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

DTIC Science & Technology

2008-04-01

Chronic Sediment Toxicity Methods Jeffery Steevens, Alan Kennedy, Daniel Farrar, Cory McNemar, Mark R. Reiss, Roy K. Kropp, Jon Doi, and Todd Bridges...Research Program ERDC/EL TR-08-16 April 2008 Dredged Material Analysis Tools Performance of Acute and Chronic Sediment Toxicity Methods Jeffery...potential advan- tages and disadvantages of using chronic sediment toxicity tests with relevant benthic macroinvertebrates as part of dredged material

A toxicity assessment of 30 pharmaceuticals using Aliivibrio fischeri: a comparison of the acute effects of different formulations.

PubMed

Jacob, Raquel Sampaio; Santos, Lucilaine Valéria de Souza; de Souza, Ana Flávia Rodrigues; Lange, Liséte Celina

2016-11-01

Considerable quantities of different classes of drugs are consumed annually worldwide. These drugs, once disposed, often remain stable, even after conventional or advanced treatments. Although there have been a number of studies on the potential harm caused by drugs when released into the environment, few studies have investigated the toxicity of pharmaceutical excipients. In the present study, the acute toxicity of 30 drugs was tested to Aliivibrio fischeri. Ten different active ingredients were investigated, each in three distinct formulations: generic, similar and reference (brand drug). The aim of the study was to evaluate the harmful potential of drugs frequently sold in drugstores and to assess the contribution of excipients towards the observed acute toxicity. Within the 10 drugs evaluated, only one, dexchlorpheniramine maleate, was not toxic in any formulation. The toxicities of the three formulations were often different, even though the active ingredient has been the same. For some drugs, such as diazepam, glibenclamide, metformin, nimesulide, hydrochlorothiazide and simvastatin, only one or two of the three formulations tested were toxic to A. fischeri. These results highlight the toxicological potential of drug excipients, but not exclusively the toxicity of the active ingredients.

Classifying environmental pollutants: Part 3. External validation of the classification system.

PubMed

Verhaar, H J; Solbé, J; Speksnijder, J; van Leeuwen, C J; Hermens, J L

2000-04-01

In order to validate a classification system for the prediction of the toxic effect concentrations of organic environmental pollutants to fish, all available fish acute toxicity data were retrieved from the ECETOC database, a database of quality-evaluated aquatic toxicity measurements created and maintained by the European Centre for the Ecotoxicology and Toxicology of Chemicals. The individual chemicals for which these data were available were classified according to the rulebase under consideration and predictions of effect concentrations or ranges of possible effect concentrations were generated. These predictions were compared to the actual toxicity data retrieved from the database. The results of this comparison show that generally, the classification system provides adequate predictions of either the aquatic toxicity (class 1) or the possible range of toxicity (other classes) of organic compounds. A slight underestimation of effect concentrations occurs for some highly water soluble, reactive chemicals with low log K(ow) values. On the other end of the scale, some compounds that are classified as belonging to a relatively toxic class appear to belong to the so-called baseline toxicity compounds. For some of these, additional classification rules are proposed. Furthermore, some groups of compounds cannot be classified, although they should be amenable to predictions. For these compounds additional research as to class membership and associated prediction rules is proposed.

Sensitivity limits and EC50 values of the Vibrio fischeri test for organic micropollutants in natural and spiked extracts from sediments

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

Salizzato, M.; Bertato, V.; Pavoni, B.

1998-04-01

Chemical analyses and bioassays were used in conjunction to assess the quality of sediments of the Venice lagoon. Organic micropollutants (polycyclic aromatic hydrocarbons [PAHs] polychlorinated biphenyls [PCBs], and chlorinated pesticides) were extracted from sediment samples and analyzed by gas chromatography after fractionation into classes of compounds. The Vibrio fischeri test was used to assess the acute toxicity of sediment extracts. The test was applied to organic extracts before cleanup and to extracts purified from sulfur and fractionated into single classes of compounds. Extracts before purification were much more toxic than single fractions. In particular, sulfur was toxic to V. fischeri.more » For PAHs and PCBs the 50% effective concentration (EC50) and EC20 values were determined using natural and spiked extracts. Sensitivity limits of the method for these compounds were also estimated as was in EC50 value of elemental sulfur dissolved in ethanol. A mathematical model was used to fit the concentration-response data to a sigmoid curve.« less

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

PubMed

Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

2016-06-01

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-08-01

The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p < 0.001, LC50 in mg/L. A similar, not statistically different regression was developed for the entire data set (n = 144 chemicals, unreliable studies deleted). The FET-AFT regressions were robust for major chemical classes with suitably large data sets. Furthermore, regressions were similar to those for large groups of functional chemical categories such as pesticides, surfactants, and industrial organics. Pharmaceutical regressions (n = 8 studies only) were directionally correct. The FET-AFT relationships were not quantitatively different from acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish. Copyright © 2013 SETAC.

Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

PubMed

Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR predictions.

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

DTIC Science & Technology

2008-07-01

Chronic Sediment Toxicity Methods Jeffery Steevens, Alan Kennedy, Daniel Farrar, Cory McNemar, Mark R. Reiss, Roy K. Kropp, Jon Doi, and Todd Bridges...Environmental Research Program ERDC/EL TR-08-16 July 2008 Revised Dredged Material Analysis Tools Performance of Acute and Chronic Sediment Toxicity ...insight into the potential advan- tages and disadvantages of using chronic sediment toxicity tests with relevant benthic macroinvertebrates as part of

Status of acute systemic toxicity testing requirements and data uses by U.S. regulatory agencies.

PubMed

Strickland, Judy; Clippinger, Amy J; Brown, Jeffrey; Allen, David; Jacobs, Abigail; Matheson, Joanna; Lowit, Anna; Reinke, Emily N; Johnson, Mark S; Quinn, Michael J; Mattie, David; Fitzpatrick, Suzanne C; Ahir, Surender; Kleinstreuer, Nicole; Casey, Warren

2018-04-01

Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these data, the regulatory needs and uses for acute systemic toxicity information must first be clarified. Thus, we reviewed acute systemic toxicity testing requirements for six U.S. agencies (Consumer Product Safety Commission, Department of Defense, Department of Transportation, Environmental Protection Agency, Food and Drug Administration, Occupational Safety and Health Administration) and noted whether there is flexibility in satisfying data needs with methods that replace or reduce animal use. Understanding the current regulatory use and acceptance of non-animal data is a necessary starting point for future method development, optimization, and validation efforts. The current review will inform the development of a national strategy and roadmap for implementing non-animal approaches to assess potential hazards associated with acute exposures to industrial chemicals and medical products. The Acute Toxicity Workgroup of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), U.S. agencies, non-governmental organizations, and other stakeholders will work to execute this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

Delisting toxicity evaluation of HTH and oxone(trade name) decontaminated VX. Final report, July 1989-March 1990

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

Manthei, J.H.; Heitkamp, D.H.; Buettner, L.C.

1992-07-01

The acute percutaneous (bare skin) LD50 was determined for EA 2192 in the rabbit. Also established were the effective doses (ED50s) for the major toxic signs observed. Dermal, Department of Transportation (DOT), tests with rabbits indicated that VX/HTH decontaminated waste is a Class B poison after being aged only 24 hr following initiation of the decontamination procedure. The same reaction, when allowed to age through about 2 half-lives (28-30 days), was no longer a Class B poison and was nonhazardous by Code of Maryland Regulations (COMAR) toxicity criteria. The DOT tests with OXONE decontaminated/neutralized VX showed this solution to bemore » less than a Class B poison by all three routes of administration (rat oral, rat inhalation, and rabbit dermal) after only 24-hr aging and a nonhazardous material by COMAR toxicity criteria.... vx, Rat, Half-life, ED50, EA 2192, Rabbit, COMAR, Decontaminated/Neutralized, HTH, OXONE, LD50.« less

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

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

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

Pixberg, Caroline; Koch, Raphael; Eich, Hans Theodor, E-mail: Hans.Eich@ukmuenster.de

Purpose: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae. Materials and Methods: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Asmore » of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity. Conclusions: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior acute toxicity grade. Age seems to influence the time until maximal late toxicity but not the development of acute toxicity.« less

ACUTE TOXICITY OF SELECTED ORGANIC COMPOUNDS TO FATHEAD MINNOWS

EPA Science Inventory

Static nonrenewal laboratory bioassays were conducted with 26 organic compounds commonly used by industry. The selected compounds represented the five following chemical classes: acids, alcohols, hydrocarbons, ketones and aldehydes, and phenols. Juvenile fathead minnows (Pimephal...

Acute aquatic toxicity and biodegradation potential of biodiesel fuels

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

Haws, R.A.; Zhang, X.; Marshall, E.A.

1995-12-31

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

Residual Acute Toxicity of Some Modern Insecticides Toward Two Mirid Predators of Tomato Pests.

PubMed

Wanumen, Andrea C; Carvalho, Geraldo A; Medina, Pilar; Viñuela, Elisa; Adán, Ángeles

2016-03-31

The successful integration of chemical and biological control strategies for crop pests depends on a thorough evaluation of the effects of pesticides on the natural enemies of pests. A case-by-case review is difficult to achieve because of the many combinations of pests, natural enemies, and crops that need to be tested. Within this framework, we tested and compared seven insecticides representative of four different modes of action (MoAs) groups on closely related predators (Miridae): flubendiamide, spirotetramat, metaflumizone, and sulfoxaflor onNesidiocoris tenuisReuter and flubendiamide, spiromesifen, indoxacarb, and imidacloprid onMacrolophus basicornis(Stal). We follow the standardized methodology of the International Organization for Biological Control, a sequential testing exposure scheme. The lethal effect of each insecticide was evaluated in adults after three days of contact with treated surfaces in the laboratory, extended laboratory, and semifield tests (inert substrate, tomato leaves, and tomato plant as the treated surface, respectively). Flubendiamide, spiromesifen, and spirotetramat were classified as harmless (class 1), metaflumizone was slightly harmful (class 2) but persistent, indoxacarb was harmless (class 1), and sulfoxaflor and imidacloprid were toxic (class 4) and exhibited a long residual activity. Our results suggest similarities in the acute toxicities of insecticides from the same MoA group on related species of natural enemies. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acute oral toxicities of wildland fire control chemicals to birds

USGS Publications Warehouse

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

2009-01-01

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

Toxicity of benzotriazole and benzotriazole derivatives to three aquatic species.

PubMed

Pillard, D A; Cornell, J S; Dufresne, D L; Hernandez, M T

2001-02-01

Benzotriazole and its derivatives comprise an important class of corrosion inhibitors, typically used as trace additives in industrial chemical mixtures such as coolants, deicers, surface coatings, cutting fluids, and hydraulic fluids. Recent studies have shown that benzotriazole derivatives are a major component of aircraft deicing fluids (ADFs) responsible for toxicity to bacteria (Microtox). Our current research compared the toxicity of benzotriazole (BT), two methylbenzotriazole (MeBT) isomers, and butylbenzotriazole (BBT). Acute toxicity assays were used to model the response of three common test organisms: Microtox bacteria (Vibrio fischeri), fathead minnow (Pimephales promelas) and water flea (Ceriodaphnia dubia). The response of all the three organisms varied over two orders of magnitude among all compounds. Vibrio fischeri was more sensitive than either C. dubia or P. promelas to all the test materials, while C. dubia was less sensitive than P. promelas. The response of test organisms to unmethylated benzotriazole and 4-methylbenzotriazole was similar, whereas 5-methylbenzotriazole was more toxic than either of these two compounds. BBT was the most toxic benzotriazole derivative tested, inducing acute toxicity at a concentration of < or = 3.3 mg/l to all organisms.

