate of formation of stable AgNPs having antibacterial and catalytic potential with lower environmental toxicity. © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Potential effect of the medicinal plants Calotropis procera, Ficus elastica and Zingiber officinale against Schistosoma mansoni in mice.

PubMed

Seif el-Din, Sayed H; El-Lakkany, Naglaa M; Mohamed, Mona A; Hamed, Manal M; Sterner, Olov; Botros, Sanaa S

2014-02-01

Calotropis procera (Ait.) R. Br. (Asclepiadaceae), Ficus elastica Roxb. (Moraceae) and Zingiber officinale Roscoe (Zingiberaceae) have been traditionally used to treat many diseases. The antischistosomal activity of these plant extracts was evaluated against Schistosoma mansoni. Male mice exposed to 80 ± 10 cercariae per mouse were divided into two batches. The first was divided into five groups: (I) infected untreated, while groups from (II-V) were treated orally (500 mg/kg for three consecutive days) by aqueous stem latex and flowers of C. procera, latex of F. elastica and ether extract of Z. officinale, respectively. The second batch was divided into four comparable groups (except Z. officinale-treated group) similarly treated as the first batch in addition to the antacid ranitidine (30 mg/kg) 1 h before extract administration. Safety, worm recovery, tissues egg load and oogram pattern were assessed. Calotropis procera latex and flower extracts are toxic (50-70% mortality) even in a small dose (250 mg/kg) before washing off their toxic rubber. Zingiber officinale extract insignificantly decrease (7.26%) S. mansoni worms. When toxic rubber was washed off and ranitidine was used, C. procera (stem latex and flowers) and F. elastica extracts revealed significant S. mansoni worm reductions by 45.31, 53.7 and 16.71%, respectively. Moreover, C. procera extracts produced significant reductions in tissue egg load (∼34-38.5%) and positively affected oogram pattern. The present study may be useful to supplement information with regard to C. procera and F. elastica antischistosomal activity and provide a basis for further experimental trials.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

PubMed

Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase(+) was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the toxic properties of naturally weathered Exxon Valdez crude oil to surrogate wildlife species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.

1995-12-31

The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) to avian and mammalian wildlife species were evaluated using the surrogate species, mallard duck, Anas platyrhynchos, and European ferret, Mustela putorius. This study was conducted to evaluate the potential for toxic (rather than physical) injury to wildlife species that may have been exposed to WEVC, either through external contact or through dietary uptake. Previous studies have assessed the toxicity of unweathered crude oils, including Alaska North Slope Crude, but little information exists regarding the toxicity of a naturally weathered crude oil, typical of that encountered following a spill. Amore » battery of laboratory toxicity tests was conducted, in compliance with standard and published test procedures, to evaluate acute and subchronic toxicity of WEVC. These included tests of food avoidance, reproductive effects, and direct eggshell application toxicity. Naturally weathered EVC, recovered postspill from Prince William Sound, was used as the test material. 36 refs., 7 figs., 4 tabs.« less

Biotic and abiotic studies on the biological fate, transport and ecotoxicity of toxic and hazardous waste in the Mississippi River basin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdelghani, A.; Pramar, Y.; Mandal, T.

1996-05-02

This project assesses the levels of xenobiotics in Devils Swamp and studies their biological fate, transport, ecotoxicity, and potential toxicity to man. This article reports on the following studies: assessment of the acute toxicity of individual xenobiotics and toxicity of organic compounds hexachlorobutadience (HCB) and hexachlorobenzene (HCBD) on juvenile crayfish; determination of the biotic influence of temperature, salinity, pH, oxidation-reduction potential, and sediment composition on the migration of xenobiotics; development of a pharmacokinetics model for xenobiotic absorption and storage, distribution and excretion by fish and crayfish.

Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.

PubMed

Zhang, Rong; Saito, Ryuta; Mano, Yui; Kanamori, Masayuki; Sonoda, Yukihiko; Kumabe, Toshihiro; Tominaga, Teiji

2014-01-30

Convection-enhanced delivery (CED) has been developed as a potentially effective drug-delivery strategy into the central nervous system. In contrast to systemic intravenous administration, local delivery achieves high concentration and prolonged retention in the local tissue, with increased chance of local toxicity, especially with toxic agents such as chemotherapeutic agents. Therefore, the factors that affect local toxicity should be extensively studied. With the assumption that concentration-oriented evaluation of toxicity is important for local CED, we evaluated the appearance of local toxicity among different agents after delivery with CED and studied if it is dose dependent or concentration dependent. Local toxicity profile of chemotherapeutic agents delivered via CED indicates BCNU was dose-dependent, whereas that of ACNU was concentration-dependent. On the other hand, local toxicity for doxorubicin, which is not distributed effectively by CED, was dose-dependent. Local toxicity for PLD, which is extensively distributed by CED, was concentration-dependent. Traditional evaluation of drug induced toxicity was dose-oriented. This is true for systemic intravascular delivery. However, with local CED, toxicity of several drugs exacerbated in concentration-dependent manner. From our study, local toxicity of drugs that are likely to distribute effectively tended to be concentration-dependent. Concentration rather than dose may be more important for the toxicity of agents that are effectively distributed by CED. Concentration-oriented evaluation of toxicity is more important for CED. Copyright © 2013 Elsevier B.V. All rights reserved.

TIE METHODS FOR TOXICITY EVALUATION OF FRESHWATER SEDIMENTS

EPA Science Inventory

Three toxicity identification evaluation (TIE) methods, AVS spiking, zero-valent metal and cation exchange resin, have been used with metal contaminated and enriched sediments to remove the toxicity...

[Current situation of toxicity classification of Chinese materia medica and its research thoughts].

PubMed

Sun, Wenyan; Hou, Xiujuan; Wang, Bin; Zhu, Yuelan; Zhang, Shuofeng; Chang, Hongsheng; Sun, Jianning

2012-08-01

Toxicity of Chinese materia medica (CMM) is an important part of Chinese herbal nature theory. In clinical application, the dosage, time limitation and compatibility of CMM is mainly determined by toxicity. At present, there is no uniform toxicity classification standard for the evaluation of Chinese herbal toxicity. Therefore, it is significant to research toxicity classification of CMM. The current situation of toxicity classification of CMM is reviewed in this paper, and proposed research thoughts are as follows: the measurement of toxicity parameters, the confirmation of poisoning target organs, the investigation on toxic mechanism by serum pharmacology and toxicokinetics, the comprehensive evaluation on toxicity based on quantitative theory.

Establishment of a bioassay for the toxicity evaluation and quality control of Aconitum herbs.

PubMed

Qin, Yi; Wang, Jia-bo; Zhao, Yan-ling; Shan, Li-mei; Li, Bao-cai; Fang, Fang; Jin, Cheng; Xiao, Xiao-he

2012-01-15

Currently, no bioassay is available for evaluating the toxicity of Aconitum herbs, which are well known for their lethal cardiotoxicity and neurotoxicity. In this study, we established a bioassay to evaluate the toxicity of Aconitum herbs. Test sample and standard solutions were administered to rats by intravenous infusion to determine their minimum lethal doses (MLD). Toxic potency was calculated by comparing the MLD. The experimental conditions of the method were optimized and standardized to ensure the precision and reliability of the bioassay. The application of the standardized bioassay was then tested by analyzing 18 samples of Aconitum herbs. Additionally, three major toxic alkaloids (aconitine, mesaconitine, and hypaconitine) in Aconitum herbs were analyzed using a liquid chromatographic method, which is the current method of choice for evaluating the toxicity of Aconitum herbs. We found that for all Aconitum herbs, the total toxicity of the extract was greater than the toxicity of the three alkaloids. Therefore, these three alkaloids failed to account for the total toxicity of Aconitum herbs. Compared with individual chemical analysis methods, the chief advantage of the bioassay is that it characterizes the total toxicity of Aconitum herbs. An incorrect toxicity evaluation caused by quantitative analysis of the three alkaloids might be effectively avoided by performing this bioassay. This study revealed that the bioassay is a powerful method for the safety assessment of Aconitum herbs. Copyright © 2011 Elsevier B.V. All rights reserved.

An evaluation of inorganic toxicity reference values for use in assessing hazards to American robins (Turdus migratorius)

USGS Publications Warehouse

Beyer, W. Nelson; Sample, Bradley E.

2017-01-01

When performing screening-level and baseline risk assessments, assessors usually compare estimated exposures of wildlife receptor species with toxicity reference values (TRVs). We modeled the exposure of American robins (Turdus migratorius) to 10 elements (As, Cd, Cr, Cu, Hg, Mn, Pb, Se, Zn, and V) in spring and early summer, a time when earthworms are the preferred prey. We calculated soil benchmarks associated with possible toxic effects to these robins from 6 sets of published TRVs. Several of the resulting soil screening-level benchmarks were inconsistent with each other and less than soil background concentrations. Accordingly, we examined the derivations of the TRVs as a possible source of error. In the case of V, a particularly toxic chemical compound (ammonium vanadate) containing V, not normally present in soil, had been used to estimate a TRV. In the cases of Zn and Cu, use of uncertainty values of 10 in estimating TRVs led to implausibly low soil screening values. In the case of Pb, a TRV was calculated from studies demonstrating reductions in egg production in Japanese quail (Coturnix coturnix japonica) exposed to Pb concentrations well below than those causing toxic effects in other species of birds. The results on quail, which were replicated in additional trials, are probably not applicable to other, unrelated species, although we acknowledge that only a small fraction of all species of birds has been tested. These examples underscore the importance of understanding the derivation and relevance of TRVs before selecting them for use in screening or in ecological risk assessment.

Reduction of the Algicidal Properties of Copper and Mercury Ions by Chitin and Chitosan.

ERIC Educational Resources Information Center

Blair, Hal S.; And Others

1982-01-01

When chitin and chitosan were added to growing cultures of Chlorella containing various quantities of toxic metals (copper and mercury), it was found that the presence of these materials reduced the toxic effect of the metals. Background information, procedures, and results are provided for this experiment. (Author/JN)

Reduction of Fumonisin Toxicity by Extrusion and Nixtamalization (Alkaline Cooking)

USDA-ARS?s Scientific Manuscript database

Fumonisins are found in corn. The most common, fumonisin FB1 (FB1) is toxic to animals, disrupts sphingolipid metabolism, and is a suspected risk factor for neural tube defects (NTDs; serious birth defect) and cancer in humans that consume contaminated corn as a diet staple. FB1 levels in foods an...

Effect of ultrasonic and ozone pre-treatments on pharmaceutical waste activated sludge's solubilisation, reduction, anaerobic biodegradability and acute biological toxicity.

PubMed

Pei, Jin; Yao, Hong; Wang, Hui; Shan, Dan; Jiang, Yichen; Ma, Lanqianya; Yu, Xiaohua

2015-09-01

Ultrasonic and ozone pre-treatment technologies were employed in this study to improve the anaerobic digestion efficiency of pharmaceutical waste activated sludge. The sludge solubilisation achieved 30.01% (150,000 kJ/kg TS) and 28.10% (0.1g O3/g TS) after ultrasonic treatment and ozone treatment. The anaerobic biodegradability after ultrasonic treatment was higher compared to ozonation due to the higher cumulative methane volume observed after 6 days (249 ml vs 190 ml). The ozonated sludge released the highest concentration of Cu(2+) into the liquid phase (6.640 mg L(-1)) compared to 0.530 mg/L for untreated sludge and 0.991 mg/L for sonicated sludge. The acute toxicity test measured by luminescent bacteria showed that anaerobic digestion could degrade toxic compounds and result in a reduction in toxicity. The main mechanism of action led to some differences in the treated sludge exhibiting higher potential for methane production from pharmaceutical waste sludge with ultrasonic treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduction of hexavalent chromium by the thermophilic methanogen Methanothermobacter thermautotrophicus

DOE PAGES

Singh, Rajesh; Dong, Hailiang; Liu, Deng; ...

2014-10-22

Despite the significant progress on iron reduction by thermophilic microorganisms, studies on their ability to reduce toxic metals are still limited, despite their common co-existence in high temperature environments (up to 70°C). In this study, Methanothermobacter thermautotrophicus, an obligate thermophilic methanogen, was used to reduce hexavalent chromium. Experiments were conducted in a growth medium with H 2/CO 2 as substrate with various Cr 6+ concentrations (0.2, 0.4, 1, 3, and 5 mM) in the form of potassium dichromate (K 2Cr 2O 7). Time-course measurements of aqueous Cr 6+ concentrations with the 1, 5-diphenylcarbazide colorimetric method showed complete reduction of themore » 0.2 and 0.4 mM Cr 6+ solutions by this methanogen. However, much lower reduction extents of 43.6%, 13.0%, and 3.7% were observed at higher Cr 6+ concentrations of 1, 3 and 5 mM, respectively. These lower extents of bioreduction suggest a toxic effect of aqueous Cr 6+ to cells at this concentration range. At these higher Cr 6+ concentrations, methanogenesis was inhibited and cell growth was impaired as evidenced by decreased total cellular protein production and live/dead cell ratio. Likewise, Cr 6+ bioreduction rates decreased with increased initial concentrations of Cr 6+ from 13.3 to1.9 μM h ₋1. X-ray absorption near-edge structure (XANES) spectroscopy revealed a progressive reduction of soluble Cr 6+ to insoluble Cr 3+ precipitates, which was confirmed as amorphous chromium hydroxide by X-ray diffraction and selected area electron diffraction pattern. However, a small fraction of reduced Cr occurred as aqueous Cr 3+. Scanning and transmission electron microscope observations of M. thermautotrophicus cells after Cr 6+ exposure suggest both extra- and intracellular chromium reduction mechanisms. Results of this study demonstrate the ability of M. thermautotrophicus cells to reduce toxic Cr 6+ to less toxic Cr 3+ and its potential application in metal bioremediation, especially at high temperature subsurface radioactive waste disposal sites, where the temperature may reach ~70°C.« less

Adolescent smokers' response to reducing the nicotine content of cigarettes: Acute effects on withdrawal symptoms and subjective evaluations.

PubMed

Cassidy, Rachel N; Colby, Suzanne M; Tidey, Jennifer W; Jackson, Kristina M; Cioe, Patricia A; Krishnan-Sarin, Suchitra; Hatsukami, Dorothy

2018-05-15

Mandating a reduction in the nicotine content of cigarettes to a minimally addictive level could dramatically reduce smoking rates in the US. However, little is known about the effects of reduced nicotine content cigarettes in adolescents. Following overnight abstinence, adolescent daily smokers (ages 15-19, n = 50) reported on their craving, withdrawal, and positive and negative affect pre- and post- ad lib smoking of one cigarette containing varying nicotine content (15.8, 5.2, 1.3 and 0.4 mg/g of tobacco) in the laboratory and reported their subjective evaluations of each cigarette. Carbon monoxide (CO) boost from pre- to post-cigarette was calculated to determine if lower-nicotine cigarettes led to differential acute changes in toxicant exposure. All four nicotine cigarette types significantly reduced abstinence-induced craving, withdrawal, and negative affect (all p's < .05). Mixed models evaluating the effect of nicotine content, with nicotine dependence level and gender included as covariates, revealed a significant effect of nicotine content on craving and subjective evaluations: higher nicotine content resulted in greater reductions in craving and increases in both positive and negative subjective evaluations. There were no significant effects of nicotine dose on withdrawal symptoms, negative affect, or CO boost. These results suggest that lower nicotine cigarettes might result in reduced abuse liability compared to higher nicotine content cigarettes due to reduced positive subjective effects, while still reducing withdrawal, in adolescents. These results highlight the potential feasibility of this policy approach and support continued research on how a nicotine reduction policy may affect adolescent smoking patterns. Copyright © 2018 Elsevier B.V. All rights reserved.