Albendazole Induced Recurrent Acute Toxic Hepatitis: A Case Report.

PubMed

Bilgic, Yilmaz; Yilmaz, Cengiz; Cagin, Yasir Furkan; Atayan, Yahya; Karadag, Nese; Harputluoglu, Murat Muhsin Muhip

2017-01-01

Drug induced acute toxic hepatitis can be idiosyncratic. Albendazole, a widely used broad spectrum antiparasitic drug is generally accepted as a safe drug. It may cause asymptomatic transient liver enzyme abnormalities but acute toxic hepatitis is very rare. Case Report : Herein, we present the case of 47 year old woman with recurrent acute toxic hepatitis after a single intake of albendazole in 2010 and 2014. The patient was presented with symptoms and findings of anorexia, vomiting and jaundice. For diagnosis, other acute hepatitis etiologies were excluded. Roussel Uclaf Causality Assessment Method (RUCAM) score was calculated and found to be 10, which meant highly probable drug hepatotoxicity. Within 2 months, all pathological findings came to normal. There are a few reported cases of albendazole induced toxic hepatitis, but at adults, there is no known recurrent acute toxic hepatitis due to albendazole at this certainty according to RUCAM score. Physicians should be aware of this rare and potentially fatal adverse effect of albendazole. © Acta Gastro-Enterologica Belgica.

Evaluation of acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum L.

PubMed

da Silva, Iberê Ferreira; de Oliveira, Ruberlei Godinho; Mendes Soares, Ilsamar; da Costa Alvim, Tarso; Donizeti Ascêncio, Sérgio; de Oliveira Martins, Domingos Tabajara

2014-01-01

Piper umbellatum L., Piperaceae, is a shrub that grows up to 3m high. It is commonly known as "capeba" or "pariparoba" in Brazil. Tea prepared using the leaves of this plant is employed in the treatment of infections and inflammatory processes in different countries. Approximately 50 compounds, notably from the flavonoid, alkaloid, terpene, and sterol classes, have been isolated from the leaves of Piper umbellatum. To evaluate the acute toxicity, antibacterial activity, and mode of action of the hydroethanolic extract of Piper umbellatum leaves (HEPu). Acute toxicity of HEPu against CHO-K1 cells was evaluated using a cytotoxicity assay with Alamar Blue and that against mice was assessed by the Hippocratic test. Antibacterial activity of HEPu was tested using the broth microdilution method using a panel of clinically relevant bacteria, and the effects of HEPu on the bacterial membrane were analyzed in detail. A preliminary phytochemical analysis based on coloration/precipitation was performed according to procedure described in the literature. Secondary metabolites detected were analyzed and confirmed by thin layer chromatography (TLC), spectrophotometry, and high performance liquid chromatography (HPLC). Piper umbellatum did not appear to be toxic in the in vitro (IC50>200 µg/mL) cytotoxicity test. When administered in vivo at doses up to 2000 mg/kg p.o., HEPu did not cause any signs or symptoms of toxicity in mice. It demonstrated a good spectrum of antibacterial activity and its mode of action appeared to be associated with changes in the permeability of bacterial membranes; it led to increased entry of hydrophobic antibiotics, efflux of K(+), and nucleotide leakage. Preliminary phytochemical analysis revealed the presence of flavonoids, alkaloids, terpenes, and sterols in the extract. Spectrophotometric and HPLC analysis revealed the presence of the flavonoids rutin and quercetin. In summary, HEPu has antibacterial activity and low acute toxicity in vitro and in vivo. Its mode of action appears to be associated with changes in the permeability of the bacterial cell wall and cytoplasmic membrane, which can at least be partly attributed to the flavonoids present in the extract. © 2013 Elsevier Ireland Ltd. All rights reserved.

PREDICTION OF THE ACUTE TOXICITY OF ORGANIC COMPOUNDS TO THE FATHEAD MINNOW (PIMEPHALES PROMALAS) USING A GROUP CONTRIBUTION METHOD

EPA Science Inventory

A group contribution method has been developed to correlate the acute toxicity (96 h LC50) to the fathead minnow (Pimephales promelas) for 379 organic chemicals. Multilinear regression and computational neural networks (CNNs) were used for model building. The multilinear linear m...

Investigation of acute toxicity of fenitrothion on peppered corydoras (Corydoras paleatus) (Jenyns, 1842).

PubMed

Sarikaya, Rabia; Selvi, Mahmut; Erkoç, Figen

2004-08-01

Fenitrothion, as an organophosphothionate insecticide, is a contact insecticide and selective acaricide, also used as a vector control agent for malaria in public health programs. A 96 h LC50 value of fenitrothion, a potential toxic pollutant contaminating aquatic ecosystems, was determined on the adult peppered corydoras (Corydoras paleatus). The experiments were repeated three times. The static test method of acute toxicity test was used. Water temperature was regulated at 23 +/- 1 degrees C. In addition, behavioral changes at each fenitrothion concentration were observed for the individual fish. Data obtained from acute toxicity tests were evaluated using the Probit Analysis Statistical Method. The 96 h LC50 value for peppered corydoras was estimated as 3.51 mg/l.

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

PubMed

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

2007-04-01

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

Acute Toxicity of Fresh and Aged Residues of Pesticides to the Parasitoid Tamarixia radiata and to the HLB-Bacteria Vector Diaphorina citri.

PubMed

Beloti, V H; Alves, G R; Moral, R A; Demétrio, C G B; Yamamoto, P T

2018-06-01

One method for controlling the Asian citrus psyllid (ACP) Diaphorina citri Kuwayama, the vector of the putative causal agent of Huanglongbing, uses the parasitoid Tamarixia radiata (Waterston). However, the general intensive use of insecticides has reduced the numbers of this parasitoid. This study evaluated the effect of the residual action of 24 insecticides on T. radiata and also determined the differential toxicity of insecticides to D. citri and T. radiata, using three bioassays. In the first, when adults of the parasitoid were exposed to residues of the 24 insecticides, ten were considered short-life (class 1), six slightly persistent (class 2), five moderately persistent (class 3), and three insecticides were considered persistent (class 4), under the IOBC/WPRS classification system. The second bioassay evaluated the sublethal concentrations of the persistent insecticides (formetanate, dimethoate, spinosad). Increasing the concentrations of the insecticides increased the number that were classified as persistent. In the third bioassay, evaluation of the differential toxicity of eight insecticides to the ACP and the parasitoid showed that chlorpyrifos and bifenthrin were more harmful to T. radiata. Therefore, these two insecticides are not recommended for application at the time of parasitoid release. Cypermethrin, imidacloprid, and dimethoate caused higher mortality of D. citri and are most often recommended in IPM programs. The choice of an insecticide for the control of citrus pests must be made with care, aiming to preserve the natural enemies in the ecosystem, and thereby contribute to the success of biological control.

Reducing aquatic hazards of industrial chemicals: probabilistic assessment of sustainable molecular design guidelines.

PubMed

Connors, Kristin A; Voutchkova-Kostal, Adelina M; Kostal, Jakub; Anastas, Paul; Zimmerman, Julie B; Brooks, Bryan W

2014-08-01

Basic toxicological information is lacking for the majority of industrial chemicals. In addition to increasing empirical toxicity data through additional testing, prospective computational approaches to drug development aim to serve as a rational basis for the design of chemicals with reduced toxicity. Recent work has resulted in the derivation of a "rule of 2," wherein chemicals with an octanol-water partition coefficient (log P) less than 2 and a difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital (ΔE) greater than 9 (log P<2 and ΔE >9 eV) are predicted to be 4 to 5 times less likely to elicit acute or chronic toxicity to model aquatic organisms. The present study examines potential reduction of aquatic toxicity hazards from industrial chemicals if these 2 molecular design guidelines were employed. Probabilistic hazard assessment approaches were used to model the likelihood of encountering industrial chemicals exceeding toxicological categories of concern both with and without the rule of 2. Modeling predicted that utilization of these molecular design guidelines for log P and ΔE would appreciably decrease the number of chemicals that would be designated to be of "high" and "very high" concern for acute and chronic toxicity to standard model aquatic organisms and end points as defined by the US Environmental Protection Agency. For example, 14.5% of chemicals were categorized as having high and very high acute toxicity to the fathead minnow model, whereas only 3.3% of chemicals conforming to the design guidelines were predicted to be in these categories. Considerations of specific chemical classes (e.g., aldehydes), chemical attributes (e.g., ionization), and adverse outcome pathways in representative species (e.g., receptor-mediated responses) could be used to derive future property guidelines for broader classes of contaminants. © 2014 SETAC.

Long-term evaluation of lethal and sublethal toxicity of industrial effluents using Daphnia magna and Moina macrocopa.

PubMed

Yi, Xianliang; Kang, Sung-Wook; Jung, Jinho

2010-06-15

Acute toxicity and feeding rate inhibition of effluent from a wastewater treatment plant and its adjacent stream water on Daphnia magna and Moina macrocopa were comparatively studied. The acute toxicity of the final effluent (FE) fluctuated greatly over the sampling period from January to August 2009. Toxicity identification results of the FE in July 2009 showed that Cu originating from the Fenton's reagent was likely a key toxicant. In addition, the feeding rate of both species was still inhibited by the FEs in which acute toxicity was not observed. These findings indicate that the feeding response would be a useful tool for monitoring sublethal effects of industrial effluents. For the acute toxicity test, M. macrocopa was more sensitive than D. magna, but the opposite result was true in the case of the feeding rate inhibition. These suggest that different species have different sensitivities to toxic chemicals and to the test methods. Copyright 2010 Elsevier B.V. All rights reserved.

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients.

PubMed

De Meerleer, Gert; Vakaet, Luc; Meersschout, Sabine; Villeirs, Geert; Verbaeys, Antony; Oosterlinck, Wim; De Neve, Wilfried

2004-11-01

Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. Anatomy-based IMRT to treat prostate cancer is incorporated into our daily routine without any problem. Acute toxicity is very low. Most of the recorded symptoms decrease over time, except for GI urgency and incontinence. The incorporation of additional symptoms makes the scoring more detailed.

Severe Pulmonary Toxicity After Myeloablative Conditioning Using Total Body Irradiation: An Assessment of Risk Factors

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

Kelsey, Chris R., E-mail: kelse003@mc.duke.edu; Horwitz, Mitchell E.; Chino, Junzo P.