EVALUATION OF ALTERNATIVE REFERENCE TOXICANTS FOR USE IN THE EARTHWORM TOXICITY TEST

EPA Science Inventory

The use of the 14-d earthworm toxicity test to aid in the evaluation of the ecological impact of contaminated soils is becoming increasingly widespread. However,the method is in need of further standardization. As part of this continuing process, the choice of reference toxicants...

WHAT’S CAUSING TOXICITY IN SEDIMENTS? RESULTS OF 20 YEARS OF TOXICITY IDENTIFICATION AND EVALUATIONS

EPA Science Inventory

Sediment toxicity identification and evaluation (TIE) methods have been used for 20 yr to identify the causes of toxicity in sediments around the world. In the present study, the authors summarize and categorize results of 36 peer-reviewed TIE studies (67 sediments) into nonioni...

What’s Causing Toxicity in Sediments? Results of Twenty Years of Toxicity Identification and Evaluations (TIEs)

EPA Science Inventory

Sediment Toxicity Identification and Evaluation (TIEs) methods have been used for twenty years to identify the causes of toxicity in sediments around the world. We summarized and categorized results of more than 80 peer-reviewed TIE studies into non-ionic organic, cationic, ammo...

Inhibitory Effects of Sulfate and Nitrate Reduction on Reductive Dechlorination of PCP in a Flooded Paddy Soil

PubMed Central

Xu, Yan; Xue, Lili; Ye, Qi; Franks, Ashley E.; Zhu, Min; Feng, Xi; Xu, Jianming; He, Yan

2018-01-01

Pentachlorophenol (PCP) is highly toxic and persistent in soils. Bioreduction of PCP often co-occurs with varying concentrations of sulfate and nitrate in flooded paddy soils where each can act as an electron acceptor. Anaerobic soil microcosms were constructed to evaluate the influence of sulfate and nitrate amendments and their redox processes. Microcosms with varying sulfate and nitrate concentrations demonstrated an inhibitory effect on reductive dechlorination of PCP compared to an untreated control. Compared to nitrate, sulfate exhibited a more significant impact on PCP dechlorination, as evidenced by a lower maximum reaction rate and a longer time to reach the maximum reaction rate. Dechlorination of PCP was initiated at the ortho-position, and then at the para- and meta-positions to form 3-CP as the final product in all microcosms. Deep sequencing of microbial communities in the microcosms revealed a strong variation in bacterial taxon among treatments. Specialized microbial groups, such as the genus of Desulfovibrio responding to the addition of sulfate, had a potential to mediate the competitive microbial dechlorination of PCP. Our results provide an insight into the competitive microbial-mediated reductive dechlorination of PCP in natural flooded soil or sediment environments. PMID:29643842

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity.

PubMed

Leite, Elaine A; Souza, Cristina M; Carvalho-Júnior, Alvaro D; Coelho, Luiz G V; Lana, Angela M Q; Cassali, Geovanni D; Oliveira, Mônica C

2012-01-01

Cisplatin (CDDP) is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study's research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non- pH-sensitive liposomes containing CDDP (NSpHL-CDDP), after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF) levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was observed after SpHL-CDDP treatment, compared with free CDDP and NSpHL-CDDP treatments. In addition, complete remission of the tumor was detected in 18.2% of the mice treated with SpHL- CDDP (16 mg/kg). As such, the administration of SpHL-CDDP, as compared with free CDDP and NSpHL-CDDP, led to a decrease in the area of necrosis and in the percentage of positive CDC 47 tumor cells. A significant reduction in the VEGF serum level was also observed after SpHL-CDDP treatment, as compared with free-CDDP treatment. SpHL-CDDP administered in a two-fold higher dose than that of free CDDP presented a loss in body weight and changes in the hematopoietic tissue morphology, which proved to be similar to that of free CDDP. No changes could be verified in the renal tissue after any formulations containing CDDP had been administered. These findings showed that SpHL-CDDP allowed for the administration of higher doses of CDDP, significantly improving its antitumor effect.

Effects of aqueous uranyl speciation on the kinetics of microbial uranium reduction

DOE PAGES

Belli, Keaton M.; DiChristina, Thomas J.; Van Cappellen, Philippe; ...

2015-02-16

The ability to predict the success of the microbial reduction of soluble U(VI) to highly insoluble U(IV) as an in situ bioremediation strategy is complicated by the wide range of geochemical conditions at contaminated sites and the strong influence of aqueous uranyl speciation on the bioavailability and toxicity of U(VI) to metal-reducing bacteria. In order to determine the effects of aqueous uranyl speciation on uranium bioreduction kinetics, incubations and viability assays with Shewanella putrefaciens strain 200 were conducted over a range of pH and dissolved inorganic carbon (DIC), Ca 2+, and Mg 2+ concentrations. A speciation-dependent kinetic model was developedmore » to reproduce the observed time series of total dissolved uranium concentration over the range of geochemical conditions tested. The kinetic model yielded the highest rate constant for the reduction of uranyl non-carbonate species (i.e., the ‘free’ hydrated uranyl ion, uranyl hydroxides, and other minor uranyl complexes), indicating that they represent the most readily reducible fraction of U(VI) despite being the least abundant uranyl species in solution. In the presence of DIC, Ca 2+, and Mg 2+ is suppressed during the formation of more bioavailable uranyl non-carbonate species and resulted in slower bioreduction rates. At high concentrations of bioavailable U(VI), however, uranium toxicity to S. putrefaciens inhibited bioreduction, and viability assays confirmed that the concentration of non-carbonate uranyl species best predicts the degree of toxicity. The effect of uranium toxicity was accounted for by incorporating the free ion activity model of metal toxicity into the bioreduction rate law. These results demonstrate that, in the absence of competing terminal electron acceptors, uranium bioreduction kinetics can be predicted over a wide range of geochemical conditions based on the bioavailability and toxicity imparted on U(VI) by solution composition. Finally, these findings also imply that the concentration of uranyl non-carbonate species, despite being extremely low, is a determining factor controlling uranium bioreduction at contaminated sites.« less

Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM)more » and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60 cells under granulocytic differentiation were vulnerable for clozapine. • HL-60 cells would be in vitro assay systems for hematopoietic toxicity by clozapine. • Histamine H{sub 4} receptor was involved in hematopoietic toxicity with apoptosis. • Histamine H{sub 4} receptor may be therapeutic target to prevent hematopoietic toxicity.« less

Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants

DTIC Science & Technology

1997-08-01

AL/EQ-TR-1997-0050 DEVELOPMENT AND EVALUATION OF REPRODUCTIVE AND DEVELOPMENT TOXICITY TESTS FOR ASSESSING THE HAZARDS OF ENVIRONMENTAL...SUBTITLE Development and Evaluation of Reproductive and Developmental Toxicity Tests for Assessing the Hazards of Environmental Contaminants 6...pd in testing toxicity in surface waters, ground waters and H- ™t™j£J^^^M hazard assessment when used in conjunction in sediments. FETAX can be usea

Effect of culture age on 1,3-dinitrobenzene metabolism and indicators of cellular toxicity in rat testicular cells.

PubMed

Brown, C D; Miller, M G

1991-01-01

The metabolism and toxicity of 1,3-dinitrobenzene(1,3-DNB) were examined in rat testicular cells that had been cultured for various amounts of time. The three cell systems utilized were: freshly isolated suspensions of Sertoli/germ cells; the same Sertoli/germ cells co-cultured for 24 hr; and Sertoli cell-enriched monolayers derived from the co-cultures and cultured for 96 hr. Indicators of toxicity were MTT reduction, neutral red incorporation, cellular ATP levels and lactate secretion into the media. 1,3-DNB (5-50 mum) caused a significant concentration-dependent decline in cellular ATP levels in the fresh cell suspension, but not in the cells that had been cultured for longer. No changes were observed either in MTT reduction or neutral red incorporation. Increased secretion of lactate into the media also did not prove to be a sensitive indicator of toxicity. Interestingly, 1,3-DNB metabolism to nitroaniline, nitroacetanilide and a covalently bound species was two to three times greater in the fresh cells, compared with either the 24- or 96-hr cell cultures. The data indicate that time in culture may have significant effects on both the capacity of testicular cells to metabolize 1,3-DNB and susceptibility to toxicity.

The sequential use of washing and an electrochemical reduction process for the remediation of lead-contaminated soils.

PubMed

Demir, Aydeniz; Köleli, Nurcan

2013-01-01

A two-step method for the remediation of three different types of lead (Pb)-contaminated soil was evaluated. The first step included soil washing with ethylenediaminetetraacetic acid (EDTA) to remove Pb from soils. The washing experiments were performed with 0.05 M Na2EDTA at 1:10 soil to liquid ratio. Following the washing, Pb removal efficiency from soils ranged within 50-70%. After the soil washing process, Pb2+ ions in the washing solution were reduced electrochemically in a fixed-bed reactor. Lead removal efficiency with the electrochemical reduction at -2.0 V potential ranged within 57-76%. The overall results indicate that this two-step method is an environmentally-friendly and effective technology to remediate Pb-contaminated soils, as well as Pb-contaminated wastewater treatment due to the transformation of toxic Pb2+ ions into a non-hazardous metallic form (Pb(0)).

Evaluation of the Polyethylene Reverse Sampler as a Dosing System in Marine Phase II Whole Sediment Toxicity Identification Evaluations (TIEs)

EPA Science Inventory

Contaminated marine sediments can cause acute and chronic impairments to benthic organisms. Nonionic organic contaminants (NOCs) are often a primary cause of impairment. Toxicity Identification Evaluations (TIEs) are used to identify chemicals causing toxicity in sediments. Ph...

Evaluation of hypoglycemic and anti-hyperglycemic potential of Tridax procumbens (Linn.).

PubMed

Pareek, Hemant; Sharma, Sameer; Khajja, Balvant S; Jain, Kusum; Jain, G C

2009-11-29

Diabetes is a metabolic disorder affecting carbohydrate, fat and protein metabolism. Tridax procumbens Linn. (Family-Asteraceae; common name-Dhaman grass) is common herb found in India. Traditionally, the tribal inhabitants of Udaipur district in Rajasthan (India) uses the leaf powder (along with other herb) orally to treat diabetes. There is a need to evaluate extracts of this plant in order to provide scientific proof for it's application in traditional medicine system. Extraction of whole plant of T. procumbens using 50%methanol. The extract was tested for acute and sub-chronic anti-hyperglycemic activity in alloxan induced diabetic rats and for acute toxicity test among normal rats. Observations on body weight as well as on the oral glucose tolerance levels were also recorded. Oral administration of acute and sub chronic doses (250 and 500 mg/kg b.wt.) of T. procumbens extract showed a significant (p < 0.05) reduction in fasting blood glucose levels in diabetic rats, however the decline in blood sugar levels in normal rats was not observed. In acute study the maximum percent blood glucose reduction (68.26% at 250 mg/kg and 71.03% at 500 mg/kg body weight) in diabetic rats was observed at 6 h. The anti-hyperglycemic effects were not dependent of dose and the OGTT and Body weight supported the antihyperglycemic action of the drug. The results of anti-diabetic effect of T. procumbens were compared with the reference standard drug Glibenclamide (10 mg/kg b.wt.). These test results support traditional medicinal use of, T. procumbens for the treatment of diabetes mellitus with corrections in body weight and oral glucose tolerance and no visible signs or symptoms of toxicity in normal rats indicating a high margin of safety. These results warrant follow-up through bioassay-directed isolation of the active principles.

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers.

PubMed

Woodford, Katrina; Panettieri, Vanessa; Ruben, Jeremy D; Senthi, Sashendra

2016-05-01

Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT). Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated. IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible. Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.

Human Collagen Injections to Reduce Rectal Dose During Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noyes, William R., E-mail: noyes@cancercenternd.com; Hosford, Charles C.; Schultz, Steven E.

Objectives: The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. Methods: This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectalmore » space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. Results: Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. Conclusions: The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities.« less

Evaluation of using aluminum sulfate and water-soluble Moringa oleifera seed lectin to reduce turbidity and toxicity of polluted stream water.

PubMed

Freitas, José Henrique Edmilson Souza; de Santana, Keissy Vanderley; do Nascimento, Ana Cláudia Claudina; de Paiva, Sérgio Carvalho; de Moura, Maiara Celine; Coelho, Luana Cassandra Breitenbach Barroso; de Oliveira, Maria Betânia Melo; Paiva, Patrícia Maria Guedes; do Nascimento, Aline Elesbão; Napoleão, Thiago Henrique

2016-11-01

Aluminum salts are used as coagulants in water treatment; however, the exposure to residual aluminum has been associated with human brain lesions. The water-soluble Moringa oleifera lectin (WSMoL), which is extracted with distilled water and isolated by chitin chromatography, has coagulant activity and is able to reduce the concentration of metal ions in aqueous solutions. This study evaluated the potential of using aluminum sulfate and WSMoL to reduce the turbidity and toxicity of water from the Cavouco stream located in Recife, Pernambuco, Brazil. The water sample used (called P1) was collected from the stream source, which was found to be strongly polluted based on physicochemical and water quality analyses, as well as ecotoxicity assays with Artemia salina and seeds of Eruca sativa and Lactuca sativa. The assays combining WSMoL and aluminum sulfate were more efficient than those that used these agents separately. Furthermore, the greatest reduction in turbidity (96.8%) was obtained with the treatment using aluminum sulfate followed by WSMoL, compared to when they were applied simultaneously (91.3%). In addition, aluminum sulfate followed by WSMoL treatment resulted in residual aluminum concentration (0.3 mg/L) that was much lower than that recorded after the treatment using only the salt (35.5 mg/L). The ecotoxicity of P1 was also strongly reduced after the treatments. In summary, the combined use of aluminum sulfate and WSMoL was efficient in promoting a strong reduction of turbidity and ecotoxicity of a polluted water sample, without resulting in a high residual aluminum concentration at the conclusion of the treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicitymore » questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.« less

A new approach for modeling patient overall radiosensitivity and predicting multiple toxicity endpoints for breast cancer patients.

PubMed

Mbah, Chamberlain; De Ruyck, Kim; De Schrijver, Silke; De Sutter, Charlotte; Schiettecatte, Kimberly; Monten, Chris; Paelinck, Leen; De Neve, Wilfried; Thierens, Hubert; West, Catharine; Amorim, Gustavo; Thas, Olivier; Veldeman, Liv

2018-05-01

Evaluation of patient characteristics inducing toxicity in breast radiotherapy, using simultaneous modeling of multiple endpoints. In 269 early-stage breast cancer patients treated with whole-breast irradiation (WBI) after breast-conserving surgery, toxicity was scored, based on five dichotomized endpoints. Five logistic regression models were fitted, one for each endpoint and the effect sizes of all variables were estimated using maximum likelihood (MLE). The MLEs are improved with James-Stein estimates (JSEs). The method combines all the MLEs, obtained for the same variable but from different endpoints. Misclassification errors were computed using MLE- and JSE-based prediction models. For associations, p-values from the sum of squares of MLEs were compared with p-values from the Standardized Total Average Toxicity (STAT) Score. With JSEs, 19 highest ranked variables were predictive of the five different endpoints. Important variables increasing radiation-induced toxicity were chemotherapy, age, SATB2 rs2881208 SNP and nodal irradiation. Treatment position (prone position) was most protective and ranked eighth. Overall, the misclassification errors were 45% and 34% for the MLE- and JSE-based models, respectively. p-Values from the sum of squares of MLEs and p-values from STAT score led to very similar conclusions, except for the variables nodal irradiation and treatment position, for which STAT p-values suggested an association with radiosensitivity, whereas p-values from the sum of squares indicated no association. Breast volume was ranked as the most significant variable in both strategies. The James-Stein estimator was used for selecting variables that are predictive for multiple toxicity endpoints. With this estimator, 19 variables were predictive for all toxicities of which four were significantly associated with overall radiosensitivity. JSEs led to almost 25% reduction in the misclassification error rate compared to conventional MLEs. Finally, patient characteristics that are associated with radiosensitivity were identified without explicitly quantifying radiosensitivity.

Ni0 encapsulated in N-doped carbon nanotubes for catalytic reduction of highly toxic hexavalent chromium

NASA Astrophysics Data System (ADS)

Yao, Yunjin; Zhang, Jie; Chen, Hao; Yu, Maojing; Gao, Mengxue; Hu, Yi; Wang, Shaobin

2018-05-01

N-doped carbon nanotubes encapsulating Ni0 nanoparticles (Ni@N-C) were fabricated via thermal reduction of dicyandiamide and NiCl2·6H2O, and used to remove CrVI in polluted water. The resultant products present an excellent catalytic activity for CrVI reduction using formic acid under relatively mild conditions. The CrVI reduction efficiency of Ni@N-C was significantly affected by the preparation conditions including the mass of nickel salt and synthesis temperatures. The impacts of several reaction parameters, such as initial concentrations of CrVI and formic acid, solution pH and temperatures, as well as inorganic anions in solution on CrVI reduction efficiency were also evaluated in view of scalable industrial applications. Owing to the synergistic effects amongst tubes-coated Ni0, doped nitrogen, oxygen containing groups, and the configuration of carbon nanotubes, Ni@N-C catalysts exhibit excellent catalytic activity and recyclable capability for CrVI reduction. Carbon shell can efficiently protect inner Ni0 core and N species from corrosion and subsequent leaching, while Ni0 endows the Ni@N-C catalysts with ferromagnetism, so that the composites can be easily separated via a permanent magnet. This study opens up an avenue for design of N-doped carbon nanotubes encapsulating Ni0 nanoparticles with high CrVI removal efficiency and magnetic recyclability as low-cost catalysts for industrial applications.

Bioprocess development for hexavalent chromium reduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turick, C.E.; Apel, W.A.

1996-10-01

Hexavalent chromium (Cr(VI)) exists in the environment from anthropogenic activity and is regarded as a highly mobile and toxic pollutant. There is considerable interest in developing effective and efficient methods for the remediation of contaminated media. Many bacterial isolates have been demonstrated to metabolically reduce Cr(VI) to Cr(III), a much less toxic, more easily recoverable form of chromium. Aerobic and anaerobic cultures of Cr(VI) reducing bacteria were analyzed for their ability to reduce Cr(VI) prior to bioreactor design and scale up. Batch studies demonstrated Cr(VI) reduction rates with aerobic bacteria of up to 3 mg/hr/g dry cells, while anaerobic culturesmore » exhibited Cr(VI) reduction rates up to 22 mg/hr/g dry cells. An aerobic mixed culture of Cr(VI) reducing bacteria was chosen for bioreactor studies due to better rates of Cr(VI) reduction as well as the robust nature of the culture. These properties will allow for ease in bioprocess operation in the field.« less

Evaluation of attractive toxic sugar bait (ATSB)—barrier for control of vector and nuisance mosquitoes and its effect on non-target organisms in sub-tropical environments in Florida

PubMed Central

Qualls, Whitney A.; Müller, Günter C.; Revay, Edita E.; Allan, Sandra A.; Arheart, Kristopher L.; Beier, John C.; Smith, Michal L.; Scott, Jodi M.; Kravchenko, Vasiliy D.; Hausmann, Axel; Yefremova, Zoya A.; Xue, Rui-De

2014-01-01

The efficacy of attractive toxic sugar baits (ATSB) with the active ingredient eugenol, an Environmental Protection Agency exempt compound, was evaluated against vector and nuisance mosquitoes in both laboratory and field studies. In the laboratory, eugenol combined in attractive sugar bait (ASB) solution provided high levels of mortality for Aedes aegypti, Culex quinquefasciatus, and Anopheles quadrimaculatus. Field studies demonstrated significant control: > 70% reduction for Aedes atlanticus, Ae. infirmatus, and Culex nigripalpus and > 50% reduction for An. crucians, Uranotaenia sapphirina, Culiseta melanura, and Cx. erraticus three weeks post ATSB application. Furthermore, non-target feeding of six insect orders, Hymenoptera, Lepidoptera, Coleoptera, Diptera, Hemiptera, and Orthoptera, was evaluated in the field after application of a dyed-ASB to flowering and non-flowering vegetation. ASB feeding (staining) was determined by dissecting the guts and searching for food dye with a dissecting microscope. The potential impact of ATSB on non-targets, applied on green non-flowering vegetation was low for all non-target groups (0.9%). However, application of the ASB to flowering vegetation resulted in significant staining of the non-target insect orders. This highlights the need for application guidelines to reduce non-target effects. No mortality was observed in laboratory studies with predatory non-targets, spiders, praying mantis, or ground beetles, after feeding for three days on mosquitoes engorged on ATSB. Overall, our laboratory and field studies support the use of eugenol as an active ingredient for controlling important vector and nuisance mosquitoes when used as an ATSB toxin. This is the first study demonstrating effective control of anophelines in non-arid environments which suggest that even in highly competitive sugar rich environments this method could be used for control of malaria in Latin American countries. PMID:24361724

Protective effects of the dietary supplementation of turmeric (Curcuma longa L.) on sodium arsenite-induced biochemical perturbation in mice.

PubMed

Karim, Md Rezaul; Haque, Abedul; Islam, Khairul; Ali, Nurshad; Salam, Kazi Abdus; Saud, Zahangir Alam; Hossain, Ekhtear; Fajol, Abul; Akhand, Anwarul Azim; Himeno, Seiichiro; Hossain, Khaled

2010-12-01

The present study was undertaken to evaluate the protective effect of turmeric powder on arsenic toxicity through mice model. Swiss albino male mice were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were treated with turmeric powder (T, 50 mg/kg body weight/day), sodium arsenite (Sa, 10 mg/kg body weight/day) and turmeric plus Sa (T+Sa), respectively. Results showed that oral administration of Sa reduced the weight gain of the mice compared to the control group and food supplementation of turmeric prevented the reduction of weight gain. Turmeric abrogated the Sa-induced elevation of serum urea, glucose, triglyceride (TG) level and alanine aminotransferase (ALT) activity except the activity of alkaline phosphatase (ALP). Turmeric also prevented the Sa-induced perturbation of serum butyryl cholinesterase activity (BChE). Therefore, ameliorating effect of turmeric on Sa-treated mice suggested the future application of turmeric to reduce or to prevent arsenic toxicity in human.

Tecoma sambucifolia: anti-inflammatory and antinociceptive activities, and 'in vitro' toxicity of extracts of the 'huarumo' of peruvian incas.

PubMed

Alguacil, L F; Galán de Mera, A; Gómez, J; Llinares, F; Morales, L; Muñoz-Mingarro, M D; Pozuelo, J M; Vicente Orellana, J A

2000-06-01

Aqueous and alcoholic extracts of pods and flowers of Tecoma sambucifolia H.B.K. (Bignoniaceae) ('huarumo') were analysed to determine their anti-inflammatory activity (carrageenan-induced edema test), antinociceptive activity (acetic acid writhing test) and 'in vitro' toxicity in Chinese hamster ovary cells, human hepatome cells and human larynx epidermal carcinoma cells. The cytotoxic effects of both extracts were evaluated by two endpoint systems: neutral red uptake assay and tetrazolium assay. The results showed that all extracts have anti-inflammatory and antinociceptive activity, but the highest potency is that of the alcoholic extracts. There were significant differences in cytotoxicity between extracts and among the response of cells to them. The highest cytotoxicity was noted with the alcoholic extract, and the human hepatome cell line was the most sensitive, especially to the alcoholic extract of flowers. The aqueous pod extract appeared to have the best pharmaco-toxicological profile, since it provided a significant reduction of both pain and inflammation together with the lowest cytotoxicity.

CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

PubMed Central

Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

2017-01-01

The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500–2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2. PMID:28054631

Asialoglycoprotein receptor targeted delivery of doxorubicin nanoparticles for hepatocellular carcinoma.

PubMed

Pranatharthiharan, Sandhya; Patel, Mitesh D; Malshe, Vinod C; Pujari, Vaishali; Gorakshakar, Ajit; Madkaikar, Manisha; Ghosh, Kanjaksha; Devarajan, Padma V

2017-11-01

We report asialoglycoprotein receptor (ASGPR)-targeted doxorubicin hydrochloride (Dox) nanoparticles (NPs) for hepatocellular carcinoma (HCC). Polyethylene sebacate (PES)-Gantrez® AN 119 Dox NPs of average size 220 nm with PDI < 0.62 and ∼20% Dox loading were prepared by modified nanoprecipitation. ASGPR ligands, pullulan (Pul), arabinogalactan (AGn), and the combination (Pul-AGn), were anchored by adsorption. Ligand anchoring enabled high liver uptake with a remarkable hepatocyte:nonparenchymal cell ratio of 85:15. Furthermore, Pul-AGn NPs exhibited an additive effect implying incredibly high hepatocyte accumulation. Galactose-mediated competitive inhibition confirmed ASGPR-mediated uptake of ligand-anchored NPs in HepG2 cell lines. Subacute toxicity in rats confirmed the safety of the NP groups. However, histopathological evaluation suggested mild renal toxicity of AGn. Pul NPs revealed sustained reduction in tumor volume in PLC/PRF/5 liver tumor-bearing Nod/Scid mice up to 46 days. Extensive tumor necrosis, reduced collagen content, reduction in the HCC biomarker serum α-fetoprotein (p < 0.05), a mitotic index of 1.135 (day 46), and tumor treated/tumor control (T/C) values of <0.42 signified superior efficacy of Pul NPs. Furthermore, weight gain in the NP groups, and no histopathological alterations indicated that they were well tolerated by the mice. The high efficacy coupled with greater safety portrayed Pul Dox NPs as a promising nanocarrier for improved therapy of HCC.

CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

NASA Astrophysics Data System (ADS)

Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

2017-01-01

The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500-2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2.

Screening the Emission Sources of Volatile Organic Compounds (VOCs) in China Based on Multi-effect Evaluation

NASA Astrophysics Data System (ADS)

Niu, H., Jr.

2015-12-01

Volatile organic compounds (VOCs) in the atmosphere have adverse impacts via three main pathways: photochemical ozone formation, secondary organic aerosol production, and direct toxicity to humans. Few studies have integrated these effects to prioritize control measures for VOCs sources. In this study, we developed a multi-effect evaluation methodology based on updated emission inventories and source profiles, which was combined with ozone formation potential (OFP), secondary organic aerosol potential (SOAP), and VOC toxicity data to identify important emission sources and key species. We derived species-specific emission inventories for 152 sources. The OFPs, SOAPs, and toxicity of each source were determined, and the contribution and share of each source to each of these adverse effects was calculated. Weightings were given to the three adverse effects by expert scoring, and the integrated impact was determined. Using 2012 as the base year, solvent usage and industrial process were found to be the most important anthropogenic sources, accounting for 24.2 and 23.1% of the integrated environmental effect, respectively. This was followed by biomass burning, transportation, and fossil fuel combustion, all of which had a similar contribution ranging from 16.7 to 18.6%. The top five industrial sources, including plastic products, rubber products, chemical fiber products, the chemical industry, and oil refining, accounted for nearly 70.0% of industrial emissions. In China, emissions reductions are required for styrene, toluene, ethylene, benzene, and m/p-xylene. The 10 most abundant chemical species contributed 76.5% of the integrated impact. Beijing, Chongqing, Shanghai, Jiangsu, and Guangdong were the five leading provinces when considering the integrated effects. Besides, the chemical mass balance model (CMB) was used to verify the VOCs inventories of 47 cities in China, so as to optimize our evaluation results. We suggest that multi-effect evaluation is necessary to identify the need for abatement at the source type and substance levels.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

PubMed

Tharavichtikul, Ekkasit; Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-06-01

To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University

PubMed Central

Meungwong, Pooriwat; Chitapanarux, Taned; Chakrabandhu, Somvilai; Klunklin, Pitchayaponne; Onchan, Wimrak; Wanwilairat, Somsak; Traisathit, Patrinee; Galalae, Razvan; Chitapanarux, Imjai

2014-01-01

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale. PMID:25061573

NTCP reduction for advanced head and neck cancer patients using proton therapy for complete or sequential boost treatment versus photon therapy.

PubMed

Jakobi, Annika; Stützer, Kristin; Bandurska-Luque, Anna; Löck, Steffen; Haase, Robert; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniel; Perez, Damien; Lühr, Armin; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Perrin, Rosalind; Richter, Christian

2015-01-01

To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only. For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (∆NTCPIMXT-IMPT) as well as between IMXT and the mixed modality treatment (∆NTCPIMXT-Mix) were calculated. Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, ∆NTCPIMXT-Mix values were a factor 2-10 smaller than ∆NTCPIMXT-IMPT. Assuming a threshold of ≥ 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, ∆NTCP ≥ 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost. The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering the toxicities xerostomia and dysphagia, if a feasible strategy for patient anatomy changes is implemented.

77 FR 6801 - Agency for Toxic Substances and Disease Registry; Agency Forms Undergoing Paperwork Reduction Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... Individuals Displaced by the Hurricanes Katrina and Rita (Pilot Project)--New--Agency for Toxic Substances and... Description On August 29, 2005, Hurricane Katrina made landfall on the coast of the Gulf of Mexico near New... Hurricanes Katrina and Rita. In addition, comparisons of prevalence rates of health outcomes obtained through...

Aluminum toxicity in tomato. Part 2.Leaf gas exchange, chlorophyll content, and invertase activity

Treesearch

L. Simon; M. Kieger; Shi-Jean S. Sung; T.J. Smalley

1994-01-01

The effect of aluminum (Al) toxicity on leaf gas exchange, leaf chlorophyll content, and sucrose metabolizing enzyme activity of two tomato cultivars (Lycopersicon esculentum Mill. 'Mountain Pride' and 'Floramerica') was studied to determine the mechanism of growth reduction observed in a related study (Simon et al., 1994, Part 1).Plants were grown...