2011-11-01

Purpose: To assess factors associated with severe pulmonary toxicity after myeloablative conditioning using total body irradiation (TBI) followed by allogeneic stem cell transplantation. Methods and Materials: A total of 101 adult patients who underwent TBI-based myeloablative conditioning for hematologic malignancies at Duke University between 1998 and 2008 were reviewed. TBI was combined with high-dose cyclophosphamide, melphalan, fludarabine, or etoposide, depending on the underlying disease. Acute pulmonary toxicity, occurring within 90 days of transplantation, was scored using Common Terminology Criteria for Adverse Events version 3.0. Actuarial overall survival and the cumulative incidence of acute pulmonary toxicity were calculated via the Kaplan-Meiermore » method and compared using a log-rank test. A binary logistic regression analysis was performed to assess factors independently associated with acute severe pulmonary toxicity. Results: The 90-day actuarial risk of developing severe (Grade 3-5) pulmonary toxicity was 33%. Actuarial survival at 90 days was 49% in patients with severe pulmonary toxicity vs. 94% in patients without (p < 0.001). On multivariate analysis, the number of prior chemotherapy regimens was the only factor independently associated with development of severe pulmonary toxicity (odds ratio, 2.7 per regimen). Conclusions: Severe acute pulmonary toxicity is prevalent after TBI-based myeloablative conditioning regimens, occurring in approximately 33% of patients. The number of prior chemotherapy regimens appears to be an important risk factor.« less

OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

PubMed

Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

2014-08-01

The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV<30%) for most chemicals and laboratories. The reproducibility was lower (CV>30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The acute toxicity of chemically and physically dispersed crude oil to key arctic species under arctic conditions during the open water season

PubMed Central

Gardiner, William W; Word, Jack Q; Word, Jack D; Perkins, Robert A; McFarlin, Kelly M; Hester, Brian W; Word, Lucinda S; Ray, Collin M

2013-01-01

The acute toxicity of physically and chemically dispersed crude oil and the dispersant Corexit 9500 were evaluated for key Arctic species. The copepod Calanus glacialis, juvenile Arctic cod (Boreogadus saida), and larval sculpin (Myoxocephalus sp.) were tested under conditions representative of the Beaufort and Chukchi Seas during the ice-free season. The toxicity of 3 water-accommodated fractions (WAF) of Alaska North Slope crude oil was examined with spiked, declining exposures. A dispersant-only test was conducted with the copepod C. glacialis. Each preparation with oil (WAF, breaking wave WAF [BWWAF], and chemically enhanced WAF [CEWAF]) produced distinct suites of hydrocarbon constituents; the total concentrations of oil were lowest in WAF and highest in CEWAF preparations. The relative sensitivity for the different species and age classes was similar within each WAF type. Median lethal concentration values based on total petroleum hydrocarbons ranged from 1.6 mg/L to 4.0 mg/L for WAF and BWWAF treatments and from 22 mg/L to 62 mg/L for CEWAF. For Corexit 9500 exposures, median lethal concentration values ranged from 17 mg/L to 50 mg/L. The differences in the relative toxicity among the accommodated fractions indicated that the majority of petroleum hydrocarbons in the CEWAF are in less acutely toxic forms than the components that dominate the WAF or BWWAF. Further evaluation showed that the parent polycyclic aromatic hydrocarbon compounds, specifically naphthalene, were highly correlated to acute toxicity. Environ Toxicol Chem 2013;32:2284–2300. PMID:23765555

Alternative methods for the median lethal dose (LD(50)) test: the up-and-down procedure for acute oral toxicity.

PubMed

Rispin, Amy; Farrar, David; Margosches, Elizabeth; Gupta, Kailash; Stitzel, Katherine; Carr, Gregory; Greene, Michael; Meyer, William; McCall, Deborah

2002-01-01

The authors have developed an improved version of the up-and-down procedure (UDP) as one of the replacements for the traditional acute oral toxicity test formerly used by the Organisation for Economic Co-operation and Development member nations to characterize industrial chemicals, pesticides, and their mixtures. This method improves the performance of acute testing for applications that use the median lethal dose (classic LD50) test while achieving significant reductions in animal use. It uses sequential dosing, together with sophisticated computer-assisted computational methods during the execution and calculation phases of the test. Staircase design, a form of sequential test design, can be applied to acute toxicity testing with its binary experimental endpoints (yes/no outcomes). The improved UDP provides a point estimate of the LD50 and approximate confidence intervals in addition to observed toxic signs for the substance tested. It does not provide information about the dose-response curve. Computer simulation was used to test performance of the UDP without the need for additional laboratory validation.

Acute toxicity of multi-walled carbon nanotubes, sodium pentachlorophenate, and their complex on earthworm Eisenia fetida.

PubMed

Zhang, Liujun; Hu, Changwei; Wang, Weili; Ji, Funian; Cui, Yibin; Li, Mei

2014-05-01

Laboratory experiments were undertaken to relate biomarker responses to the toxicities of multi-walled carbon nanotubes (MWCNTs) and sodium pentachlorophenate (PCP-Na), both individually and combined. The acute toxicities of MWCNTs and PCP-Na on earthworm Eisenia fetida were studied through different exposure methods (filter paper contact test, immersion contact test, and artificial soil contact test). Enzyme activity and malondialdehyde (MDA) content in the earthworm E. fetida exposed to MWCNTs and PCP-Na in filter paper contact test, both individually and under combined exposure, were determined. After exposure, PCP-Na induced observable acute toxicity while the MWCNTs induced slight toxicity. Interestingly the earthworms exposed to the mixture of MWCNTs and PCP-Na demonstrated different expression of enzymatic biomarkers from those exposed to MWCNTs or PCP-Na alone. Our results indicated that the toxicity of PCP-Na on E. fetida may be alleviated by the appearance of MWCNTs for all exposure methods except for immersion contact test. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Changes in the metabolome may serve as peripheral biomarkers of CNS toxicity.

EPA Science Inventory

Since our observation that an acute exposure to different classes of pesticides resulted in different changes in plasma metabolomics markers, a study of the metabolome has become of high interest for identifying markers of neurotoxicity. A Biocrates AbsoluteIDQTM p180 platform wa...

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 ...

Small Bowel Dose Parameters Predicting Grade ≥3 Acute Toxicity in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation: An Independent Validation Study Comparing Peritoneal Space Versus Small Bowel Loop Contouring Techniques

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

Banerjee, Robyn, E-mail: robynbanerjee@gmail.com; Chakraborty, Santam; Nygren, Ian

Purpose: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. Methods and Materials: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Results: Grade ≥3more » small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. Conclusion: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity.« less

Immuno-therapy of Acute Radiation Syndromes : Extracorporeal Immuno-Lympho-Plasmo-Sorption.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Methods Results Summary and conclusions Introduction: Existing Medical Management of the Acute Radiation Syndromes (ARS) does not include methods of specific immunotherapy and active detoxication. Though the Acute Radiation Syndromes were defined as an acute toxic poisonous with development of pathological processes: Systemic Inflammatory Response Syndrome (SIRS), Toxic Multiple Organ Injury (TMOI), Toxic Multiple Organ Dysfunction Syndrome(TMODS), Toxic Multiple Organ Failure (TMOF). Radiation Toxins of SRD Group play an important role as the trigger mechanisms in development of the ARS clinical symptoms. Methods: Immuno-Lympho-Plasmo-Sorption is a type of Immuno-therapy which includes prin-ciples of immunochromato-graphy, plasmopheresis, and hemodialysis. Specific Antiradiation Antitoxic Antibodies are the active pharmacological agents of immunotherapy . Antiradia-tion Antitoxic Antibodies bind selectively to Radiation Neurotoxins, Cytotoxins, Hematotox-ins and neutralize their toxic activity. We have developed the highly sensitive method and system for extracorporeal-immune-lypmh-plasmo-sorption with antigen-specific IgG which is clinically important for treatment of the toxic and immunologic phases of the ARS. The method of extracorporeal-immune-lypmh-plasmo-sorption includes Antiradiation Antitoxic Antibodies (AAA) immobilized on microporous polymeric membranes with a pore size that is capable to provide diffusion of blood-lymph plasma. Plasma of blood or lymph of irradiated mammals contains Radiation Toxins (RT) that have toxic and antigenic properties. Radiation Toxins are Antigen-specific to Antitoxic blocking antibodies (Immunoglobulin G). Plasma diffuses through membranes with immobilized AAA and AA-antibodies bind to the polysaccharide chain of tox-ins molecules and complexes of AAA-RT that are captured on membrane surfaces. RT were removed from plasma. Re-transfusion of plasma of blood and lymph had been provided. We show a statistical significant reduction in postradiation lethality.

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.

Comparison of bulk sediment and sediment elutriate toxicity testing methods

EPA Science Inventory

Elutriate bioassays are among numerous methods that exist for assessing the potential toxicity of sediments in aquatic systems. In this study, interlaboratory results were compared from 96-hour Ceriodaphnia dubia and Pimephales promelas static-renewal acute toxicity tests conduct...

ECOSAR model performance with a large test set of industrial chemicals.

PubMed

Reuschenbach, Peter; Silvani, Maurizio; Dammann, Martina; Warnecke, Dietmar; Knacker, Thomas

2008-05-01

The widely used ECOSAR computer programme for QSAR prediction of chemical toxicity towards aquatic organisms was evaluated by using large data sets of industrial chemicals with varying molecular structures. Experimentally derived toxicity data covering acute effects on fish, Daphnia and green algae growth inhibition of in total more than 1,000 randomly selected substances were compared to the prediction results of the ECOSAR programme in order (1) to assess the capability of ECOSAR to correctly classify the chemicals into defined classes of aquatic toxicity according to rules of EU regulation and (2) to determine the number of correct predictions within tolerance factors from 2 to 1,000. Regarding ecotoxicity classification, 65% (fish), 52% (Daphnia) and 49% (algae) of the substances were correctly predicted into the classes "not harmful", "harmful", "toxic" and "very toxic". At all trophic levels about 20% of the chemicals were underestimated in their toxicity. The class of "not harmful" substances (experimental LC/EC(50)>100 mg l(-1)) represents nearly half of the whole data set. The percentages for correct predictions of toxic effects on fish, Daphnia and algae growth inhibition were 69%, 64% and 60%, respectively, when a tolerance factor of 10 was allowed. Focussing on those experimental results which were verified by analytically measured concentrations, the predictability for Daphnia and algae toxicity was improved by approximately three percentage points, whereas for fish no improvement was determined. The calculated correlation coefficients demonstrated poor correlation when the complete data set was taken, but showed good results for some of the ECOSAR chemical classes. The results are discussed in the context of literature data on the performance of ECOSAR and other QSAR models.

Comparative acute toxicity of gallium(III), antimony(III), indium(III), cadmium(II), and copper(II) on freshwater swamp shrimp (Macrobrachium nipponense).

PubMed

Yang, Jen-Lee

2014-04-01

Acute toxicity testing were carried out the freshwater swamp shrimp, Macrobrachium nipponense, as the model animal for the semiconductor applied metals (gallium, antimony, indium, cadmium, and copper) to evaluate if the species is an suitable experimental animal of pollution in aquatic ecosystem. The static renewal test method of acute lethal concentrations determination was used, and water temperature was maintained at 24.0 ± 0.5°C. Data of individual metal obtained from acute toxicity tests were determined using probit analysis method. The median lethal concentration (96-h LC50) of gallium, antimony, indium, cadmium, and copper for M. nipponense were estimated as 2.7742, 1.9626, 6.8938, 0.0539, and 0.0313 mg/L, respectively. Comparing the toxicity tolerance of M. nipponense with other species which exposed to these metals, it is obviously that the M. nipponense is more sensitive than that of various other aquatic animals.

Reducing the incidence of acute pesticide poisoning by educating farmers on integrated pest management in South India.

PubMed

Mancini, Francesca; Jiggins, Janice L S; O'Malley, Michael

2009-01-01

Sixty-five farmers reported on pesticide use and the signs and symptoms of acute pesticide poisoning when using two different plant protection strategies: in 2003 using chemical controls and in 2004 using an approach to Integrated Pest Management (IPM) based on an ecological analysis of the field conditions. Exposure to organophosphates was confirmed as a serious risk factor for occupational poisoning. The adoption of IPM reduced the use of pesticides and halved the incidence of acute pesticide poisoning. Overall, the pesticide use spectrum shifted towards lower WHO Hazard Classes. A reduction of adverse health effects was attained through a reduction in exposure to toxic pesticides and behavioural changes. Given that other strategies to reduce the rate of acute poisoning have proven ineffective, interventions aiming to minimize pesticide poisoning in India and in other developing countries with similar rural conditions should focus on restricting the use of highly toxic compounds and educating farmers on IPM.

Oral and intramuscular toxicity of inorganic and organic mercury chloride to growing quail

USGS Publications Warehouse

Hill, E.F.; Soares, J.H.

1987-01-01

The lethal toxicity of inorganic (HgCl2) and organic (CH3HgCl) mercury chloride was compared for Coturnix (Japanese quail, Coturnix japonica) of different ages from hatch through adulthood by single-dose acute oral and intramuscular injections and by a 5-d dietary trial. Sublethal mercury toxicity was studied by evaluation of plasma and brain cholinesterase activity. CH3HgCl was more toxic than HgCl2 in all tests at each age tested. LD50s consistently increased over the first 4 wk for both acute methods and both mercurials and then stabilized. The striking difference between single-dose acute and 5-d dietary tests was that CH3HgCl averaged about twice as toxic as HgCl2 by both acute methods, compared to 100 times as toxic by the dietary method. For example, at 2 wk of age, the oral LD50s for CH3HgCl and HgCl2 were 18 and 42 mg/kg and the dietary LC50s were 47 and 5086 ppm. When birds were fed HgCl2 and developed clinical signs of intoxication, they could recover once treatment was withdrawn; however, on CH3HgCl, clinical signs often commenced after treatment was withdrawn, and then actually intensified for several days and culminated in death.

An interlaboratory comparison of sediment elutriate preparation and toxicity test methods

EPA Science Inventory

Elutriate bioassays are among numerous methods that exist for assessing the potential toxicity of sediments in aquatic systems. In this study, interlaboratory results were compared from 96-hour Ceriodaphnia dubia and Pimephales promelas static-renewal acute toxicity tests conduct...

Prediction of pesticide acute toxicity using two-dimensional chemical descriptors and target species classification

EPA Science Inventory

Previous modelling of the median lethal dose (oral rat LD50) has indicated that local class-based models yield better correlations than global models. We evaluated the hypothesis that dividing the dataset by pesticidal mechanisms would improve prediction accuracy. A linear discri...

MULTIMEDIA CHEMICAL ANALYSIS PLAN FOR CHILDREN'S AGGREGATE EXPOSURE FIELD STUDIES IN NORTH CAROLINA AND OHIO

EPA Science Inventory

The samples collected in the CTEPP North Carolina and Ohio field campaigns were analyzed for a suite of organic chemicals in various compound classes, chosen because of their possible carcinogenicity, acute or chronic toxicity, or potential for endocrine system disruption. The...

Characterization of stuA mutants in the mycotoxigenic maize pathogen Fusarium verticillioides

USDA-ARS?s Scientific Manuscript database

Fusarium verticillioides is a major pathogen of maize, causing root, stalk and ear rots and seedling blight. It also produces fumonisin mycotoxins. Ingestion of fumonisin-contaminated corn causes acute toxicity in livestock and is a potential carcinogen to humans. StuA, an APSES protein class transc...

Acute bioassays and hazard evaluation of representative contaminants detected in Great Lakes fish

USGS Publications Warehouse

Passino, Dora R. May; Smith, Stephen B.

1987-01-01

We have provided a hazard ranking for 19 classes of compounds representing many of the nearly 500 organic compounds identified by gas chromatography-mass spectrometry in lake trout (Salvelinus namaycush) and walleye (Stizostedion vitreum vitreum) from the Great Lakes and Lake St. Clair. We initially made a provisional hazard ranking based on available published and unpublished information on aquatic toxicity, bioaccumulation, occurrence and sources. Acute toxicity tests with Daphnia pulex at 17A°C in reconstituted hard water were performed with 30 compounds representative of the 19 classes that were highest in the provisional ranking. The resulting toxicity data, along with information on the compounds' occurrence in Great Lakes fish and their sources, were ranked and weighted and then used in calculating the revised hazard ranking. The 10 most hazardous classes, in descending order, are as follows (values shown are mean 48-h EC50s, in μ/ml): arene halides (e.g., polychlorinated biphenyls, DDT), 0.0011; phthalate esters, 0.133; chlorinated camphenes (toxaphene), 0.0082; polyaromatic hydrocarbons (PAHs; e.g., dimethylnaphthalene) and reduced derivatives, 1.01; chlorinated fused polycyclics (e.g., trans-nonachlor), 0.022; nitrogen-containing compounds (e.g., O-methylhydroxyl-amine), 1.35; alkyl halides (e.g., (bromomethyl)cyclohexene), 10.1; cyclic alkanes (e.g., cyclododecane), 20.9; silicon-containing compounds (e.g., dimethyldiethoxy silane), 1.25; and heterocyclic nitrogen compounds (e.g., nicotine), 2.48. We recommend that chronic bioassays be conducted with fish and invertebrates to determine the sublethal effects of the following classes of compounds, for which few toxicity data are available: PAHs, heterocyclic nitrogen compounds, other nitrogen-containing compounds, alkyl halides, cyclic alkanes and silicon-containing compounds. Information from these types of studies will aid researchers in determining the possible causal role these contaminants play in the decline and reproductive impairment of Great Lakes fish.

Development of a Complete Life Cycle Sediment Toxicity Test for the Sheepshead Minnow (Cyprinodon variegatus)

EPA Science Inventory

Existing sediment toxicity test methods are limited to acute and chronic exposure of invertebrates and acute exposure of vertebrates, with limited guidance on the chronic exposure of vertebrates, specifically fishes. A series of life stage-specific studies were conducted to dete...

DO TIE LABORATORY BASED METHODS REALLY REFLECT FIELD CONDITIONS

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 ...

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...

Probabilistic risk assessment of cotton pyrethroids: I. Distributional analyses of laboratory aquatic toxicity data.

PubMed

Solomon, K R; Giddings, J M; Maund, S J

2001-03-01

This is the first in a series of five papers that assess the risk of the cotton pyrethroids in aquatic ecosystems in a series of steps ranging from the analysis of effects data through modeling exposures in the landscape. Pyrethroid insecticides used on cotton have the potential to contaminate aquatic systems. The objectives of this study were to develop probabilistic estimates of toxicity distributions, to compare these among the pyrethroids, and to evaluate cypermethrin as a representative pyrethroid for the purposes of a class risk assessment of the pyrethroids. The distribution of cypermethrin acute toxicity data gave 10th centile values of 10 ng/L for all organisms, 6.4 ng/L for arthropods, and 380 ng/L for vertebrates. For bifenthrin, cyfluthrin, lambda-cyhalothrin, and deltamethrin, the 10th centile values for all organisms were 15, 12, 10, and 9 ng/L, respectively, indicating similar or somewhat lower toxicity than cypermethrin. For tralomethrin and fenpropathrin, the 10th centiles were <310 and 240 ng/L, respectively. The distribution of permethrin toxicity to all organisms, arthropods, and vertebrates gave 10th centiles of 180, 76, and 1600 ng/L, respectively, whereas those for fenvalerate were 37, 8, and 150 ng/L. With the exception of tralomethrin, the distributions of acute toxicity values had similar slopes, suggesting that the variation of sensitivity in a range of aquatic nontarget species is similar. The pyrethroids have different recommended field rates of application that are related to their efficacy, and the relationship between field rate and 10th centiles showed a trend. These results support the use of cypermethrin as a reasonable worst-case surrogate for the other pyrethroids for the purposes of risk assessment of pyrethroids as a class.

Is there a role for progesterone in the management of acute organophosphate poisoning during pregnancy?

PubMed

Jafarzadeh, Mostafa; Nasrabadi, Zeynab Nasri; Sheikhazadi, Ardeshir; Abbaspour, Abdollah; Vasigh, Shayesteh; Yousefinejad, Vahid; Marashi, Sayed Mahdi

2013-06-01

Organophosphates are commonly used pesticides and cause about one million unintentional and 2 million suicidal exposures with up to 300,000 fatalities every year around the world. Toxicity of organophosphates is due to inhibition cholinesterase activity and prolonging the effects of acetylcholine in the receptor site. Clinical features of organophosphate poisoning are defecation, urination, miosis, bronchorrhea, emesis, lacrimation and salivation. Spontaneous abortion reported some when in pregnant patients. Intravenous administration of benzodiazepines, atropine and pralidoxime is the formal treatment of this toxicity. Atropine and pralidoxime have been assigned to pregnancy class C by the FDA and should be recommended for use in pregnant women clinically suffer organophosphate poisoning. Benzodiazepines have been assigned to pregnancy class D and should be avoided during pregnancy. Clinical experiments suggest transplacental transfer of organophosphates is possible, and fetal sensitivity is probable, but a single acute overdose most likely don't make any physical deformities, therefore termination of pregnancy is not imperative. Nonetheless, no definite strategy focused on maintaining pregnancy. Here we propose an idea that in any female case of acute organophosphate poisoning in childbearing range of age, maternal serum Beta-HCG should be tested for pregnancy and prophylactic progesterone should be used in pregnant cases of organophosphate poisoning. Copyright © 2013 Elsevier Ltd. All rights reserved.

DO TIE LABORATORY BASED ASSESSMENT METHODS REALLY PREDICT FIELD EFFECTS?

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...

Dose-additivity modeling for acute and repeated exposure to a mixture of N-methycarbamate Pesticides

EPA Science Inventory

The toxicity of N-methylcarbamate pesticides is attributed to the reversible inhibition of cholinesterase (ChE) enzymes in the central and peripheral nervous system. The inhibition of ChE following a single exposure to this class of pesticides has been modeled using a dose-additi...

Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

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

Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca; Fortin, Andre; Wang, Chang Shu

2012-03-15

Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, andmore » the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting could help tailoring therapies to reduce toxicities among patients treated with RT for HNC.« less

Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

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

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; EMR3738, Université Lyon 1, Lyon; Decullier, Evelyne

Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Eventsmore » version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.« less

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

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

Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.

2008-06-01

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

Acute toxicity and its dosimetric correlates for high-risk prostate cancer treated with moderately hypofractionated radiotherapy

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

Arunsingh, Moses; Mallick, Indranil, E-mail: imallick@gmail.com; Prasath, Sriram

Aims: To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer. Methods: A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65 Gy/25 Fr/5 weeks (n = 18), or 60 Gy/20 Fr/4 weeks (n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified. Results: The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2more » genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2 Gy equivalent doses (EQD2) to the rectum and bladder (α/β = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V{sub EQD2-60} {sub Gy} (13.2 vs 9.9 cc, p = 0.007) and V{sub EQD2-50} {sub Gy} (20.6 vs 15.4 cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher V{sub EQD2-70} {sub Gy} (30.4 vs 18.4 cc, p = 0.001) and V{sub EQD2-65} {sub Gy} (44.0 vs 28.8 cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for V{sub EQD2-60} {sub Gy} was 9.7 cc and for V{sub EQD2-50} {sub Gy} was 15.9 cc. For grade 2 GU symptoms, the threshold values were 23.6 cc for V{sub EQD2-70} {sub Gy} and 38.1 cc for V{sub EQD2-65} {sub Gy}. Conclusions: Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.« less

User’s Guide for T.E.S.T. (version 4.2) (Toxicity Estimation Software Tool) A Program to Estimate Toxicity from Molecular Structure

EPA Science Inventory

The user's guide describes the methods used by TEST to predict toxicity and physical properties (including the new mode of action based method used to predict acute aquatic toxicity). It describes all of the experimental data sets included in the tool. It gives the prediction res...

Cumulative toxicity of neonicotinoid insecticide mixtures to Chironomus dilutus under acute exposure scenarios.