40 CFR 435.13 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2013 CFR

2013-07-01

... sediment toxicity ratio 6 shall not exceed 1.0. Biodegradation rate Biodegradation rate ratio 7 shall not...). 7 Biodegradation rate ratio = Cumulative headspace gas production (ml) of C16-C18 internal olefin... fluids that meet the base fluid sediment toxicity ratio (Footnote 6), biodegradation rate ratio (Footnote...

40 CFR 435.13 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... sediment toxicity ratio 6 shall not exceed 1.0. Biodegradation rate Biodegradation rate ratio 7 shall not...). 7 Biodegradation rate ratio = Cumulative headspace gas production (ml) of C16-C18 internal olefin... fluids that meet the base fluid sediment toxicity ratio (Footnote 6), biodegradation rate ratio (Footnote...

40 CFR 435.13 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... sediment toxicity ratio 6 shall not exceed 1.0. Biodegradation rate Biodegradation rate ratio 7 shall not...). 7 Biodegradation rate ratio = Cumulative headspace gas production (ml) of C16-C18 internal olefin... fluids that meet the base fluid sediment toxicity ratio (Footnote 6), biodegradation rate ratio (Footnote...

Permanganate with a double-edge role in photodegradation of sulfamethoxazole: Kinetic, reaction mechanism and toxicity.

PubMed

Gong, Han; Chu, Wei

2018-01-01

In this study, the double-edge role of permanganate in sulfamethoxazole (SMX) photodegradation with a recyclable catalyst was revealed for the first time. The role of the catalyst under different UV wavelength, the role of permanganate in the treatment process, the effects of permanganate dosage and solution pH on the removal efficiency were investigated. Moreover, the transformation products, TOC reduction and the toxicity of the treated final product to Chlorella vulgaris and Artemia salina were determined. Sole permanganate showed no effect in SMX degradation, while its introduction to the photocatalytic process doubled the reaction rate at the optimal dosage. It is interesting to find that the reaction rate showed a fluctuation trend in terms of permanganate dosage due to the summation of positive effect of permanganate oxidation and the negative effect of the formed MnO 2 at the surface of the catalyst, as well as the light attenuation due to overdosed permanganate. The determined intermediates, the higher inorganic ions release and TOC reduction provided a clue on a higher mineralization compared to SMX degradation in the same process without permanganate. Permanganate above 1 μM may pose a threat to the algae growth, therefore a good monitoring and control of residual permanganate dosage should be incorporated into the process design. A good toxicity reduction to A. salina was observed in the treated effluent; a longer detention is suggested for the complete removal of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

2014-01-01

Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). Conclusions. In nonhuman primates, PGJ2 administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ2 is neuroprotective when administered up to 5 hours after induction of pNAION. PMID:25298416

The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae

PubMed Central

Zhang, Weicheng; Bao, Shaopan; Fang, Tao

2016-01-01

Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te (particle) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs’ nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te (particle) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te (ion) efficiently determined the NPs toxicity associated with released ions. PMID:27094203

The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae

NASA Astrophysics Data System (ADS)

Zhang, Weicheng; Bao, Shaopan; Fang, Tao

2016-04-01

Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te (particle) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs’ nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te (particle) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te (ion) efficiently determined the NPs toxicity associated with released ions.

The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae.

PubMed

Zhang, Weicheng; Bao, Shaopan; Fang, Tao

2016-04-20

Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te ((particle)) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs' nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te ((particle)) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te ((ion)) efficiently determined the NPs toxicity associated with released ions.

Proton therapy to the subdiaphragmatic region in the management of patients with Hodgkin lymphoma.

PubMed

Sachsman, Suzanne; Hoppe, Bradford S; Mendenhall, Nancy P; Holtzman, Adam; Li, Zuofeng; Slayton, William; Joyce, Mike; Sandler, Eric; Flampouri, Stella

2015-07-01

Twelve consecutive patients with classical Hodgkin lymphoma (HL) involving diaphragmatic or subdiaphragmatic regions were treated on an institutional review board-approved outcomes tracking protocol. All patients underwent treatment with proton therapy following chemotherapy and had comparative three-dimensional conformal photon radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) plans to evaluate differences in dose to organs at risk (OARs). Among the cohort, stomach doses with 3DCRT, IMRT and proton therapy were 21 Gy (median), 14 Gy and 6 Gy, respectively. Median dose reductions with proton therapy compared with 3DCRT and IMRT were 13 Gy (p = 0.0022) and 8 Gy (p = 0.0022) for the stomach. Additionally, there was significant dose reduction using proton therapy for the liver, pancreas, bowel, left kidney and right kidney. Proton therapy reduces the dose to the stomach, liver, pancreas, small bowel and kidneys compared with 3DCRT or IMRT in patients with HL requiring abdominal radiotherapy. These dose reductions are expected to translate into lower risks of secondary cancers and other late toxicities in survivors of HL.

Electrochemical treatment of effluents containing Cr(VI). Influence of pH and current on the kinetic.

PubMed

Ruotolo, L A M; Santos-Júnior, D S; Gubulin, J C

2006-05-01

Compounds of Cr(VI) are very toxic and their reduction to Cr(III) is necessary to allow their further precipitation or adsorption. Chemical methods for Cr(VI) reduction are usually used for this purpose. As an alternative, electrochemical methods using three-dimensional electrodes, such as reticulated vitreous carbon (RVC) and polyaniline-modified RVC, have been used successfully. Since the pH affects reaction of Cr(VI) reduction, in this work its effect on the reaction rate was studied using electrodes of RVC and RVC/PANI. While a maximum in reaction rate was found for a pH 1.5 using the RVC, the RVC/PANI showed no differences in reaction rates in the range of pH between 0 and 1. Practically, no reaction was observed for any pH greater than 3. The effect of different current densities using optimized pH was also evaluated and the RVC/PANI electrode showed the best reaction rates, current efficiencies and energy consumption as a result of the polyaniline electrocatalytic effect.

Visible-light-enhanced Cr(VI) reduction at Pd-decorated silicon nanowire photocathode in photoelectrocatalytic microbial fuel cell.

PubMed

Han, He-Xing; Shi, Chen; Zhang, Nan; Yuan, Li; Sheng, Guo-Ping

2018-10-15

Hexavalent chromium (Cr(VI)) is a prominent toxic metal with significant adverse human health effects. Photocatalytic reduction of Cr(VI) to less-toxic trivalent chromium (Cr(III)) is a promising method for removing Cr(VI) from aquatic environments. However, this technique often suffers from electron-hole recombination of semiconductors and poor reduction efficiency. The photoelectrocatalytic microbial fuel cell (Photo-MFC), which can use wastewater and light to recover electricity, has recently been proven to improve the separation of photocarriers of semiconductors and enhance cathodic reduction of pollutants. Here, the reduction of Cr(VI) was investigated in a Photo-MFC with a Pd-decorated p-type silicon nanowire (Pd/SiNW) photocathode and a bioanode under visible light. The Cr(VI) reduction efficiency reached 98.7% in 8 h under visible light, which was much higher than that under dark condition (56.2%) and open-circuit condition (19.4%). The enhanced Cr(VI) removal was mainly attributed to the synergistic effect of Pd/SiNW photocathode and bioanode. Cr(VI) reduction in the Photo-MFC fitted well with pseudo-first-order kinetics. The kinetics constants and reduction efficiencies of Cr(VI) decreased with the increase of pH, initial Cr(VI) concentration and external resistance. This work provides a promising alternative to mitigate Cr(VI) pollution in aquatic environments. Copyright © 2018 Elsevier B.V. All rights reserved.

Oxidation-reduction catalyst and its process of use

NASA Technical Reports Server (NTRS)

Schryer, Jacqueline L. (Inventor); Oglesby, Donald M. (Inventor); Jordan, Jeffrey D. (Inventor); Watkins, Anthony Neal (Inventor)

2008-01-01

This invention relates generally to a ruthenium stabilized oxidation-reduction catalyst useful for oxidizing carbon monoxide, and volatile organic compounds, and reducing nitrogen oxide species in oxidizing environments, substantially without the formation of toxic and volatile ruthenium oxide species upon said oxidizing environment being at high temperatures.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). In nonhuman primates, PGJ₂ administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ₂ is neuroprotective when administered up to 5 hours after induction of pNAION. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Occupational exposure to municipal solid wastes and development of toxic neuropathies: possible role of nutrient supplementation, complementary and alternative medicines in chemoprevention.

PubMed

Ekor, Martins; Odewabi, Adesina O

2014-09-01

Achieving effective municipal solid waste (MSW) management remains a major challenge and waste generation and accumulation continue to constitute important environmental and public health concern, particularly in most developing countries. Although the general population is at risk of adverse health consequences and hazards associated with exposure to MSW, the waste management workers (WMWs) are the most vulnerable because of their direct involvement in the disposal of waste, with increasing evidence of work-related health and safety risks among these individuals. Among the numerous work-related health hazards prevalent in WMWs, development of toxic neuropathies following chronic occupational exposure remains poorly recognized. However, the risk or predisposition to toxic neuropathies is becoming evident considering the increasing recognition of large amount of neurotoxic heavy metals and hazardous industrial materials present in MSW in most parts of the world. The present review seeks to draw attention to the continuous vulnerability of the WMWs to developing toxic neuropathies. This is aimed at facilitating conscious efforts by relevant governmental and nongovernmental agencies towards promoting risk reduction and ensuring adequate protection against possible toxic polyneuropathies associated with occupational exposure to solid wastes. While continuous education of the WMWs on the need for adequate compliance to safety regulations and practice remains sacrosanct towards achieving significant reduction in toxic neuropathies and related adverse health consequences of waste handling, it is also our intention in this review to underscore the possible relevance of nutrient supplementation and alternative medicines in chemoprevention.

Reduced Uptake of FDOPA PET in End-Stage Liver Disease with Elevated Manganese Levels

PubMed Central

Criswell, Susan R; Perlmutter, Joel S; Crippin, Jeffrey S; Videen, Tom O; Moerlein, Stephen M; Flores, Hubert P; Birke, Angela M; Racette, Brad A

2013-01-01

Objective To investigate whether manganese toxicity secondary to end state liver disease is associated with nigrastriatal dysfunction as measured by 6-[18F]fluoro-L-DOPA (FDOPA) PET imaging. Design Observational case report. Setting The Movement Disorder Center at Washington University in St. Louis. Patients An individual with manganese toxicity secondary to end stage liver disease. His FDOPA PET was compared with those of 10 idiopathic Parkinson disease patients and 10 age- and sex-matched healthy controls. Main Outcome Measure The average estimated net FDOPA uptake by Patlak graphical analysis for caudate, anterior putamen and posterior putamen. Results The FDOPA uptake for the patient with secondary manganese toxicity was reduced across all regions by more than 2 SDs compared with healthy controls: caudate (reduced 24.7%), anterior putamen (28.0%), and posterior putamen (29.3%). The ratio of uptake between the caudate/posterior putamen was 0.99 and was different from that of idiopathic Parkinson disease patients, in whom the greatest reduction of FDOPA was in the posterior putamen (mean [SD] ratio, 1.65 [0.41]). Conclusions Reduce striatal uptake of FDOPA uptake indicates dysfunction of the nigrostriatal pathways in manganese toxicity secondary to end stage liver disease. The pattern of striatal involvement with equal reduction of FDOPA uptake in the caudate compared with posterior putamen appears different from those previously reported in individuals with occupational manganese toxicity and idiopathic Parkinson disease and may be specific to manganese toxicity secondary to end stage liver disease. PMID:22410448

USE OF MARINE TOXICITY IDENTIFICATION AND EVALUATION (TIE) METHODS IN DETERMINING CAUSES OF TOXICITY TO FISH IN A MARINE AQUARIUM FACILITY

EPA Science Inventory

We obtained a water sample containing broken pieces of a tropical coral reef decor that was suspected of causing fish toxicity in a major aquarium. A toxicity identification and evaluation (TIE) was performed using three species: a mysid shrimp, Americamysis bahia; inland silvers...

The effects of physicochemical properties of CeO2 nanoparticles on toxicity to soil denitrification processes

NASA Astrophysics Data System (ADS)

Dahle, Jessica Teague

The studies presented in this thesis identify the impact of NP CeO 2 on soil denitrifying microbial communities and reveal that physical and chemical characteristics including particle size, speciation, concentration, pH, and presence of ligands are key to predicting environmental fate and reactivity of NP CeO2 in the soil. A review of the literature in Chapter 1 revealed a widespread lack of toxicological information for soil exposures to NP CeO2. Soil denitrifying bacteria are a keystone species because they serve an important role in the global nitrogen cycle controlling the atmospheric nitrogen input. Soil denitrifiers are important to this study because the reducing conditions during denitrification could induce phase transformation of Ce(IV) to Ce(III), potentially influencing the toxicity of Ce. Cerium is well known for being the only lanthanide that is thermodynamically stable in both the trivalent and tetravalent state in low temperature geochemical environments. Using well characterized NP Ce(IV)O 2 as well as bulk soluble Ce(III), batch denitrification experiments were conducted to evaluate the toxicity of Ce species to the denitrifying community in a Toccoa sandy loam soil. The statistical analysis on the antimicrobial effect on soil denitrifiers was conducted using both steady-state evaluation and zero-order kinetic models in order to compare the toxicity of the Ce(III) species to the NPs. These studies, presented in Chapter 3, show that soluble Ce(III) is far more toxic than Ce(IV)O2 NPs when an equal total concentration of Ce is used, though both species exhibit toxicity to the denitrifiers via statistically significant inhibition of soil denitrification processes. Particle-size dependent toxicity, species-dependent toxicity, and concentration-dependent toxicity were all observed in this study for both the steady-state and the kinetic evaluations. The possibility of toxicity enhancement and diminishment via dissolution and ligand complexation pathways was investigated thoroughly in Chapter 2. In addition to the equilibrium and kinetic-based toxicological assessments presented in Chapter 1, dissolution and sorption experiments were performed to gain an overall understanding of Ce biogeochemistry in the terrestrial environment post-release and reveal possible geochemical controls on toxicity. It was shown that dissolution of bioavailable Ce is pH-dependent; dissolution is only detectable at acidic pH values (< pH 5) and increases with increasing acidity. Dissolution of Ce from NP CeO2 was identified to be almost 100% Ce(III). It was also demonstrated that this dissolution is suppressed by the addition of phosphate ligand, which is largely bioavailable in soils, especially in agricultural lands. This suppression was explained by the strong sorption of phosphate ligand to NP CeO2. The elimination of bioavailable Ce(III) release from NP CeO2 by phosphate ligand is likely one of the most important controls on toxicity effects and should be a large consideration in determining the fate and transport of NP CeO2 in the aquatic and terrestrial environment. It was also demonstrated that both Ce(III) and NP CeO2 have extremely strong affinity for sorption to soil matter, which could serve as another controlling pathway. Experiments indicated that factors such as reductive transformation of NP CeO2 in soils and exchangeable Ce(III) impurity in the NPs could contribute to controls on toxicity as well. In conclusion, the studies presented in this thesis indicate that the toxicity effects of the studied Ce species to soil denitrifiers are strongly affected by physical and chemical characteristics such as speciation, pH, and bioavailable ligands. As the global market for nanomaterials rapidly expands, so does the need of the scientific community for an understanding of how these influences in environmental fate and reactivity may be key in assessing toxicological risks associated with environmental exposures to NP CeO2 as well as other engineered metal oxide nanoparticles. (Abstract shortened by UMI.)