PubMed

Maloney, Erin M; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

2017-11-01

Extensive agricultural use of neonicotinoid insecticide products has resulted in the presence of neonicotinoid mixtures in surface waters worldwide. Although many aquatic insect species are known to be sensitive to neonicotinoids, the impact of neonicotinoid mixtures is poorly understood. In the present study, the cumulative toxicities of binary and ternary mixtures of select neonicotinoids (imidacloprid, clothianidin, and thiamethoxam) were characterized under acute (96-h) exposure scenarios using the larval midge Chironomus dilutus as a representative aquatic insect species. Using the MIXTOX approach, predictive parametric models were fitted and statistically compared with observed toxicity in subsequent mixture tests. Single-compound toxicity tests yielded median lethal concentration (LC50) values of 4.63, 5.93, and 55.34 μg/L for imidacloprid, clothianidin, and thiamethoxam, respectively. Because of the similar modes of action of neonicotinoids, concentration-additive cumulative mixture toxicity was the predicted model. However, we found that imidacloprid-clothianidin mixtures demonstrated response-additive dose-level-dependent synergism, clothianidin-thiamethoxam mixtures demonstrated concentration-additive synergism, and imidacloprid-thiamethoxam mixtures demonstrated response-additive dose-ratio-dependent synergism, with toxicity shifting from antagonism to synergism as the relative concentration of thiamethoxam increased. Imidacloprid-clothianidin-thiamethoxam ternary mixtures demonstrated response-additive synergism. These results indicate that, under acute exposure scenarios, the toxicity of neonicotinoid mixtures to C. dilutus cannot be predicted using the common assumption of additive joint activity. Indeed, the overarching trend of synergistic deviation emphasizes the need for further research into the ecotoxicological effects of neonicotinoid insecticide mixtures in field settings, the development of better toxicity models for neonicotinoid mixture exposures, and the consideration of mixture effects when setting water quality guidelines for this class of pesticides. Environ Toxicol Chem 2017;36:3091-3101. © 2017 SETAC. © 2017 SETAC.

A phase III randomized, placebo-controlled, double-blind study of misoprostol rectal suppositories to prevent acute radiation proctitis in patients with prostate cancer

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

Hille, Andrea; Schmidberger, Heinz; Hermann, Robert M.

2005-12-01

Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo andmore » the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding.« less

Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience

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

Gold, Douglas G.; Miller, Robert C.; Petersen, Ivy A.

2007-02-01

Purpose: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. Methods and Materials: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. Results: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grademore » 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. Conclusions: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.« less

Assessing deep and shallow learning methods for quantitative prediction of acute chemical toxicity.

PubMed

Liu, Ruifeng; Madore, Michael; Glover, Kyle P; Feasel, Michael G; Wallqvist, Anders

2018-05-02

Animal-based methods for assessing chemical toxicity are struggling to meet testing demands. In silico approaches, including machine-learning methods, are promising alternatives. Recently, deep neural networks (DNNs) were evaluated and reported to outperform other machine-learning methods for quantitative structure-activity relationship modeling of molecular properties. However, most of the reported performance evaluations relied on global performance metrics, such as the root mean squared error (RMSE) between the predicted and experimental values of all samples, without considering the impact of sample distribution across the activity spectrum. Here, we carried out an in-depth analysis of DNN performance for quantitative prediction of acute chemical toxicity using several datasets. We found that the overall performance of DNN models on datasets of up to 30,000 compounds was similar to that of random forest (RF) models, as measured by the RMSE and correlation coefficients between the predicted and experimental results. However, our detailed analyses demonstrated that global performance metrics are inappropriate for datasets with a highly uneven sample distribution, because they show a strong bias for the most populous compounds along the toxicity spectrum. For highly toxic compounds, DNN and RF models trained on all samples performed much worse than the global performance metrics indicated. Surprisingly, our variable nearest neighbor method, which utilizes only structurally similar compounds to make predictions, performed reasonably well, suggesting that information of close near neighbors in the training sets is a key determinant of acute toxicity predictions.

GHS additivity formula: A true replacement method for acute systemic toxicity testing of agrochemical formulations.

PubMed

Corvaro, M; Gehen, S; Andrews, K; Chatfield, R; Arasti, C; Mehta, J

2016-12-01

Acute systemic (oral, dermal, inhalation) toxicity testing of agrochemical formulations (end-use products) is mainly needed for Classification and Labelling (C&L) and definition of personal protection equipment (PPE). A retrospective analysis of 225 formulations with available in vivo data showed that: A) LD 50 /LC 50 values were above limit doses in <20.2% via oral route but only in <1% and <2.4% of cases via dermal and inhalation route, respectively; B) for each formulation the acute oral toxicity is always equal or greater than the Acute Toxicity Estimate (ATE) via the other two routes; C) the GHS (Global Harmonised System) computational method based on ATE, currently of limited acceptance, has very high accuracy and specificity for prediction of agrochemical mixture toxicity according to the internationally established classification thresholds. By integrating this evidence, an exposure- and data-based waiving strategy is proposed to determine classification and adequate PPE and to ensure only triggered animal testing is used. Safety characterisation above 2000 mg/kg body weight or 1.0 mg/L air should not be recommended, based on the agrochemical exposure scenarios. The global implementation of these tools would allow a remarkable reduction (up to 95%) in in vivo testing, often inducing lethality and/or severe toxicity, for agrochemical formulations. Copyright © 2016. Published by Elsevier Inc.

Progress Towards the Development of a Fathead Minnow Embryo Test and Comparison to the Zebrafish Embryo Test for Assessing Acute Fish Toxicity

EPA Science Inventory

The Zebrafish Embryo Test (ZFET) for acute fish toxicity is a well developed method nearing adoption as an OECD Test Guideline. Early drafts of the test guideline (TG) envisioned a suite of potential test species to be covered including zebrafish, fathead minnow, Japanese Medaka...

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.

Acute toxicity and effects analysis of endosulfan sulfate to freshwater fish species.

PubMed

Carriger, John F; Hoang, Tham C; Rand, Gary M; Gardinali, Piero R; Castro, Joffre

2011-02-01

Endosulfan sulfate is a persistent environmental metabolite of endosulfan, an organochlorine insecticide-acaricide presently registered by the United States Environmental Protection Agency. There is, however, limited acute fish toxicity data for endosulfan sulfate. This study determines the acute toxicity (LC₅₀s and LC₁₀s) of endosulfan sulfate to three inland Florida native fish species (mosquitofish [Gambusia affinis]; least killifish [Heterandria formosa]; and sailfin mollies [Poecilia latipinna]) as well as fathead minnows (Pimephales promelas). Ninety-six-h acute toxicity tests were conducted with each fish species under flow-through conditions. For all of the above-mentioned fish species, 96-h LC₅₀ estimates ranged from 2.1 to 3.5 μg/L endosulfan sulfate. The 96-h LC₁₀ estimates ranged from 0.8 to 2.1 μg/L endosulfan sulfate. Of all of the fish tested, the least killifish appeared to be the most sensitive to endosulfan sulfate exposure. The above-mentioned data were combined with previous acute toxicity data for endosulfan sulfate and freshwater fish for an effects analysis. The effects analysis estimated hazardous concentrations expected to exceed 5, 10, and 50% of the fish species' acute LC₅₀ or LC₁₀ values (HC₅, HC₁₀, and HC₅₀). The endosulfan sulfate freshwater-fish acute tests were also compared with the available freshwater-fish acute toxicity data for technical endosulfan. Technical endosulfan is a mixture of α- and β-endosulfan. The LC₅₀s had a wider range for technical endosulfan, and their distribution produced a lower HC₁₀ than for endosulfan sulfate. The number of freshwater-fish LC₅₀s for endosulfan sulfate is much smaller than the number available for technical endosulfan, reflecting priorities in examining the toxicity of the parent compounds of pesticides. The toxicity test results and effects analyses provided acute effect values for endosulfan sulfate and freshwater fish that might be applied in future screening level ecologic risk assessments. The effects analyses also discussed several deficiencies in conventional methods for setting water-quality criteria and determining ecologic effects from acute toxicity tests.

A Study on the D. magna and V. fischeri Toxicity Relationship of Industrial Wastewater from Korea

NASA Astrophysics Data System (ADS)

Pyo, S.; Lee, S.; Chun Sang, H.; Park, T. J.; Kim, M. S.

2015-12-01

It is well known that high concentration of TDS (total dissolved solid) in industrial effluent gives rise to the toxicity to the Daphnia magna toxicity test. D. magna is vulnerable to relatively low TDS concentration showing the 24-hr EC50 of Salinity 0.6% (as the sea salt concentration). Recently, standard mandatory toxicity testing using Daphnia magna has been used to monitor industrial effluent toxicity according to Korea standard method (Acute Toxicity Test Method of the Daphnia magna Straus (Cladocera, Crustacea), ES 04704. 1a) under regulation. Since only one acute toxicity testing is applied in the present, we are trying to introduce microbial battery for more complete toxicity assessment. In this study, the acute toxicities between daphnids and microbes were compared. The results of D. magna and Vibrio fischeri toxicity test from 165 industrial wastewater effluents showed high positive correlation. In addition, the possibility of predicting daphnia toxicity from the bacterial toxicity data amounts to 92.6% if we consider salinity effect (>5ppt) together. From this study, we found that the V. fischeri toxicity test is a powerful battery tool to assess the industrial wastewater toxicity. Here, we suggest that luminescent bacteria toxicity test be useful not only for complete toxicity assessment which can't be obtained by daphnia toxicity testing only but also for the reduction cost, time, and labor in the Korean society. Keywords : D. magna, V. fischeri, Industrial waste water, battery test Acknowledgement This research was supported by a grant (15IFIP-B089908-02) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes

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

Kotecha, Rupesh; Djemil, Toufik; Tendulkar, Rahul D.

Purpose: To report the short-term clinical outcomes and acute and late treatment-related genitourinary (GU) and gastrointestinal (GI) toxicities in patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT). Methods and Materials: Between 2011 and 2014, 24 patients with prostate cancer were treated with SBRT to the prostate gland and proximal seminal vesicles. A high-dose avoidance zone (HDAZ) was created by a 3-mm expansion around the rectum, urethra, and bladder. Patients were treated to a minimum dose of 36.25 Gy in 5 fractions, with a simultaneous dose escalation to a dose of 50 Gy to the targetmore » volume away from the HDAZ. Acute and late GU and GI toxicity outcomes were measured according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 4. Results: The median follow-up was 25 months (range, 18-45 months). Nine patients (38%) experienced an acute grade 2 GU toxicity, which was medically managed, and no patients experienced an acute grade 2 GI toxicity. Two patients (8%) experienced late grade 2 GU toxicity, and 2 patients (8%) experienced late grade 2 GI toxicity. No acute or late grade ≥3 GU or GI toxicities were observed. The 24-month prostate-specific antigen relapse-free survival outcome for all patients was 95.8% (95% confidence interval 75.6%-99.4%), and both biochemical failures occurred in patients with high-risk disease. All patients are currently alive at the time of this analysis and continue to be followed. Conclusions: A heterogeneous prostate SBRT planning technique with differential treatment volumes (low dose: 36.25 Gy; and high dose: 50 Gy) with an HDAZ provides a safe method of dose escalation. Favorable rates of biochemical control and acceptably low rates of acute and long-term GU and GI toxicity can be achieved in patients with intermediate- and high-risk prostate cancer treated with SBRT.« less

Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: failure of another indirect cytotoxicity analysis.

PubMed

Coco, Rosa M; Srivastava, Girish K; Andrés-Iglesias, Cristina; Medina, Jesús; Rull, Fernando; Fernandez-Vega-Gonzalez, Alvaro; Fernandez-Bueno, Ivan; Dueñas, Antonio; Pastor, Jose C

2018-03-29

To report new information related to acute retinal toxicity of Bio Octane Plus, a mixture of 90% perfluorooctane (PFO) and 10% perfluorohexyloctane. This retrospective, descriptive case series reports the occurrence of acute retinal toxicity after vitreoretinal surgery in which Bio Octane Plus (batch number 1605148) was used as an endotamponade. Cytotoxicity biocompatibility tests and chemical analyses by Fourier-transformed infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) of the presumed toxic product were performed. Four patients presented with acute severe visual loss after uneventful ocular surgery assisted by Bio Octane Plus (batch number 1605148) as endotamponade. Patients experienced extensive retinal vascular occlusion leading to retinal and optic nerve atrophy. The viability of ARPE-19 cells directly exposed to the suspect batch for 30 min was 0%. The agarose overlay method used by the manufacturer according to European Union regulations and International Organization for Standardization (ISO) International Standards failed to detect toxicity. FTIR spectroscopy showed small differences between the non-toxic and toxic batches. GC-MS analysis showed the presence of bromotributyl stannane (whose toxicity was demonstrated in the dose-response curve) only in the toxic batch of Bio Octane Plus. This is the third report of retinotoxicity due to PFO in 4 years. The clinical profiles may be missed as they resemble other postsurgical complications; therefore, more cases worldwide could have gone unreported. Protocols to determine cytotoxicity of intraocular medical devices and approved by the ISO International Standards based on indirect methods have failed and should be revised to ensure safety. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An assessment of agricultural pesticide use in Iran, 2012-2014.

PubMed

Morteza, Zaim; Mousavi, Seyed Behzad; Baghestani, Mohammad Ali; Aitio, Antero

2017-01-01

This is the first published assessment on agricultural pesticide use in Iran with the aim to identify pesticide products with a potential of causing acute or chronic hazard to human health. It also establishes a baseline for future comparisons and for trend assessments. The amounts of imported technical materials for formulation by local manufacturers as well as imported final product formulations were extracted from the registration data of the Plant Protection Organization of Iran in 2012-2014. The hazard indicators used were acute oral toxicity and chronic toxicity. For the latter, carcinogenicity, mutagenicity, and adverse effects on reproduction or development (CMR toxicity), and low Acceptable Daily Intake (ADI) were used. The comparative potential of the active ingredients of concern in terms of chronic toxicity was assessed using the average annual volume of their estimated use divided by their respective ADI, called chronic hazard potential (CHP) in the present text. The contribution of individual pesticides in different use categories to the total CHP of the user category, was also calculated, using the average annual volume of the active ingredients of all pesticides used during the period 2012-2014. On average about 14,000 tonnes of agriculture pesticides, expressed in active ingredients (AI), were annually used in Iran. Herbicides constituted the largest volume (43%), followed by insecticides and acaricides (37%) and fungicides (19%). 0.1% and 47% of the formulated products met the criteria of WHO Class Ib (highly hazardous) and Class II (moderately hazardous) products respectively. Aluminium phosphide and magnesium phosphide were identified as products of primary concern and chlorpyrifos, diazinon and paraquat as products of secondary concern, in terms of their acute human health hazard. No compound in carcinogenicity category 1A or 1B or germ cell mutagenicity/reproduction toxicity category 1A was identified. Six compounds (diazinon, chlorpyrifos, dichlorvos, metam sodium, paraquat and dimethoate) were identified as products with chronic hazard potential based on a low ADI. The assessment identified and prioritized agriculture pesticide used in Iran in terms of their acute and chronic hazard to human health for re-registration scheme recently established by PPO and for risk mitigation. It also set priority for research into development of alternative products and practices to minimize pesticide risks. Chronic hazard potential - amount of use adjusted with toxicity may serve as a useful point of reference for trend analysis also in the use of less hazardous agricultural pesticide products.

Identification of novel uncertainty factors and thresholds of toxicological concern for health hazard and risk assessment: Application to cleaning product ingredients.

PubMed

Wang, Zhen; Scott, W Casan; Williams, E Spencer; Ciarlo, Michael; DeLeo, Paul C; Brooks, Bryan W

2018-04-01

Uncertainty factors (UFs) are commonly used during hazard and risk assessments to address uncertainties, including extrapolations among mammals and experimental durations. In risk assessment, default values are routinely used for interspecies extrapolation and interindividual variability. Whether default UFs are sufficient for various chemical uses or specific chemical classes remains understudied, particularly for ingredients in cleaning products. Therefore, we examined publicly available acute median lethal dose (LD50), and reproductive and developmental no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) values for the rat model (oral). We employed probabilistic chemical toxicity distributions to identify likelihoods of encountering acute, subacute, subchronic and chronic toxicity thresholds for specific chemical categories and ingredients in cleaning products. We subsequently identified thresholds of toxicological concern (TTC) and then various UFs for: 1) acute (LD50s)-to-chronic (reproductive/developmental NOAELs) ratios (ACRs), 2) exposure duration extrapolations (e.g., subchronic-to-chronic; reproductive/developmental), and 3) LOAEL-to-NOAEL ratios considering subacute/acute developmental responses. These ratios (95% CIs) were calculated from pairwise threshold levels using Monte Carlo simulations to identify UFs for all ingredients in cleaning products. Based on data availability, chemical category-specific UFs were also identified for aliphatic acids and salts, aliphatic alcohols, inorganic acids and salts, and alkyl sulfates. In a number of cases, derived UFs were smaller than default values (e.g., 10) employed by regulatory agencies; however, larger UFs were occasionally identified. Such UFs could be used by assessors instead of relying on default values. These approaches for identifying mammalian TTCs and diverse UFs represent robust alternatives to application of default values for ingredients in cleaning products and other chemical classes. Findings can also support chemical substitutions during alternatives assessment, and data dossier development (e.g., read across), identification of TTCs, and screening-level hazard and risk assessment when toxicity data is unavailable for specific chemicals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of toxicity and estrogenicity of the landfill-concentrated leachate during advanced oxidation treatment: chemical analyses and bioanalytical tools.

PubMed

Wang, Guifang; Lu, Gang; Zhao, Jiandi; Yin, Pinghe; Zhao, Ling

2016-08-01

Landfill-concentrated leachate from membrane separation processes is a potential pollution source for the surroundings. In this study, the toxicity and estrogenicity potentials of concentrated leachate prior to and during UV-Fenton and Fenton treatments were assessed by a combination of chemical (di (2-ethylhexyl) phthalate and dibutyl phthalate were chosen as targets) and biological (Daphnia magna, Chlorella vulgaris, and E-screen assay) analyses. Removal efficiencies of measured di (2-ethylhexyl) phthalate and dibutyl phthalate were more than 97 % after treatment with the two methods. Biological tests showed acute toxicity effects on D. magna tests in untreated concentrated leachate samples, whereas acute toxicity on C. vulgaris tests was not observed. Both treatment methods were found to be efficient in reducing acute toxicity effects on D. magna tests. The E-screen test showed concentrated leachate had significant estrogenicity, UV-Fenton and Fenton treatment, especially the former, were effective methods for reducing estrogenicity of concentrated leachate. The EEQchem (estradiol equivalent concentration) of all samples could only explain 0.218-5.31 % range of the EEQbio. These results showed that UV-Fenton reagent could be considered as a suitable method for treatment of concentrated leachate, and the importance of the application of an integrated (biological + chemical) analytical approach for a comprehensive evaluation of treatment suitability.

Toxins produced in cyanobacterial water blooms – toxicity and risks

PubMed Central

Bláha, Luděk; Babica, Pavel; Maršálek, Blahoslav

2009-01-01

Cyanobacterial blooms in freshwaters represent a major ecological and human health problem worldwide. This paper briefly summarizes information on major cyanobacterial toxins (hepatotoxins, neurotoxins etc.) with special attention to microcystins-cyclic heptapeptides with high acute and chronic toxicities. Besides discussion of human health risks, microcystin ecotoxicology and consequent ecological risks are also highlighted. Although significant research attention has been paid to microcystins, cyanobacteria produce a wide range of currently unknown toxins, which will require research attention. Further research should also address possible additive, synergistic or antagonistic effects among different classes of cyanobacterial metabolites, as well as interactions with other toxic stressors such as metals or persistent organic pollutants. PMID:21217843

A combined evaluation of the characteristics and acute toxicity of antibiotic wastewater.

PubMed

Yu, Xin; Zuo, Jiane; Li, Ruixia; Gan, Lili; Li, Zaixing; Zhang, Fei

2014-08-01

The conventional parameters and acute toxicities of antibiotic wastewater collected from each treatment unit of an antibiotic wastewater treatment plant have been investigated. The investigation of the conventional parameters indicated that the antibiotic wastewater treatment plant performed well under the significant fluctuation in influent water quality. The results of acute toxicity indicated that the toxicity of antibiotic wastewater could be reduced by 94.3 percent on average after treatment. However, treated antibiotic effluents were still toxic to Vibrio fischeri. The toxicity of antibiotic production wastewater could be attributed to the joint effects of toxic compound mixtures in wastewater. Moreover, aerobic biological treatment processes, including sequencing batch reactor (SBR) and aerobic biofilm reactor, played the most important role in reducing toxicity by 92.4 percent. Pearson׳s correlation coefficients revealed that toxicity had a strong and positive linear correlation with organic substances, nitrogenous compounds, S(2-), volatile phenol, cyanide, As, Zn, Cd, Ni and Fe. Ammonia nitrogen (NH4(+)) was the greatest contributor to toxicity according to the stepwise regression method. The multiple regression model was a good fit for [TU50-15 min] as a function of [NH₄(+)] with the determination coefficient of 0.981. Copyright © 2014 Elsevier Inc. All rights reserved.

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

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

Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu; Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

2011-12-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy.more » Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible, with acceptable acute and chronic toxicity.« less

Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

PubMed

Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

2006-10-01

An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC(50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

PubMed

Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

2014-08-01

Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acute toxicity value extrapolation with fish and aquatic invertebrates

USGS Publications Warehouse

Buckler, Denny R.; Mayer, Foster L.; Ellersieck, Mark R.; Asfaw, Amha

2005-01-01

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

The second case of a young man with L-arginine-induced acute pancreatitis.

PubMed

Binet, Quentin; Dufour, Inès; Agneessens, Emmanuel; Debongnie, Jean-Claude; Aouattah, Tarik; Covas, Angélique; Coche, Jean-Charles; De Koninck, Xavier

2018-04-21

Dietary supplementation of arginine has been used by numerous world-class athletes and professional bodybuilders over the past 30 years. L-Arginine indeed enhances muscular power and general performance via maintaining ATP level. However, L-arginine is also known to induce acute pancreatitis in murine models. We report the case of young man presenting with upper abdominal pain and increased serum lipase levels. Contrast-enhanced computed tomography confirms a mild acute pancreatitis. Common etiologies have been ruled out and toxicological anamnestic screening reveals the intake of protein powder. This is, to the best of our knowledge, the second case in human of arginine-induced acute pancreatitis. This case report suggests that every patient presenting with acute pancreatitis without obvious etiology should be evaluated for the intake of toxics other than alcohol, including L-arginine.

Acute toxicity of heavy metals for benthic epiphytic foraminifera Pararotalia spinigera (Le Calvez) and influence of seaweed-derived DOC

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

Bresler, V.; Yanko, V.