Toxicity evaluations of various carbon nanomaterials.

PubMed

Uo, Motohiro; Akasaka, Tsukasa; Watari, Fumio; Sato, Yoshinori; Tohji, Kazuyuki

2011-01-01

After the discovery of fullerene and carbon nanotubes, various carbon nanomaterials were discovered or synthesized. The carbon nanomaterials have remarkable properties, different from bulk materials with the same chemical composition, and are therefore useful for industrial applications. However, the toxicity of nanomaterials may also differ from that of the bulk materials; this difference poses a concern. The physical similarity of nanomaterials to asbestos has led to evaluations for toxicity by many researchers using various methods. In this review, we compile and compare the toxicity evaluations of each carbon nanomaterial.

Detoxification of kraft pulp ECF bleaching effluents by catalytic hydrotreatment.

PubMed

Calvo, L; Gilarranz, M A; Casas, J A; Mohedano, A F; Rodríguez, J J

2007-02-01

Two different effluents from the D(1) and E(1) stages of the ECF bleaching of Eucalyptus globulus kraft pulp were treated by catalytic hydrogenation in a trickle bed reactor using commercial and homemade Pd/AC catalysts. The reactor was fed with the bleaching effluent and a H(2)/N(2) gas stream. The variables studied were space-time (1.4-5g(cat)min/mL), gas to liquid flow ratio (286-1000vol.), gas feed concentration (H(2):N(2), 1:1-1:7.3vol.), temperature (25-100 degrees C) and pressure (1-11bar). Hydrotreatment performance was evaluated in terms of ecotoxicity, adsorbable organic halogen (AOX), chemical oxygen demand (COD), biological oxygen demand (BOD(5)) and colour removal. In all the runs, the ecotoxicity of the effluents decreased as a result of the treatment, achieving reductions that ranged from 70% to 98%. Simultaneously to the reduction of toxicity, the hydrotreatment led to a decrease of the colour of the effluents, being the decrease significantly higher in the case of E(1) effluent. The AOX content was reduced by 85% and 23% for E(1) and D(1) effluents, respectively. In the case of D(1) effluent the removal of ecotoxicity was significantly higher than that of AOX, which indicates that much of the toxicity of the effluent must be associated to non-chlorinated organics. In spite of the important reduction of ecotoxicity, the biodegradability of the effluents only increased slightly. The homemade catalysts, prepared from activated carbons with a high external or non-microporous surface area and mesopore volume and a convenient surface chemistry showed a higher efficiency than the commercial one.

Effects of particulate oxidation catalyst on unregulated pollutant emission and toxicity characteristics from heavy-duty diesel engine.

PubMed

Feng, Xiangyu; Ge, Yunshan; Ma, Chaochen; Tan, Jianwei

2015-01-01

To evaluate the effects of particulate oxidation catalyst (POC) on unregulated pollutant emission and toxicity characteristics, polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), soot, soluble organic fractions (SOF) and sulphate emissions emitted from a heavy-duty diesel engine retrofitted with a POC were investigated on a diesel bench. The particulate matter (PM) in the exhaust was collected by Teflon membrane, and the PAHs and VOCs were analysed by a gas chromatography/mass spectrometer (GC/MS). The results indicate that the POC exhibits good performance on the emission control of VOCs, PAHs and PM. The POC and the diesel particulate filters (DPF) both show a good performance on reducing the VOCs emission. Though the brake-specific emission (BSE) reductions of the total PAHs by the POC were lower than those by the DPF, the POC still removed almost more than 50% of the total PAHs emission. After the engine was retrofitted with the POC, the reductions of the PM mass, SOF and soot emissions were 45.2-89.0%, 7.8-97.7% and 41.7-93.3%, respectively. The sulphate emissions decreased at low and medium loads, whereas at high load, the results were contrary. The PAHs emissions were decreased by 32.4-69.1%, and the contributions of the PAH compounds were affected by the POC, as well as by load level. The benzo[a]pyrene equivalent (BaPeq) of PAHs emissions were reduced by 35.9-97.6% with the POC. The VOCs emissions were reduced by 21.8-94.1% with the POC, and the reduction was more evident under high load.

Evaluation of the anti-diabetic properties of Mucuna pruriens seed extract.

PubMed

Majekodunmi, Stephen O; Oyagbemi, Ademola A; Umukoro, Solomon; Odeku, Oluwatoyin A

2011-08-01

To explore the antidiabetic properties of Mucuna pruriens(M. pruriens). Diabetes was induced in Wistar rats by single intravenous injection of 120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice. Results showed that the administration of 5, 10, 20, 30, 40, 50, and 100 mg/kg of the crude ethanolic extract of M. pruriens seeds to alloxan-induced diabetic rats (plasma glucose > 450 mg/dL) resulted in 18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5 mg/kg/day) resulted in 59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity of M. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration of M. pruriens seed extract also significantly reduced the weight loss associated with diabetes. The study clearly supports the traditional use of M. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Suppression of Plutella xylostella and Trichoplusia ni in cole crops with attracticide formulations.

PubMed

Maxwell, Elly M; Fadamiro, Henry Y; McLaughlin, John R

2006-08-01

The three key lepidopteran pests of cole, Brassica oleracea L., crops in North America are diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae); cabbage looper; Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae); and imported cabbageworm, Pieris rapae (L.) (Lepidoptera: Pieridae). Two species-specific pheromone-based experimental attracticide formulations were evaluated against these pests: LastCall DBM for P. xylostella and LastCall CL for T. ni. No LastCall formulation was available against P. rapae. Laboratory toxicity experiments confirmed the effectiveness of each LastCall formulations in killing conspecific males that made contact. In replicated small plots of cabbage and collards in central Alabama, over four growing seasons (fall 2003, spring 2004, fall 2004, and spring 2005), an attracticide treatment receiving the two LastCall formulations, each applied multiple times at the rate of 1,600 droplets per acre, was compared against Bacillus thuringiensis. subspecies kursatki (Bt) spray at action threshold and a negative untreated control. Efficacy was measured by comparing among the three treatments male capture in pheromone-baited traps, larval counts in plots, and crop damage rating at harvest. LastCall provided significant reductions in crop damage comparable to Bt in three of the four seasons. Efficacy of LastCall was dependent upon lepidopteran population densities, which fluctuated from season to season. In general, reduction in crop damage was achieved with LastCall at low-to-moderate population densities of the three species, such as typically occurs in the fall in central Alabama, but not in the spring when high P. rapae population pressure typically occurs in central Alabama. Significant reductions in pheromone trap captures did not occur in LastCall plots, suggesting that elimination of males by the toxicant (permethrin), rather than interruption of sexual communication, was the main mechanism of effect.

Human microsomal cyttrochrome P450-mediated reduction of oxysophocarpine, an active and highly toxic constituent derived from Sophora flavescens species, and its intestinal absorption and metabolism in rat.

PubMed

Wu, Lili; Zhong, Wanping; Liu, Junjin; Han, Weichao; Zhong, Shilong; Wei, Qiang; Liu, Shuwen; Tang, Lan

2015-09-01

Oxysophocarpine (OSC), an active and toxic quinolizidine alkaloid, is highly valued in Sophora flavescens Ait. and Subprostrate sophora Root. OSC is used to treat inflammation and hepatitis for thousands of years in China. This study aims to investigate the CYP450-mediated reduction responsible for metabolizing OSC and to evaluate the absorption and metabolism of OSC in rat in situ. Four metabolites were identified, with sophocarpine (SC) as the major metabolite. SC formation was rapid in human and rat liver microsomes (HLMs and RLMs, respectively). The reduction rates in the liver are two fold higher than in the intestine, both in humans and rats. In HLMs, inhibitors of CYP2C9, 3A4/5, 2D6, and 2B6 had strong inhibitory effects on SC formation. Meanwhile, inhibitors of CYP3A and CYP2D6 had significant inhibition on SC formation in RLMs. Human recombinant CYP3A4/5, 2B6, 2D6, and 2C9 contributed significantly to SC production. The permeability in rat intestine and the excretion rates of metabolites were highest in the duodenum (p<0.05), and the absorbed amount of OSC in duodenum and jejunum was concentration-dependent. The metabolism could be significantly decreased by CYP3A inhibitor ketoconazole. In conclusion, the liver was the main organ responsible for OSC metabolism. First-pass metabolism via CYP3A4/5, 2B6, 2D6, and 2C9 may be the main reason for the poor OSC bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.

Thermal Stress and Toxicity | Science Inventory | US EPA

EPA Pesticide Factsheets

Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at subthermoneutral temperatures of —22 °C. When exposed to chemical toxicants under these relatively cool conditions, rodents typically undergo a regulated hypothermic response, characterized by preference for cooler ambient temperatures and controlled reduction in core temperature. Reducing core temperature delays the clearance of most toxicants from the body; however, a mild hypothermia also improves recovery and survival from the toxicant. Raising ambient temperature to thermoneutrality and above increases the rate of clearance of the toxicant but also exacerbates toxicity. Furthermore, heat stress combined with work or exercise is likely to worsen toxicity. Body temperature of large mammals, including humans, does not decrease as much in response to exposure to a toxicant. However, heat stress tan nonetheless worsen toxic outcome in humans through a variety of mechanisms. For example, heat-induced sweating and elevation in skin blood flow accelerates uptake of some insecticides. Epidemiological studies suggest that thermal stress may exacerbate the toxicity of airborne pollutants such as ozone and particulate matter. Overall, translating results of studies in rodents to that of humans is a formidable

Investigating the performance of three modified activated sludge processes treating municipal wastewater in organic pollutants removal and toxicity reduction.

PubMed

Han, Xue; Zuo, Yu-Ting; Hu, Yu; Zhang, Jie; Zhou, Meng-Xuan; Chen, Mo; Tang, Fei; Lu, Wen-Qing; Liu, Ai-Lin

2018-02-01

This study investigated the treatment performance of three types of modified activated sludge processes, i.e., anoxic/oxic (A/O), anaerobic/anoxic/oxic (A2/O) and oxidation ditch process, in treating municipal wastewater by measuring physicochemical and spectroscopic parameters, and the toxicity of the influents and effluents collected from 8 full-scale municipal wastewater treatment plants (MWTPs). The relationships between spectroscopic and physicochemical parameters of the wastewater samples and the applicability of the nematode Caenorhabditis elegans (C. elegans) bioassays for the assessment of the toxic properties of municipal wastewater were also evaluated. The results indicated that the investigated MWTPs employing any of A/O, A2/O and oxidation ditch processes could effectively control the discharge of major wastewater pollutants including biochemical oxygen demand (BOD), chemical oxygen demand, nitrogen and phosphorus. The oxidation ditch process appeared to have the advantage of removing tyrosine-like substances and presented slightly better removal efficiency of tryptophan-like fluorescent (peak T) substances than the A/O and A2/O processes. Both ultraviolet absorbance at 254nm and peak T may be used to characterize the organic load of municipal wastewater, and peak T can be adopted as a gauge of the BOD removal efficacy of municipal wastewater treatment. Using C. elegans-based oxygen consumption rate assay for monitoring municipal wastewater toxicity deserves further investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

Subsurface agricultural irrigation drainage: the need for regulation.

PubMed

Lemly, A D

1993-04-01

Subsurface drainage resulting from irrigated agriculture is a toxic threat to fish and wildlife resources throughout the western United States. Studies by the U.S. Department of the Interior show that migratory waterfowl have been poisoned by drainwater contaminants on at least six national wildlife refuges. Allowing this poisoning to continue is a violation of the Migratory Bird Treaty Act under U.S. Federal law. Critical wetlands and waterfowl populations are threatened in both the Pacific and Central flyways. The public is also at risk and health warnings have been issued in some locations. Subsurface irrigation drainage is a complex effluent containing toxic concentrations of trace elements, salts, and nitrogenous compounds. Some of the contaminants are classified by the U.S. Environmental Protection Agency (EPA) as priority pollutants and they can be present in concentrations that exceed EPA's criteria for toxic waste. The on-farm drainage systems used to collect and transport this wastewater provide point-source identification as well as a mechanism for toxics control through the National Pollutant Discharge Elimination System (NPDES) permit process. A four-step approach is presented for dealing with irrigation drainage in an environmentally sound manner. This regulatory strategy is very similar to those commonly used for industrial discharges and includes site evaluation, contaminant reduction through NPDES, and compliance monitoring. The EPA must recognize subsurface irrigation drainage as a specific class of pollution subject to regulation under the NPDES process. Active involvement by EPA is necessary to ensure that adequate controls on this wastewater are implemented.

Antimalarial activity of plumbagin in vitro and in animal models.

PubMed

Sumsakul, Wiriyaporn; Plengsuriyakarn, Tullayakorn; Chaijaroenkul, Wanna; Viyanant, Vithoon; Karbwang, Juntra; Na-Bangchang, Kesara

2014-01-12

Plumbagin is the major active constituent in several plants including Plumbago indica Linn. (root). This compound has been shown to exhibit a wide spectrum of biological and pharmacological activities. The present study aimed to evaluate the in vitro and in vivo antimalarial activity of plumbagin including its acute and subacute toxicity in mice. In vitro antimalarial activity of plumbagin against K1 and 3D7 Plasmodium falciparum clones were assessed using SYBR Green I based assay. In vivo antimalarial activity was investigated in Plasmodium berghei-infected mouse model (a 4-day suppressive test). Plumbagin exhibited promising antimalarial activity with in vitro IC50 (concentration that inhibits parasite growth to 50%) against 3D7 chloroquine-sensitive P. falciparum and K1 chloroquine-resistant P. falciparum clones of 580 (270-640) and 370 (270-490) nM, respectively. Toxicity testing indicated relatively low toxicity at the dose levels up to 100 (single oral dose) and 25 (daily doses for 14 days) mg/kg body weight for acute and subacute toxicity, respectively. Chloroquine exhibited the most potent antimalarial activity in mice infected with P. berghei ANKA strain with respect to its activity on the reduction of parasitaemia on day 4 and the prolongation of survival time. Plumbagin at the dose of 25 mg/kg body weight given for 4 days was safe and produced weak antimalarial activity. Chemical derivatization of the parent compound or preparation of modified formulation is required to improve its systemic bioavailability.

Assessment of toxicity and biodegradability on activated sludge of priority and emerging pollutants.

PubMed

Tobajas, Montserrat; Verdugo, Verónica; Polo, Alicia M; Rodriguez, Juan J; Mohedano, Angel F

2016-01-01

Several methods for evaluating the toxicity and biodegradability of hazardous pollutants (chlorinated compounds, chemical additives and pharmaceuticals) have been studied in this work. Different bioassays using representative bacteria of marine and terrestrial ecosystems such as Vibrio fischeri and Pseudomonas putida have been used to assess the ecotoxicity. Activated sludge was used to analyse the effect of those pollutants in a biological reactor of a sewage treatment plant (STP). The results demonstrate that none of the compounds is toxic to activated sludge, except ofloxacin to P. putida. The additives tested can be considered moderately toxic according to the more sensitive V. fischeri assays, whereas the EC50 values of the pharmaceuticals depend on the specific microorganism used in each test. Regarding the biodegradability, respirometric measurements were carried out for fast biodegradability assessment and the Zahn-Wellens test for inherent biodegradability. The evolution of the specific oxygen uptake rate (SOUR) showed that only diethyl phthalate was easily biodegradable and acetylsalicylic acid was partially biodegradable (98% and 65% degradation, respectively). The persistence of dichloromethane, ofloxacin and hidrochlorothiazide was confirmed along the 28 days of the Zahn-Wellens test whereas 1,1,1-trichloroethane showed inherent biodegradability (74% removal). Most of the chlorinated compounds, pharmaceuticals, bisphenol A and ethylenediaminetetraacetic acid were partially degraded in 28 d with total organic carbon (TOC) reduction ranging from 21% to 51%. Sulphamethoxazole showed certain biodegradation (50% removal) with TOC decrease around 31%, which indicates the formation of non-biodegradable by-products.

Evaluation of 90-day inhalation toxicity of petroleum and oil-shale diesel fuel marine (DFM). Final technical report, November 1977-January 1985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaworski, C.L.; MacEwen, J.D.; Vernot, E.H.

1985-12-01

Subchronic 90-day inhalation toxicity studies were conducted to compare the toxicity of petroleum and oil-shale-derived diesel fuel marine (DFM). Beagle dogs, Fischer 344 rats, and C57BL/6 mice were continuously exposed to DFM at concentrations of 50 mg/cu. m and 300 mg/cu. m. Unexposed controls were also maintained. All dogs and a portion of each rodent group were sacrificed and examined at exposure termination. The remaining rodents were held for observation up to 21 months postexposure. Male rats exposed to DFM for 90 days developed nephrotoxic changes characterized by hyaline degeneration, necrosis, and intratubular cysts. Subsequently, male rats exposed to 300more » mg/cu. m DFM developed mineralization and papillary hyperplasia. These postexposure renal changes were generally less severe in male rats exposed to 50 mg/cu. m Shale DFM and were absent in male rats exposed to 50 mg/cu. m Petroleum DFM. Female rats as well as dogs and mice exposed to DFM were free of significant renal damage. Mild reductions in body-weight gains and erythrocyte parameters were also noted in male rats exposed to DFM. Neither material produced significant tumor formation in any species tested. The results of this study are consistent with the effects noted in other hydrocarbon-fuel toxicity studies. Comparison of the effects observed in these studies with petroleum or shale suggest only minor differences between the two materials.« less

Oral acute toxic class method: a successful alternative to the oral LD50 test.

PubMed

Schlede, Eva; Genschow, Elke; Spielmann, Horst; Stropp, Gisela; Kayser, Detlev

2005-06-01

The oral acute toxic class method (ATC method) was developed as an alternative to replace the oral LD50 test. The ATC method is a sequential testing procedure using only three animals of one sex per step at any of the defined dose levels. Depending on the mortality rate three but never more than six animals are used per dose level. This approach results in the reduction of numbers of animals used in comparison to the LD50 test by 40-70%. The principle of the oral ATC method is based on the Probit model and it was first evaluated on a biometric basis before a national and subsequently an international ring study were conducted. The results demonstrated an excellent agreement between the toxicity and the animal numbers predicted biometrically and observed in the validation studies. The oral ATC method was adopted as an official test guideline by OECD in 1996 and was slightly amended in 2001. The ATC method has been successfully used in Germany and in 2003 >85% of all tests on acute oral toxicity testing was conducted as oral ATC tests. In member states of the European Union the ATC method is used in the range of 50% of all tests conducted. Meanwhile the oral LD50 test has been deleted by OECD, by the European Union and by the USA, making the use of alternatives to the oral LD50 test mandatory.

Assessment of Cost Impacts of Using Non-Toxic Propulsion in Satellites

NASA Astrophysics Data System (ADS)

Schiebener, P. J.; Gies, O.; Stuhlberger, J.; Schmitz, H.-D.

2002-01-01

The growing costs of space missions, the need for increased mission performance, and concerns associated with environmental issues deeply influence propulsion system design and propellant selection criteria. A propellant's performance was defined in the past exclusively in terms of specific impulse and density, but now high-performance, non-toxic, non-sophisticated mono- propellant systems are key drivers, and are considered for development to replace the traditional hydrazine (N2H4) mono-propellant thrusters. The mono-propellants under consideration are propellant formulations, which should be environmentally friendly, should have a high density, equal or better performance and better thermal characteristics than hydrazine. These considerations raised interest specially in the candidates of Hydroxylammonium Nitrate (HAN)-based propellants, Ammoniumdinitramide (ADN)-based propellants, Tri-ethanol (TEAN)-based propellants, Hydrazinium Nitroformate (HNF)-based propellants, Hydrogen Peroxide (H2O2)-based propellants. A near-term objective in consideration of satellite related process optimisation is to significantly reduce on-ground operations costs and at the same time improve mission performance. A far-term objective is to obtain a system presenting a very high performance, illustrated by a high specific impulse. Moving to a "non-toxic" propulsion system seems to be a solution to these two goals. The sought after benefits for non-toxic spacecraft mono-propellant propulsion are under investigation taking into account the four main parameters which are mandatory for customer satisfaction while meeting the price constraints: - Reliability, availability, maintainability and safety, - Manufacturing, assembly, integration and test, - Launch preparation and support, - Ground support equipment. These benefits of non-toxic mono-propellants can be proven by various examples, like an expected reduction of development costs due the non-toxicity of propellants which might allow "easier" design, reducing some inhibits for ground safety, leading to a shorter development time, and consequently to reduced program costs. Operational costs could be reduced due to the use of non-toxic propellant. Their non-toxicity, in comparison to the traditional propellants, will avoid special safety procedures and also parallelisation of processes during all phases of AIT and launch preparations. The costs directly associated with propellant handling, transport and storage should be lower, also follow-on costs risk is minimised because of the elimination or significant reduction of toxic and carcinogenic characteristics of the propellants. The physical characteristic and properties of some of the propellants formulations mentioned, like a higher density than hydrazine, support the beneficial aspects: a global S/C weight reduction could be achieved due to smaller tanks.

Fluconazole prophylaxis in preterm infants: a systematic review.

PubMed

Rios, Juliana Ferreira da Silva; Camargos, Paulo Augusto Moreira; Corrêa, Luísa Petri; Romanelli, Roberta Maia de Castro

This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Efficacy of osthole for Echinococcus granulosus in vitro and Echinococcus multilocularis in vivo.

PubMed

Yuan, Miaomiao; Luo, Yanping; Xin, Qi; Gao, Haijun; Zhang, Guochao; Jing, Tao

2016-08-15

Echinococcosis is a zoonotic infection caused by cestode species of the genus Echinococcus; in addition, this zoonosis has long been neglected as a parasitic disease and has limited treatment options. Clinical drugs such as benzimidazole derivatives have limited treatment efficacy. The current study evaluated a novel drug, osthole, with low toxicity and high activity against Echinococcus in vitro and in vivo. The results in vitro indicated that the viability of Echinococcus granulosus protoscoleces in the group treated with osthole (120μM) decreased by 100% within 3days. In vivo experiments were conducted using parasite-infected mice. For this purpose, three groups of infected mice were treated daily for 6 weeks with albendazole (ABZ, 100mg/kg, positive control group), osthole (100mg/kg, experimental group), or honey/PBS (100mg/kg, negative control group), respectively. The osthole- and ABZ-treated groups presented a significant reduction in wet weight of metacestodes, increase in the level of interleukin (IL)-4 and the percentage of eosinophils compared with the control group. Osthole exhibited a high activity against echinococcosis in vivo. In addition, the toxicity of osthole was evaluated via an in vitro 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, as well as via morphological observation and calculation of liver and kidney function indexes in vivo. No obvious toxic effects of osthole were observed in our study. Therefore, this novel drug may be a promising alternative to benzimidazole in anti-echinococcosis chemotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanosized aluminum altered immune function.

PubMed

Braydich-Stolle, Laura K; Speshock, Janice L; Castle, Alicia; Smith, Marcus; Murdock, Richard C; Hussain, Saber M

2010-07-27

On the basis of their uses in jet fuels and munitions, the most likely scenario for aluminum nanoparticle (NP) exposure is inhalation. NPs have been shown to be capable of penetrating deep into the alveolar regions of the lung, and therefore human alveolar macrophages (U937) with human type II pneumocytes (A549) were cultured together and exposed to NPs dispersed in an artificial lung surfactant to more accurately mimic the lung microenvironment. Two types of NPs were evaluated: aluminum (Al) and aluminum oxide (Al2O3). Following a 24-h incubation, cell viability was assessed using MTS, and mild toxicity was observed at higher doses with the U937 cells affected more than the A549. Since the U937 cells provided protection from NP toxicity, the cocultures were exposed to a benign concentration of NPs and infected with the respiratory pathogen community-associated methicillin-resistant Staphylococcus aureus (ca-MRSA) to determine any changes in cellular function. Phagocytosis assays demonstrated that the NPs impaired phagocytic function, and bacterial growth curves confirmed that this reduction in phagocytosis was not related to NP-bacteria interactions. Furthermore, NFkappaB PCR arrays and an IL-6 and TNF-alpha real time PCR demonstrated that both types of NPs altered immune response activation. This change was confirmed by ELISA assays that evaluated the secretion of IL-6, IL-8, IL-10, IL-1beta, and TNF-alpha and illustrated that the NPs repressed secretion of these cytokines. Therefore, although the NPs were not toxic to the cells, they did impair the cell's natural ability to respond to a respiratory pathogen regardless of NP composition.

FIELD VALIDATION OF SEDIMENT TOXCITY IDENTIFCATION AND EVALUATION METHODS

EPA Science Inventory

Sediment Toxicity Identification and Evaluation (TIE) methods have been developed for both porewaters and whole sediments. These relatively simple laboratory methods are designed to identify specific toxicants or classes of toxicants in sediments; however, the question of whethe...

76 FR 7841 - Agency Information Collection Activities; Proposed Collections; Toxic Chemical Release Reporting...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... prevention and waste management data, including recycling information, for such chemicals. 42 U.S.C. 13106... reporting forms and associated instructions, but these changes are estimated to have a negligible effect on... source reduction activities, and provide additional optional information on source reduction, recycling...

ENDOGENOUS REDUCTANTS SUPPORT THE CATALYTIC FUNCTION OF REOMBINANT RAT CYT119, AN ARSENIC METHYLTRANSFERASE

EPA Science Inventory

The postulated scheme for the metabolism of inorganic As involves alternating steps of oxidative methylation and of reduction of As from the pentavalent to the trivalent oxidation state, producing methylated compounds containing AsIII that are highly reactive and toxic. S-adenosy...

An integrated vegetated ditch system reduces chlorpyrifos loading in agricultural runoff.

PubMed

Phillips, Bryn M; Anderson, Brian S; Cahn, Michael; Rego, Jessa L; Voorhees, Jennifer P; Siegler, Katie; Zhang, Xuyang; Budd, Robert; Goh, Kean; Tjeerdema, Ron S

2017-03-01

Agricultural runoff containing toxic concentrations of the organophosphate pesticide chlorpyrifos has led to impaired water body listings and total maximum daily load restrictions in California's central coast watersheds. Chlorpyrifos use is now tightly regulated by the Central Coast Regional Water Quality Control Board. This study evaluated treatments designed to reduce chlorpyrifos in agricultural runoff. Initial trials evaluated the efficacy of 3 different drainage ditch installations individually: compost filters, granulated activated carbon (GAC) filters, and native grasses in a vegetated ditch. Treatments were compared to bare ditch controls, and experiments were conducted with simulated runoff spiked with chlorpyrifos at a 1.9 L/s flow rate. Chlorpyrifos concentrations and toxicity to Ceriodaphnia dubia were measured at the input and output of the system. Input concentrations of chlorpyrifos ranged from 858 ng/L to 2840 ng/L. Carbon filters and vegetation provided the greatest load reduction of chlorpyrifos (99% and 90%, respectively). Toxicity was completely removed in only one of the carbon filter trials. A second set of trials evaluated an integrated approach combining all 3 treatments. Three trials were conducted each at 3.2 L/s and 6.3 L/s flow rates at input concentrations ranging from 282 ng/L to 973 ng/L. Chlorpyrifos loadings were reduced by an average of 98% at the low flow rate and 94% at the high flow rate. Final chlorpyrifos concentrations ranged from nondetect (<50 ng/L) to 82 ng/L. Toxicity to C. dubia was eliminated in 3 of 6 integrated trials. Modeling of the ditch and its components informed design alterations that are intended to eventually remove up to 100% of pesticides and sediment. Future work includes investigating the adsorption capacity of GAC, costs associated with GAC disposal, and real-world field trials to further reduce model uncertainties and confirm design optimization. Trials with more water-soluble pesticides such as neonicotinoids are also recommended. Integr Environ Assess Manag 2017;13:423-430. © 2016 SETAC. © 2016 SETAC.

Potential applications of Pseudomonas sp. (strain CPSB21) to ameliorate Cr6+ stress and phytoremediation of tannery effluent contaminated agricultural soils.

PubMed

Gupta, Pratishtha; Rani, Rupa; Chandra, Avantika; Kumar, Vipin

2018-03-20

Contamination of agricultural soil with heavy metals has become a serious concern worldwide. In the present study, Cr 6+ resistant plant growth promoting Pseudomonas sp. (strain CPSB21) was isolated from the tannery effluent contaminated agricultural soils and evaluated for the plant growth promoting activities, oxidative stress tolerance, and Cr 6+ bioremediation. Assessment of different plant growth promotion traits, such as phosphate solubilization, indole-3-acetic acid production, siderophores, ammonia and hydrogen cyanide production, revealed that the strain CPSB21 served as an efficient plant growth promoter under laboratory conditions. A pot experiment was performed using sunflower (Helianthus annuus L.) and tomato (Solanum lycopersicum L.) as a test crop. Cr 6+ toxicity reduced plant growth, pigment content, N and P uptake, and Fe accumulation. However, inoculation of strain CPSB21 alleviated the Cr 6+ toxicity and enhanced the plant growth parameters and nutrient uptake. Moreover, Cr toxicity had varied response on oxidative stress tolerance at graded Cr 6+ concentration on both plants. An increase in superoxide dismutase (SOD) and catalase (CAT) activity and reduction in malonialdehyde (MDA) was observed on inoculation of strain CPSB21. Additionally, inoculation of CPSB21 enhanced the uptake of Cr 6+ in sunflower plant, while no substantial enhancement was observed on inoculation in tomato plant.

Nutritional evaluation of silage made from the toxic weed Parthenium hysterophorus in animals.

PubMed

Narasimhan, T R; Murthy, B S; Rao, P V

1993-07-01

After ensilation, the toxic Compositae weed Parthenium hysterophorus was devoid of the toxic principle parthenin. Laboratory-scale ensilation indicated that no parthenin was detectable after 5 wk of anaerobic fermentation. For animal feeding studies, silage was made on a large scale from Parthenium mixed with maize or from Parthenium alone. Crossbred bull and buffalo bull calves were fed diets containing the silages, or control diet without silage, for 12 wk. The animals consumed both silages with relish, and body weight gains of silage-fed calves did not differ from those of the controls. The digestibilities of dry matter, fibre and nitrogen-free extract were greater with the control diet, but the biological value of proteins tended to be greater with the silage-containing diets. Haematological studies indicated no significant differences between experimental and control groups in selected parameters, except for a reduction in blood urea nitrogen in the animals fed silage. The possible causes for these biochemical alterations are discussed. Since the nutritive value of Parthenium silage compares favourably with the standard diet, and Parthenium seeds collected from the silage did not germinate, we suggest that ensilation can be used as an additional method in the containment and eradication of these plants, which grow wild in India.