1995-10-01

The acute toxicity of cadmium, copper, and mercury to the benthic epiphytic foraminiferan Pararotalia spinigera (Le Calvez) was investigated using seven different vital cytophysiological and cytochemical methods. The ability to enzymatically hydrolyze the fluorogenic substrates fluorescein diacetate or fluorescein dibutyrate was the most sensitive method of LC50 value determination. The LC50 (24-h) values for cadmium, copper, and mercury determined by this assay with fluorescein diacetate was 0.56, 1.4, and 0.07 {micro}M, respectively. The content of seaweed-derived dissolved organic carbon (DOC), measured by absorbance at 436 nm, produced a dramatic increase of LC50 values for the heavy metals in a dose-dependentmore » manner. ``Intact`` epiphytic foraminifera attached to seaweeds are less sensitive to acute toxicity of cadmium, copper, and mercury than are ``detached`` foraminifera.« less

In vitro antibacterial activity and acute toxicity studies of aqueous-methanol extract of Sida rhombifolia Linn. (Malvaceae)

PubMed Central

2010-01-01

Background Many bacteria among the Enterobacteria family are involved in infectious diseases and diarrhoea. Most of these bacteria become resistant to the most commonly used synthetic drugs in Cameroon. Natural substances seem to be an alternative to this problem. Thus the aim of this research was to investigate the in vitro antibacterial activity of the methanol and aqueous-methanol extracts of Sida rhombifolia Linn (Malvaceae) against seven pathogenic bacteria involved in diarrhoea. Acute toxicity of the most active extract was determined and major bioactive components were screened. Methods The agar disc diffusion and the agar dilution method were used for the determination of inhibition diameters and the Minimum Inhibitory Concentration (MICs) respectively. The acute toxicity study was performed according WHO protocol. Results The aqueous-methanol extract (1v:4v) was the most active with diameters of inhibition zones ranging from 8.7 - 23.6 mm, however at 200 μg/dic this activity was relatively weak compared to gentamycin. The MICs of the aqueous-methanol extract (1v:4v) varied from 49.40 to 78.30 μg/ml. Salmonella dysenteriae was the most sensitive (49.40 μg/ml). For the acute toxicity study, no deaths of rats were recorded. However, significant increase of some biochemical parameters such as aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatinine (CRT) were found. The phytochemical analysis of the aqueous methanol extract indicated the presence of tannins, polyphenols, alkaloids, glycosides, flavonoids and saponins Conclusion The results showed that the aqueous-methanol extract of S. rhombifolia exhibited moderate antibacterial activity. Some toxic effects were found when rats received more than 8 g/kg bw of extract. Antibacterial; Enterobacteria; Acute toxicity; Phytochemical analysis PMID:20663208

Acute and Cumulative Effects of Unmodified 50-nm Nano-ZnO on Mice.

PubMed

Kong, Tao; Zhang, Shu-Hui; Zhang, Ji-Liang; Hao, Xue-Qin; Yang, Fan; Zhang, Cai; Yang, Zi-Jun; Zhang, Meng-Yu; Wang, Jie

2018-01-02

Nanometer zinc oxide (nano-ZnO) is widely used in diverse industrial and agricultural fields. Due to the extensive contact humans have with these particles, it is crucial to understand the potential effects that nano-ZnO have on human health. Currently, information related to the toxicity and mechanisms of nano-ZnO is limited. The aim of the present study was to investigate acute and cumulative toxic effects of 50-nm unmodified ZnO in mice. This investigation will seek to establish median lethal dose (LD50), a cumulative coefficient, and target organs. The acute and cumulative toxicity was investigated by Karber's method and via a dose-increasing method, respectively. During the experiment, clinical signs, mortality, body weights, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. The LD50 was 5177-mg/kg·bw; the 95% confidence limits for the LD50 were 5116-5238-mg/kg·bw. It could be concluded that the liver, kidney, lung, and gastrointestinal tract were target organs for the 50-nm nano-ZnO acute oral treatment. The cumulative coefficient (K) was 1.9 which indicated that the cumulative toxicity was apparent. The results also indicated that the liver, kidney, lung, and pancrea were target organs for 50-nm nano-ZnO cumulative oral exposure and might be target organs for subchronic and chronic toxicity of oral administered 50-nm ZnO.

In Vitro Methods To Measure Toxicity Of Chemicals

DTIC Science & Technology

2004-12-01

industrial compounds for toxicity will require high-throughput in vitro assays with which to select candidate compounds for more intensive animal...for estimating the starting dose for the rat oral acute toxicity test, thus reducing and refining the use of animals in the toxicological

Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents

PubMed Central

Fedorova, Elena V.; Buryakina, Anna V.; Zakharov, Alexey V.; Filimonov, Dmitry A.; Lagunin, Alexey A.; Poroikov, Vladimir V.

2014-01-01

Based on the data about structure and antidiabetic activity of twenty seven vanadium and zinc coordination complexes collected from literature we developed QSAR models using the GUSAR program. These QSAR models were applied to 10 novel vanadium coordination complexes designed in silico in order to predict their hypoglycemic action. The five most promising substances with predicted potent hypoglycemic action were selected for chemical synthesis and pharmacological evaluation. The selected coordination vanadium complexes were synthesized and tested in vitro and in vivo for their hypoglycemic activities and acute rat toxicity. Estimation of acute rat toxicity of these five vanadium complexes was performed using a freely available web-resource (http://way2drug.com/GUSAR/acutoxpredict.html). It has shown that the selected compounds belong to the class of moderate toxic pharmaceutical agents, according to the scale of Hodge and Sterner. Comparison with the predicted data has demonstrated a reasonable correspondence between the experimental and predicted values of hypoglycemic activity and toxicity. Bis{tert-butyl[amino(imino)methyl]carbamato}oxovanadium (IV) and sodium(2,2′-Bipyridyl)oxo-diperoxovanadate(V) octahydrate were identified as the most potent hypoglycemic agents among the synthesized compounds. PMID:25057899

Ecotoxicological effects of carbofuran and oxidised multiwalled carbon nanotubes on the freshwater fish Nile tilapia: nanotubes enhance pesticide ecotoxicity.

PubMed

Campos-Garcia, Janaína; Martinez, Diego Stéfani T; Alves, Oswaldo L; Leonardo, Antônio Fernando Gervásio; Barbieri, Edison

2015-01-01

The interactions of carbon nanotubes with pesticides, such as carbofuran, classical contaminants (e.g., pesticides, polyaromatic hydrocarbons, heavy metals, and dyes) and emerging contaminants, including endocrine disruptors, are critical components of the environmental risks of this important class of carbon-based nanomaterials. In this work, we studied the modulation of acute carbofuran toxicity to the freshwater fish Nile tilapia (Oreochromis niloticus) by nitric acid treated multiwalled carbon nanotubes, termed HNO3-MWCNT. Nitric acid oxidation is a common chemical method employed for the purification, functionalisation and aqueous dispersion of carbon nanotubes. HNO3-MWCNT were not toxic to Nile tilapia at concentrations ranging from 0.1 to 3.0 mg/L for exposure times of up to 96 h. After 24, 48, 72 and 96 h, the LC50 values of carbofuran were 4.0, 3.2, 3.0 and 2.4 mg/mL, respectively. To evaluate the influence of carbofuran-nanotube interactions on ecotoxicity, we exposed the Nile tilapia to different concentrations of carbofuran mixed together with a non-toxic concentration of HNO3-MWCNT (1.0 mg/L). After 24, 48, 72, and 96 h of exposure, the LC50 values of carbofuran plus nanotubes were 3.7, 1.6, 0.7 and 0.5 mg/L, respectively. These results demonstrate that HNO3-MWCNT potentiate the acute toxicity of carbofuran, leading to a more than five-fold increase in the LC50 values. Furthermore, the exposure of Nile tilapia to carbofuran plus nanotubes led to decreases in both oxygen consumption and swimming capacity compared to the control. These findings indicate that carbon nanotubes could act as pesticide carriers affecting fish survival, metabolism and behaviour. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of hyperforin on the morphology of internal organs and biochemical parameters, in experimental model in mice.

PubMed

Negreş, Simona; Scutari, Corina; Ionică, Floriana Elvira; Gonciar, Veaceslav; Velescu, Bruno Ştefan; Şeremet, Oana Cristina; Zanfirescu, Anca; Zbârcea, Cristina Elena; Ştefănescu, Emil; Ciobotaru, Emilia; ChiriŢă, Cornel

2016-01-01

Hyperforin (HY) is used to treat depression and skin irritation and has been shown a number of pharmacological activities. The literature does no cite data on changes that may occur in the body after HY intake (ethylene diammonium salt - EDS) in long-term administration. From this point of view, the present work is a key to determining the pharmacotoxicological profile of the HY-EDS, in long-term administration. In present research, the influence of toxic doses of HY-EDS was investigated on the biochemical serum parameters and the histopathological changes in internal organs on the experimental mice model. For acute toxicity determination, the HY-EDS was tested in doses of 2000-5000 mg÷kg, administered once per day orally. For subacute toxicity, the HY-EDS was tested in three groups of mice, in doses of 50, 75 and 100 mg÷kg÷day, administered once daily, for 28 consecutive days. As concern acute toxicity, a lethal effect has not occurred at any of the two tested doses and HY-EDS was classified as Class V toxic: median lethal dose (LD50) >5000 mg÷kg, p.o. After 14 days of follow-up in acute toxicity, the experimental results showed a statistically significant increase of aspartate transaminase (AST) and alanine transaminase (ALT), compared to the control group. There were no changes in creatinine and serum glucose compared to the control group. After the administration of repeated doses, it was observed an increase of serum transaminases and alkaline phosphatase. Histological examination revealed that the liver injuries were in an initial stage, making them reversible in case of HY-EDS treatment discontinuation. There was no evidence of kidney damage to any of the doses of HY-EDS.

Predicting acute aquatic toxicity of structurally diverse chemicals in fish using artificial intelligence approaches.

PubMed

Singh, Kunwar P; Gupta, Shikha; Rai, Premanjali

2013-09-01

The research aims to develop global modeling tools capable of categorizing structurally diverse chemicals in various toxicity classes according to the EEC and European Community directives, and to predict their acute toxicity in fathead minnow using set of selected molecular descriptors. Accordingly, artificial intelligence approach based classification and regression models, such as probabilistic neural networks (PNN), generalized regression neural networks (GRNN), multilayer perceptron neural network (MLPN), radial basis function neural network (RBFN), support vector machines (SVM), gene expression programming (GEP), and decision tree (DT) were constructed using the experimental toxicity data. Diversity and non-linearity in the chemicals' data were tested using the Tanimoto similarity index and Brock-Dechert-Scheinkman statistics. Predictive and generalization abilities of various models constructed here were compared using several statistical parameters. PNN and GRNN models performed relatively better than MLPN, RBFN, SVM, GEP, and DT. Both in two and four category classifications, PNN yielded a considerably high accuracy of classification in training (95.85 percent and 90.07 percent) and validation data (91.30 percent and 86.96 percent), respectively. GRNN rendered a high correlation between the measured and model predicted -log LC50 values both for the training (0.929) and validation (0.910) data and low prediction errors (RMSE) of 0.52 and 0.49 for two sets. Efficiency of the selected PNN and GRNN models in predicting acute toxicity of new chemicals was adequately validated using external datasets of different fish species (fathead minnow, bluegill, trout, and guppy). The PNN and GRNN models showed good predictive and generalization abilities and can be used as tools for predicting toxicities of structurally diverse chemical compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?

PubMed

Van Cott, Andrew; Hastings, Charles E; Landsiedel, Robert; Kolle, Susanne; Stinchcombe, Stefan

2018-02-01

In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formulations tested for inhalation toxicity and 31 formulations tested for dermal toxicity. The GHS additivity formula was applied to each of these formulations and compared with the experimental in vivo result. In the acute oral assay, the GHS additivity formula misclassified 110 formulations using the GHS classification criteria (48% accuracy) and 119 formulations using the USEPA classification criteria (43% accuracy). With acute inhalation, the GHS additivity formula misclassified 50 formulations using the GHS classification criteria (61% accuracy) and 34 formulations using the USEPA classification criteria (73% accuracy). For acute dermal toxicity, the GHS additivity formula misclassified 16 formulations using the GHS classification criteria (48% accuracy) and 20 formulations using the USEPA classification criteria (36% accuracy). This data indicates the acute systemic toxicity of many formulations is not the sum of the ingredients' toxicity (additivity); but rather, ingredients in a formulation can interact to result in lower or higher toxicity than predicted by the GHS additivity formula. Copyright © 2018 Elsevier Inc. All rights reserved.