Mixture effects of benzene, toluene, ethylbenzene, and xylenes (BTEX) on lung carcinoma cells via a hanging drop air exposure system.

PubMed

Liu, Faye F; Escher, Beate I; Were, Stephen; Duffy, Lesley; Ng, Jack C

2014-06-16

A recently developed hanging drop air exposure system for toxicity studies of volatile chemicals was applied to evaluate the cell viability of lung carcinoma A549 cells after 1 and 24 h of exposure to benzene, toluene, ethylbenzene, and xylenes (BTEX) as individual compounds and as mixtures of four or six components. The cellular chemical concentrations causing 50% reduction of cell viability (EC50) were calculated using a mass balance model and came to 17, 12, 11, 9, 4, and 4 mmol/kg cell dry weight for benzene, toluene, ethylbenzene, m-xylene, o-xylene, and p-xylene, respectively, after 1 h of exposure. The EC50 decreased by a factor of 4 after 24 h of exposure. All mixture effects were best described by the mixture toxicity model of concentration addition, which is valid for chemicals with the same mode of action. Good agreement with the model predictions was found for benzene, toluene, ethylbenzene, and m-xylene at four different representative fixed concentration ratios after 1 h of exposure, but lower agreement with mixture prediction was obtained after 24 h of exposure. A recreated car exhaust mixture, which involved the contribution of the more toxic p-xylene and o-xylene, yielded an acceptable, but lower quality, prediction as well.

Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maclean, Jillian, E-mail: jillian.maclean@uclh.nhs.uk; Fersht, Naomi; Bremner, Fion

2013-03-15

Purpose: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. Methods and Materials: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. Results: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16more » patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. Conclusion: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.« less

Tissue lead concentration during chronic exposure of Pimephales promelas (fathead minnow) to lead nitrate in aquarium water.

PubMed

Spokas, Eric G; Spur, Bernd W; Smith, Holly; Kemp, Francis W; Bogden, John D

2006-11-01

The fathead minnow is a useful species for evaluating the toxicity of wastewater effluents. While this fish is widely used for "survival" studies of metal toxicity, little or no work has been done on the tissue distribution of metals in fathead minnows. To determine the distribution of tissue lead, aquarium studies were conducted for several weeks with fish maintained in soft synthetic freshwater. Lead- (II) nitrate was added to three aquaria attaining concentrations of 20-30 ppb (aquarium B), 100-140 ppb (aquarium C), and roughly 200 ppb (aquarium D). Results were compared to controls (aquarium A). During the initial week, the majority of aquarium D fish died, whereas few deaths occurred in the other groups. Lead accumulation was dose- and tissue-dependent, with highest uptake by the gills. Gill concentrations of aquarium D fish averaged about 4-fold higherthan in skeleton or skin and muscle. In vitro, lead (2.5-25 ppm) caused dose-dependent reductions in the ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) in gills incubated in physiological buffer. These findings demonstrate that fathead minnow gills bind and accumulate waterborne lead rapidly and preferentially and raise the possibility that gill lipid peroxidation contributes to lead toxicity at low water hardness.

Abrin Toxicity and Bioavailability after Temperature and pH Treatment.

PubMed

Tam, Christina C; Henderson, Thomas D; Stanker, Larry H; He, Xiaohua; Cheng, Luisa W

2017-10-13

Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), Abrus precatorius and is a potential bioterror weapon. The temperature and pH stability of abrin was evaluated with an in vitro cell free translation (CFT) assay, a Vero cell culture cytotoxicity assay, and an in vivo mouse bioassay. pH treatment of abrin had no detrimental effect on its stability and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing temperatures did not completely abrogate protein translation. In both the cell culture cytotoxicity model and the mouse bioassay, abrin's toxic effects were completely abrogated if the toxin was exposed to temperatures of 74 °C or higher. In the cell culture model, 63 °C-treated abrin had a 30% reduction in cytotoxicity which was validated in the in vivo mouse bioassay with all mice dying but with a slight time-to-death delay as compared to the non-treated abrin control. Since temperature inactivation did not affect abrin's ability to inhibit protein synthesis (A-chain), we hypothesize that high temperature treatment affected abrin's ability to bind to cellular receptors (affecting B-chain). Our results confirm the absolute need to validate in vitro cytotoxicity assays with in vivo mouse bioassays.

Abrin Toxicity and Bioavailability after Temperature and pH Treatment

PubMed Central

Tam, Christina C.; Henderson, Thomas D.; Stanker, Larry H.; He, Xiaohua; Cheng, Luisa W.

2017-01-01

Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), Abrus precatorius and is a potential bioterror weapon. The temperature and pH stability of abrin was evaluated with an in vitro cell free translation (CFT) assay, a Vero cell culture cytotoxicity assay, and an in vivo mouse bioassay. pH treatment of abrin had no detrimental effect on its stability and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing temperatures did not completely abrogate protein translation. In both the cell culture cytotoxicity model and the mouse bioassay, abrin’s toxic effects were completely abrogated if the toxin was exposed to temperatures of 74 °C or higher. In the cell culture model, 63 °C-treated abrin had a 30% reduction in cytotoxicity which was validated in the in vivo mouse bioassay with all mice dying but with a slight time-to-death delay as compared to the non-treated abrin control. Since temperature inactivation did not affect abrin’s ability to inhibit protein synthesis (A-chain), we hypothesize that high temperature treatment affected abrin’s ability to bind to cellular receptors (affecting B-chain). Our results confirm the absolute need to validate in vitro cytotoxicity assays with in vivo mouse bioassays. PMID:29027937

Acute and subchronic toxicological evaluation of Mequindox in Wistar rats.

PubMed

Ihsan, Awais; Wang, Xu; Huang, Xian-ju; Liu, Yu; Liu, Qin; Zhou, Wen; Yuan, Zong-hui

2010-01-01

We studied an acute and subchronic oral toxicity of Mequindox (MEQ), a quinoxaline 1,4-dioxide antimicrobial promoter, in Wistar rats according to OECD guidelines. For acute toxicity study, single doses of MEQ at 175, 550 and 2000 mg/kg b.w. were administered to rats by oral gavage. The calculated LD(50) was 550 mg/kg b.w. In subchronic study, rats were fed diets containing 0, 55, 110 or 275 mg MEQ/kg. There was a reduction in body weight of rats fed 275 mg MEQ/kg diet. At 90 days autopsy, a significant decrease in the kidney weight was observed in males while an increase in relative liver and adrenal weights were observed in females fed 275 mg MEQ/kg diet. There was a significant increased in alanineaminotransferase (ALT) and malondialdehyde (MDA) concentrations in males, superoxide dismutase (SOD) activities in females, and aspartateaminotransferase (AST) levels in serum of both genders fed 275 mg MEQ/kg diet. Other toxic effects of 275 mg MEQ/kg diet included significant decrease in sodium and significant increase in potassium concentrations in serum in both genders. We may conclude that MEQ can induce hepatic and adrenal histological changes as well as leaking of different serum constituents in Wistar rats. Copyright 2010 Elsevier Inc. All rights reserved.

Bioventing remediation and ecotoxicity evaluation of phenanthrene-contaminated soil.

PubMed

García Frutos, F Javier; Escolano, Olga; García, Susana; Babín, Mar; Fernández, M Dolores

2010-11-15

The objectives of soil remediation processes are usually based on threshold levels of soil contaminants. However, during remediation processes, changes in bioavailability and metabolite production can occur, making it necessary to incorporate an ecotoxicity assessment to estimate the risk to ecological receptors. The evolution of contaminants and soil ecotoxicity of artificially phenanthrene-contaminated soil (1000 mg/kg soil) during soil treatment through bioventing was studied in this work. Bioventing was performed in glass columns containing 5.5 kg of phenanthrene-contaminated soil and uncontaminated natural soil over a period of 7 months. Optimum conditions of mineralisation (humidity=60% WHC; C/N/P=100:20:1) were determined in a previous work. The evolution of oxygen consumption, carbon dioxide production, phenanthrene concentration and soil toxicity were studied on sacrificed columns at periods of 0, 3 and 7 months. Toxicity to soil and aquatic organisms was determined using a multispecies system in the soil columns (MS-3). In the optimal bioventing treatability test, we obtained a reduction rate in phenanthrene concentration higher that 93% after 7 months of treatment. The residual toxicity obtained at the end of the treatment was not attributed to the low phenanthrene concentration, but to the ammonia used to restore the optimal C/N ratio. Copyright © 2010 Elsevier B.V. All rights reserved.

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

PubMed

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.

Fate and effects of picric acid and 2,6-DNT in marine environments: toxicity of degradation products.

PubMed

Nipper, Marion; Carr, R Scott; Biedenbach, James M; Hooten, Russell L; Miller, Karen

2005-11-01

The toxicity of transformation products of 2,6-dinitrotoluene (2,6-DNT) and 2,4,6-trinitrophenol (picric acid) were assessed in spiked sandy and fine-grained marine sediments and in seawater. Toxicity of pore water from sediments spiked with 2,6-DNT decreased for the macro-alga, Ulva fasciata, zoospores as biotransformation proceeded, but increased for the copepod, Schizopera knabeni, nauplii. The primary biotransformation product of 2,6-DNT, 2-amino-6-nitrotoluene, was also more toxic than the parent compound to copepod nauplii, but not to alga zoospores, in spiked seawater tests. Two biotransformation products of picric acid, picramic acid and 2,4-DNP, were more toxic than their parent compound. Porewater toxicity from picric acid-spiked sediments decreased significantly at the end of six-months incubation. Fine-grained sediment spiked with either ordnance compound had lower toxicity than its sandy counterpart after six months, suggesting faster microbial transformation in the former and production of less toxic products. Photo-transformation of 2,6-DNT in seawater resulted in a reduction in toxicity.

Spatial Evaluation of Heavy Metals Concentrations in the Surface Sediment of Taihu Lake.

PubMed

Niu, Yong; Jiao, Wei; Yu, Hui; Niu, Yuan; Pang, Yong; Xu, Xiangyang; Guo, Xiaochun

2015-11-27

With regard to the size of China's freshwater lakes, Taihu Lake ranks third and it plays an important role in the supply of drinking water, flood prevention, farming and navigation, as well as in the travelling industry. The problem of environmental pollution has attracted widespread attention in recent years. In order to understand the levels, distribution and sources of heavy metals in sediments of Taihu Lake, random selection was carried out to obtain 59 samples of surface sediment from the entire lake and study the concentrations of Pb, Cd, Cu, Zn, Cr and Ni. Toxic units were also calculated to normalize the toxicities caused by various heavy metals. As a result, Cd and Cu in sediment were considered lower than the effect range low (ERL) at all regions where samples were gathered, while Pb and Ni were categorized into ERL-effect range median (ERM) at over 22% of the regions where samples were obtained. Nevertheless, all average concentrations of the samples were below the level of potential effect. According to the findings of this research, significant spatial heterogeneity existed in the above heavy metals. In conclusion, the distribution areas of heavy metals with higher concentrations were mainly the north bays, namely Zhushan Bay, Meiliang Bay as well as Gonghu Bay. The distribution areas of Cu, Zn, Cr and Ni with higher concentration also included the lake's central region, whereas the uniform distribution areas of those with lower concentrations were the lake's southeast region. In addition, it was most probable that the spatial distribution of heavy metals was determined by river inputs, whereas atmospheric precipitation caused by urban and traffic contamination also exerted considerable effects on the higher concentrations of Pb and Cd. Through evaluating the total amount of toxic units (ΣTU), it was found that higher toxicity existed primarily in the north bays and central region of the lake. If the heavy metals were sorted by the reduction of mean heavy metal toxic units in Taihu Lake in descending order, it would be Pb, Cr, Ni, Cd, Zn and Cu. Generally speaking, these result of analyses are conducive to alleviating the contamination of heavy metals in Taihu Lake.

NRG Oncology Radiation Therapy Oncology Group 0822: A Phase 2 Study of Preoperative Chemoradiation Therapy Using Intensity Modulated Radiation Therapy in Combination With Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Theodore S., E-mail: tshong1@mgh.harvard.edu; Moughan, Jennifer; Garofalo, Michael C.

Purpose: To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials: Patients with localized, nonmetastatic T3 or T4 rectal cancer <12 cm from the anal verge were enrolled in a prospective, multi-institutional, single-arm study of preoperative chemoradiation. Patients received 45 Gy with IMRT in 25 fractions, followed by a 3-dimensional conformal boost of 5.4 Gy in 3 fractions with concurrent capecitabine/oxaliplatin (CAPOX). Surgery was performed 4 to 8 weeks after the completion of therapy. Patients were recommended to receive FOLFOX chemotherapy after surgery. The primary endpoint ofmore » the study was acute grade 2 to 5 GI toxicity. Seventy-one patients provided 80% probability to detect at least a 12% reduction in the specified GI toxicity with the treatment of CAPOX and IMRT, at a significance level of .10 (1-sided). Results: Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion: The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.« less

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

PubMed Central

2013-01-01

Background Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications. PMID:23414068

A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.

PubMed

Aquea, Felipe; Federici, Fernan; Moscoso, Cristian; Vega, Andrea; Jullian, Pastor; Haseloff, Jim; Arce-Johnson, Patricio

2012-04-01

Boron is an essential micronutrient for plants and is taken up in the form of boric acid (BA). Despite this, a high BA concentration is toxic for the plants, inhibiting root growth and is thus a significant problem in semi-arid areas in the world. In this work, we report the molecular basis for the inhibition of root growth caused by boron. We show that application of BA reduces the size of root meristems, correlating with the inhibition of root growth. The decrease in meristem size is caused by a reduction of cell division. Mitotic cell number significantly decreases and the expression level of key core cell cycle regulators is modulated. The modulation of the cell cycle does not appear to act through cytokinin and auxin signalling. A global expression analysis reveals that boron toxicity induces the expression of genes related with abscisic acid (ABA) signalling, ABA response and cell wall modifications, and represses genes that code for water transporters. These results suggest that boron toxicity produces a reduction of water and BA uptake, triggering a hydric stress response that produces root growth inhibition. © 2011 Blackwell Publishing Ltd.

Effects of the filamentous cyanobacterium Nodularia on fitness and feeding behavior of young-of-the-year (YOY) Eurasian perch (Perca fluviatilis).

PubMed

Persson, Karl-Johan; Stenroth, Patrik; Legrand, Catherine

2011-06-01

This study reveals that both cyanobacterial toxicity and turbidity have the potential to reduce the growth and energy storage of young-of-the-year (YOY) perch and thereby influence survival rates. During the 1990's a reduction in recruitment of YOY perch (Perca fluviatilis) occurred along the Swedish East coast. Concurrently, large blooms of filamentous cyanobacteria have increased in the Baltic Proper and in coastal waters. This study examined whether extended exposure to toxic and non-toxic filamentous cyanobacterium Nodularia affect YOY perch growth and feeding behavior under simulated bloom conditions (30 days at 50 μg Chl a L(-1)). Specific growth rate (SGR), the somatic condition index (SCI) and the lipid content of YOY perch (10-12 weeks old) were significantly lower in perch exposed to Nodularia compared to fed controls (no Nodularia). YOY perch exposed to non-toxic Nodularia displayed a higher attack rate than perch living in Nodularia free controls in 2 out of 3 trials. Reductions in growth and energy storage, mediated by cyanobacteria, increase the risk of starvation and predation and could locally influence recruitment of YOY perch. Copyright © 2011 Elsevier Ltd. All rights reserved.

Refinement, Reduction, and Replacement of Animal Toxicity Tests by Computational Methods.

PubMed

Ford, Kevin A

2016-12-01

Widespread public and scientific interest in promoting the care and well-being of animals used for toxicity testing has given rise to improvements in animal welfare practices and views over time, as well as laws and regulations that support means to reduce, refine, and replace animal use (known as the 3Rs) in certain toxicity studies. One way these regulations continue to achieve their aim is by promoting the research, development, and application of alternative testing approaches to characterize potential toxicities either without animals or with minimal use. An important example of an alternative approach is the use of computational toxicology models. Along with the potential capacity to reduce or replace the use of animals for the assessment of particular toxicological endpoints, computational models offer several advantages compared to in vitro and in vivo approaches, including cost-effectiveness, rapid availability of results, and the ability to fully standardize procedures. Pharmaceutical research incorporating the use of computational models has increased steadily over the past 15 years, likely driven by the motivation of companies to screen out toxic compounds in the early stages of development. Models are currently available to aid in the prediction of several important toxicological endpoints, including mutagenicity, carcinogenicity, eye irritation, hepatotoxicity, and skin sensitization, albeit with varying degrees of success. This review serves to introduce the concepts of computational toxicology and evaluate their role in the safety assessment of compounds, while also highlighting the application of in silico methods in the support of the goal and vision of the 3Rs. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research.All rights reserved. For permissions, please email: journals.permissions@oup.com.

Acute toxicity study of cisplatin loaded long-circulating and pH-sensitive liposomes administered in mice.

PubMed

Leite, Elaine A; Lana, Angela M Q; Junior, Alvaro D Carvalho; Coelho, Luiz G V; De Oliveira, Mônica C

2012-04-01

Cisplatin (CDDP) is a very active and cytotoxic agent but causes severe side effects, namely nephrotoxicity, which limits the therapy. The present study aimed to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), as compared to free CDDP, after their intravenous administration in mice. After the administration of free CDDP or SpHL-CDDP at different doses, the body weight was recorded and the LD50 and the maximum tolerated dose (MTD) were calculated. Blood samples were collected for hematological and biochemical analysis. Kidneys, liver, spleen, and bone marrow were removed for histopathological examination. A reduction of body weight of less than 15% could be observed in male and female mice after treatment with free CDDP and SpHL-CDDP at doses of < or = 10 mg/kg and 20 mg/kg, respectively. The LD50 and MTD values obtained after SpHL-CDDP administration were approximately two and three times higher, respectively, than those obtained using free CDDP. Changes in hematological parameters and hematopoietic tissue morphology showed the appearance of toxicity induced by free CDDP. By contrast, the absence of mielotoxicity after SpHL-CDDP treatment could be observed. As regards nephrotoxicity, no alteration in blood urea and creatinine levels, nor morphological change in kidneys, could be observed in mice treated with SpHL-CDDP, as compared to saline-treatment control group. The results showed that SpHL-CDDP at its MTD (20 mg/kg), as compared to the administration of free CDDP at its MTD (7.5 mg/kg), significantly reduced the renal toxicity. Thus, SpHL-CDDP can eliminate CDDP-induced toxicity and is a promising candidate for the intravenous therapy of solid tumors.

An evaluation of inorganic toxicity reference values for use in assessing hazards to American robins (Turdus migratorius).

PubMed

Beyer, W Nelson; Sample, Bradley E

2017-03-01

When performing screening-level and baseline risk assessments, assessors usually compare estimated exposures of wildlife receptor species with toxicity reference values (TRVs). We modeled the exposure of American robins (Turdus migratorius) to 10 elements (As, Cd, Cr, Cu, Hg, Mn, Pb, Se, Zn, and V) in spring and early summer, a time when earthworms are the preferred prey. We calculated soil benchmarks associated with possible toxic effects to these robins from 6 sets of published TRVs. Several of the resulting soil screening-level benchmarks were inconsistent with each other and less than soil background concentrations. Accordingly, we examined the derivations of the TRVs as a possible source of error. In the case of V, a particularly toxic chemical compound (ammonium vanadate) containing V, not normally present in soil, had been used to estimate a TRV. In the cases of Zn and Cu, use of uncertainty values of 10 in estimating TRVs led to implausibly low soil screening values. In the case of Pb, a TRV was calculated from studies demonstrating reductions in egg production in Japanese quail (Coturnix coturnix japonica) exposed to Pb concentrations well below than those causing toxic effects in other species of birds. The results on quail, which were replicated in additional trials, are probably not applicable to other, unrelated species, although we acknowledge that only a small fraction of all species of birds has been tested. These examples underscore the importance of understanding the derivation and relevance of TRVs before selecting them for use in screening or in ecological risk assessment. Integr Environ Assess Manag 2017;13:352-359. © 2016 SETAC. © 2016 SETAC.

Y1-receptor-ligand-functionalized ultrasmall upconversion nanoparticles for tumor-targeted trimodality imaging and photodynamic therapy with low toxicity.

PubMed

Yu, Zhangsen; Xia, Yuanzhi; Xing, Jie; Li, Zihou; Zhen, Jianjun; Jin, Yinhua; Tian, Yuchen; Liu, Chuang; Jiang, Zhenqi; Li, Juan; Wu, Aiguo

2018-05-31

Achieving efficient photodynamic therapy (PDT) in deeper biological tissue is still the biggest bottleneck that limits its widespread application in clinic. Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with particle-size-induced upconversion fluorescence (UF) reduction and the related in vivo toxicity still cannot be solved properly. In this study, we synthesized Y1Rs-ligand [Pro30, Nle31, Bpa32, Leu34]NPY(28-36) (NPY)-modified and photosensitizer MC540-loaded LiLuF4:Yb,Er@nLiGdF4@mSiO2 multifunctional nanocomposites (MNPs) with a core-multishell structure and ultrasmall size. Their in vitro and in vivo breast tumor targeting, trimodality imaging performance, PDT therapeutic efficacy, and acute toxicity were evaluated. Our results demonstrated that the core-multishell MNPs(MC540) could achieve excellent UF imaging, and that doping with Gd3+ and Lu3+ rare earth ions could enhance the MR and CT imaging performance. In addition, the mSiO2 shell provided a higher loading rate for the photosensitizer MC540, and the DSPE-PEG thin layer coating outside the MNPs(MC540) further improved the water solubility and biocompatibility, reducing the acute toxicity of the nanocomposites. Finally, the NPY modification enhanced the targetability of MNPs(MC540)/DSPE-PEG-NPY to breast tumors, improving the trimodality UF, CT, and MR imaging performance and PDT efficacy for Y1-receptor-overexpressed breast cancer. In general, our developed multifunctional nanocomposites can serve as a theranostic agent with low toxicity, providing great potential for their use in clinical breast cancer diagnosis and therapy.

Ketamine Causes Mitochondrial Dysfunction in Human Induced Pluripotent Stem Cell-Derived Neurons

PubMed Central

Ito, Hiroyuki; Uchida, Tokujiro; Makita, Koshi

2015-01-01

Purpose Ketamine toxicity has been demonstrated in nonhuman mammalian neurons. To study the toxic effect of ketamine on human neurons, an experimental model of cultured neurons from human induced pluripotent stem cells (iPSCs) was examined, and the mechanism of its toxicity was investigated. Methods Human iPSC-derived dopaminergic neurons were treated with 0, 20, 100 or 500 μM ketamine for 6 and 24 h. Ketamine toxicity was evaluated by quantification of caspase 3/7 activity, reactive oxygen species (ROS) production, mitochondrial membrane potential, ATP concentration, neurotransmitter reuptake activity and NADH/NAD+ ratio. Mitochondrial morphological change was analyzed by transmission electron microscopy and confocal microscopy. Results Twenty-four-hour exposure of iPSC-derived neurons to 500 μM ketamine resulted in a 40% increase in caspase 3/7 activity (P < 0.01), 14% increase in ROS production (P < 0.01), and 81% reduction in mitochondrial membrane potential (P < 0.01), compared with untreated cells. Lower concentration of ketamine (100 μM) decreased the ATP level (22%, P < 0.01) and increased the NADH/NAD+ ratio (46%, P < 0.05) without caspase activation. Transmission electron microscopy showed enhanced mitochondrial fission and autophagocytosis at the 100 μM ketamine concentration, which suggests that mitochondrial dysfunction preceded ROS generation and caspase activation. Conclusions We established an in vitro model for assessing the neurotoxicity of ketamine in iPSC-derived neurons. The present data indicate that the initial mitochondrial dysfunction and autophagy may be related to its inhibitory effect on the mitochondrial electron transport system, which underlies ketamine-induced neural toxicity. Higher ketamine concentration can induce ROS generation and apoptosis in human neurons. PMID:26020236

Study of the degradation performance (TOC, BOD, and toxicity) of bisphenol A by the photo-Fenton process.

PubMed

Pérez-Moya, M; Kaisto, T; Navarro, M; Del Valle, L J

2017-03-01

Degradation of bisphenol A (BPA, 0.5 L, 30 mg L -1 ) was studied by photo-Fenton treatment, while Fenton reagents were variables. The efficiency of the degradation process was evaluated by the reduction of total organic carbon (TOC), the biochemical oxygen demand (BOD), and toxicity. For toxicity analysis, bacterial methods were found infeasible, but the in vitro assay of VERO cells culture was successfully applied. Experiments according to a 2 2 design of experiments (DOE) with star points and three center points for statistical validity allowed selecting those process conditions (Fe(II) and H 2 O 2 load) that maximized the process performance. Photo-Fenton process effectively eliminated BPA and partly degraded its by-products (residual TOC <15 %) under substoichiometric H 2 O 2 dose (100.62 mg L -1 ) and at least 4 mg L -1 Fe(II), after a 90-min treatment. All treated samples were at least partially biodegradable. The cytotoxic concentration (LD 50 ) of BPA for VERO cells was 7 mg L -1 . With small H 2 O 2 amount (15.24 mg L -1 ), only low BPA mineralization (TOC = 92 %) was attained. Toxicity was also detected to 50 % of cellular mortality even at long reaction times. However, 40.25 mg L -1 of H 2 O 2 decreased residual TOC to 70 % while cell mortality decreased down to 25 %. With more H 2 O 2 , the residual TOC decreased down to 15 % but cell mortality remained within the 20-25 % level. Photo-Fenton increased the biodegradability and reduced the toxicity of the studied sample.

Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells.

PubMed

Wei, Limin; Wang, Jianfeng; Chen, Aijie; Liu, Jia; Feng, Xiaoli; Shao, Longquan

2017-01-01

With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1 -/- BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 μg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity.

NO3-/NH4+ ratios affect nutritional homeostasis and production of Tanzania guinea grass under Cu toxicity.

PubMed

de Souza Junior, João Cardoso; Nogueirol, Roberta Corrêa; Monteiro, Francisco Antonio

2018-05-01

Nitrogen (N) can alleviate metal toxicity. However, as of yet, there have been no studies showing the efficacy of NO 3 - /NH 4 + in mitigating Cu toxicity. The objective of this study was to evaluate the Cu toxicity on the nutritional and productive attributes of Panicum maximum cv. Tanzania as well as the role of NO 3 - and NH 4 + ratios in nutritional homeostasis. The experiment was conducted using 3 × 4 factorial treatments arranged in a randomized complete block design with three replicates. The treatments were three NO 3 - /NH 4 + ratios (100/0, 70/30, and 50/50) and four Cu rates (0.3, 250, 500, and 1000 μmol L -1 ) in nutrient solution. Copper concentrations in the diagnostic leaves (DL) were highest in plants grown under 70/30 NO 3 - /NH 4 + ratios and a Cu rate of 1000 μmol L -1 . In this combination, it was observed that DL had higher concentrations of NH 4 + , greater glutamine synthetase activity, lower chlorophyll concentration (SPAD value), and lower shoot dry mass, suggesting high disorders of nutritional homeostasis. Plants receiving N in the form of NO 3 - and 1000 Cu μmol L -1 showed that DL had lower concentrations of Cu, higher concentration of chlorophyll, higher NO 3 - concentration, higher nitrate reductase activity, and higher NO 3 - accumulation in the roots, suggesting a reduction in disorders of nutritional homeostasis. The disorders on mineral uptake, N assimilation, and biomass production caused by Cu toxicity are shown to be affected by NO 3 - /NH 4 + ratios, and N supply via NO 3 - allowed for better homeostasis of the forage grass.

Glucosamine-anchored doxorubicin-loaded targeted nano-niosomes: pharmacokinetic, toxicity and pharmacodynamic evaluation.

PubMed

Pawar, Smita; Shevalkar, Ganesh; Vavia, Pradeep

2016-09-01

Efficacy of anticancer drug is limited due to non-selectivity and toxicities allied with the drug; therefore the heart of the present work is to formulate drug delivery systems targeted selectively towards cancer cells with minimal toxicity to normal cells. Targeted drug delivery system of doxorubicin (DOX)-loaded niosomes using synthesized N-lauryl glucosamine (NLG) as a targeting ligand. NLG-anchored DOX niosomes were developed using ethanol injection method. Developed niosomes had particle size <150 nm and high entrapment efficiency ∼90%. In vivo pharmacokinetics exhibited long circulating nature of targeted niosomes with improved bioavailability, which significantly reduced CL and Vd than DOX solution and non-targeted niosomes (35 fold and 2.5 fold, respectively). Tissue-distribution study and enzymatic assays revealed higher concentration of DOX solution in heart while no toxicity to major organs with developed targeted niosomes was observed. Solid skin melanoma tumor model in mice manifested the commendable targeting potential of targeted niosomes with significant reduction in tumor volume and high % survival rate without drop in body weight in comparison with DOX solution and non-targeted niosomes of DOX. The glucosamine-anchored DOX-loaded targeted niosomes showed its potential in cancer targeted drug therapy with reduced toxicity. Abbreviations ALT alanine transaminase CL clearance CPK creatinine phosphokinase DOX doxorubicin EDC.HCL ethyl carbidimide hydrochloride GLUT glucose transporter GSH glutathione S-transferase LDH lactate dehydrogenase LHRH luteinizing hormone-releasing hormone MDA malonaldehyde NHS N-hydroxy succinimide NLG N-lauryl glucosamine NTAR DoxNio non-targeted doxorubicin niosomes PBS phosphate buffer saline RGD argynyl glycyl aspartic acid SGOT serum glutamate oxaloacetate transaminase SGPT serum glutamate pyruvate transaminase SOD superoxide dismutase TAR DoxNio targeted doxorubicin niosomes Vd volume of distribution.