Linear solvation energy relationships for toxicity of selected organic chemicals to Daphnia pulex and Daphnia magna

USGS Publications Warehouse

Passino, Dora R.M.; Hickey, James P.; Frank, Anthony M.

1988-01-01

In the Laurentian Great Lakes, more than 300 contaminants have been identified in fish, other biota, water, and sediment. Current hazard assessment of these chemicals by the National Fisheries Research Center-Great Lakes is based on their toxicity, occurrence in the environment, and source. Although scientists at the Center have tested over 70 chemicals with the crustacean Daphnia pulex, the number of experimental data needed to screen the huge array of chemicals in the Great Lakes exceeds the practical capabilities of conducting bioassays. This limitation can be partly circumvented, however, by using mathematical models based on quantitative structure-activity relationships (QSAR) to provide rapid, inexpensive estimates of toxicity. Many properties of chemicals, including toxicity, bioaccumulation and water solubility are well correlated and can be predicted by equations of the generalized linear solvation energy relationships (LSER). The equation we used to model solute toxicity is Toxicity = constant + mVI/100 + s (π* + dδ) + bβm + aαm where VI = intrinsic (Van der Waals) molar volume; π* = molecular dipolarity/polarizability; δ = polarizability 'correction term'; βm = solute hydrogen bond acceptor basicity; and αm = solute hydrogen bond donor acidity. The subscript m designates solute monomer values for α and β. We applied the LSER model to 48-h acute toxicity data (measured as immobilization) for six classes of chemicals detected in Great Lakes fish. The following regression was obtained for Daphnia pulex (concentration = μM): log EC50 = 4.86 - 4.35 VI/100; N = 38, r2 = 0.867, sd = 0.403 We also used the LSER modeling approach to analyze to a large published data set of 24-h acute toxicity for Daphnia magna; the following regression resulted, for eight classes of compounds (concentration = mM): log EC50 = 3.88 - 4.52 VI/100 - 1.62 π* + 1.66 βm - 0.916 αm; N = 62, r2 = 0.859, sd = 0.375 In addition we developed computer software that identifies chemical structures, estimates the LSER parameters, and predicts toxicity. The LSER models promise to be effective in differentiating between reactive and nonreactive toxicity behavior where other models have failed. Contaminants with reactive behavior are generally the most toxic and rank highest in hazard assessment of environmental chemicals.

Acute oral toxicity: variability, reliability, relevance and interspecies comparison of rodent LD50 data from literature surveyed for the ACuteTox project.

PubMed

Hoffmann, Sebastian; Kinsner-Ovaskainen, Agnieszka; Prieto, Pilar; Mangelsdorf, Inge; Bieler, Christian; Cole, Thomas

2010-12-01

The ACuteTox project has aimed to optimise and prevalidate an in vitro testing strategy for predicting human acute toxicity. Ninety-seven reference substances were selected and an in vivo acute toxicity database was compiled. Comprehensive statistical analyses of the in vivo LD50 data to evaluate variability and reliability, interspecies correlation, predictive capacities with regard to EU and GHS toxicity categories, and deduction of performance criteria for in vitro methods is presented. For the majority of substances variability among rodent data followed a log normal distribution where good reproducibility was found. Rat and mouse interspecies comparison of LD50 studies by ordinary regression showed high correlation, with coefficients of determination, ranging between 0.8 and 0.9. Substance specific differences were only significant for warfarin and cycloheximide. No correlation of compound LD50 range with presumed study quality rank (by assigning Klimisch reliability scores) was found. Modelling based on LD50 variability showed that with at least 90% probability ∼54% of the substances would fall into only one GHS category and ∼44% would fall within two adjacent categories. These results could form the basis for deriving a predictive capacity that should be expected from alternative approaches to the conventional in vivo acute oral toxicity test. Copyright © 2010 Elsevier Inc. All rights reserved.

A Predictive Model for Toxicity Effects Assessment of Biotransformed Hepatic Drugs Using Iterative Sampling Method.

PubMed

Tharwat, Alaa; Moemen, Yasmine S; Hassanien, Aboul Ella

2016-12-09

Measuring toxicity is one of the main steps in drug development. Hence, there is a high demand for computational models to predict the toxicity effects of the potential drugs. In this study, we used a dataset, which consists of four toxicity effects:mutagenic, tumorigenic, irritant and reproductive effects. The proposed model consists of three phases. In the first phase, rough set-based methods are used to select the most discriminative features for reducing the classification time and improving the classification performance. Due to the imbalanced class distribution, in the second phase, different sampling methods such as Random Under-Sampling, Random Over-Sampling and Synthetic Minority Oversampling Technique are used to solve the problem of imbalanced datasets. ITerative Sampling (ITS) method is proposed to avoid the limitations of those methods. ITS method has two steps. The first step (sampling step) iteratively modifies the prior distribution of the minority and majority classes. In the second step, a data cleaning method is used to remove the overlapping that is produced from the first step. In the third phase, Bagging classifier is used to classify an unknown drug into toxic or non-toxic. The experimental results proved that the proposed model performed well in classifying the unknown samples according to all toxic effects in the imbalanced datasets.

Dose to organs at risk in the upper abdomen in patients treated with extended fields by helical tomotherapy: a dosimetric and clinical preliminary study

PubMed Central

2013-01-01

Background The aim of this work was to determine the technical feasibility and safety of extended-field radiotherapy (EF), performed by Helical TomoTherapy, in patients with positive pelvic and/or para-aortic nodes. Dosimetric data were collected and acute and sub-acute toxicities of the upper abdominal organs at risk (OAR) were evaluated. Methods Twenty-nine patients suitable for EF irradiation for local disease and/or nodal disease in the pelvic or para-aortic area were treated. The prescription dose was 50.4/54 Gy (1.7-1.8 Gy/fraction) for prophylactic lymph nodes (N-) and 60–70.5 Gy (2–2.35 Gy/fraction) for clinically evident gross disease (N+). Modulation factor (MF), pitch and field width (FW) were chosen to optimize dose distribution and treatment duration. Dose values of PTVs and OAR were analysed. The length of the treatment field, the N + and N- volumes, and treatment duration were reported. To evaluate the safety of treatment, haematological, hepatic, renal and pancreatic functions were assessed before, during and after treatment. The median follow-up time was 17.6 months (range: 6–22 months). Results The treatment was well tolerated and all patients but one completed treatment without interruption. Four of the 29 patients experienced G3 haematological acute toxicity (13.8%), but no patient experienced sub-acute grade G3 toxicity. Ten patients experienced G1 and three G2 acute gastrointestinal toxicity (nausea). No sub-acute gastrointestinal or renal toxicity was observed. Only one (3.7%) patient had a persistent slight increase of pancreatic enzymes and two (7.4%) patients a slight increase of hepatic enzymes six months after radiotherapy (G1 toxicity). Conclusions With our treatment design and dose regimen, we found that EF treatment by TomoTherapy could be safely and effectively delivered with minimal acute and sub-acute toxicities in the upper abdomen area. PMID:24160769

A Critical Review of Mode of Action (MOA) Assignment ...

EPA Pesticide Factsheets

There are various structure-based classification schemes to categorize chemicals based on mode of action (MOA) which have been applied for both eco and human health toxicology. With increasing calls to assess thousands of chemicals, some of which have little available information other than structure, clear understanding how each of these MOA schemes was devised, what information they are based on, and the limitations of each approach is critical. Several groups are developing low-tier methods to more easily classify or assess chemicals, using approaches such as the ecological threshold of concern (eco-TTC) and chemical-activity. Evaluation of these approaches and determination of their domain of applicability is partly dependent on the MOA classification that is used. The most commonly used MOA classification schemes for ecotoxicology include Verhaar and Russom (included in ASTER), both of which are used to predict acute aquatic toxicity MOA. Verhaar is a QSAR-based system that classifies chemicals into one of 4 classes, with a 5th class specified for those chemicals that are not classified in the other 4. ASTER/Russom includes 8 classifications: narcotics (3 groups), oxidative phosphorylation uncouplers, respiratory inhibitors, electrophiles/proelectrophiles, AChE inhibitors, or CNS seizure agents. Other methodologies include TEST (Toxicity Estimation Software Tool), a computational chemistry-based application that allows prediction to one of 5 broad MOA

New Rotifer Bioassays for Aquatic Toxicology

DTIC Science & Technology

1991-07-01

Acute toxicity tests using rotifers. II. A freshwater test with Brachionus rubens. Aquatic Toxicology. 14: 81-92. Snell, T. W., B. D. Moffat, C. Janssen...24 hours with a sensitivity comparable to that of other aquatic invertebrates. 1. Standard Freshwater Medium Preparation: Carefully add 96 mg NaHCO3,60...rubens. Aquatic Toxicology. 14: 81-92. US Environmental Protection Agency 1985. Methods for measuring the acute toxicity of effluents to freshwater

Influence of pesticide regulation on acute poisoning deaths in Sri Lanka.

PubMed Central

Roberts, Darren M.; Karunarathna, Ayanthi; Buckley, Nick A.; Manuweera, Gamini; Sheriff, M. H. Rezvi; Eddleston, Michael

2003-01-01

OBJECTIVES: To assess in a developing Asian country the impact of pesticide regulation on the number of deaths from poisoning. These regulations, which were implemented in Sri Lanka from the 1970s, aimed to reduce the number of deaths - the majority from self-poisoning - by limiting the availability and use of highly toxic pesticides. METHODS: Information on legislative changes was obtained from the Ministry of Agriculture, national and district hospital admission data were obtained from the Sri Lanka Health Statistics Unit, and individual details of deaths by pesticide poisoning were obtained from a manual review of patients' notes and intensive care unit records in Anuradhapura. FINDINGS: Between 1986 and 2000, the total national number of admissions due to poisoning doubled, and admissions due to pesticide poisoning increased by more than 50%. At the same time, the case fatality proportion (CFP) fell for total poisonings and for poisonings due to pesticides. In 1991_92, 72% of pesticide-induced deaths in Anuradhapura were caused by organophosphorus (OP) and carbamate pesticides - in particular, the WHO class I OPs monocrotophos and methamidophos. From 1991, the import of these pesticides was reduced gradually until they were banned for routine use in January 1995, with a corresponding fall in deaths. Unfortunately, their place in agricultural practice was taken by the WHO class II organochlorine endosulfan, which led to a rise in deaths from status epilepticus - from one in 1994 to 50 in 1998. Endosulfan was banned in 1998, and over the following three years the number of endosulfan deaths fell to three. However, at the end of the decade, the number of deaths from pesticides was at a similar level to that of 1991, with WHO class II OPs causing the most deaths. Although these drugs are less toxic than class I OPs, the management of class II OPs remains difficult because they are, nevertheless, still highly toxic, and their toxicity is exacerbated by the paucity of available facilities. CONCLUSION: The fall in CFP amidst a rising incidence of self-poisoning suggests that Sri Lanka's programmes of pesticide regulation were beneficial. However, a closer inspection of pesticide-induced deaths in one hospital revealed switching to other highly toxic pesticides, as one was banned and replaced in agricultural practice by another. Future regulation must predict this switching and bear in mind the ease of treatment of replacement pesticides. Furthermore, such regulations must be implemented alongside other strategies, such as integrated pest management, to reduce the overall pesticide availability for self-harm. PMID:14758405

Comparative acute toxicity of leachates from plastic products made of polypropylene, polyethylene, PVC, acrylonitrile-butadiene-styrene, and epoxy to Daphnia magna.

PubMed

Lithner, Delilah; Nordensvan, Ildikó; Dave, Göran

2012-06-01

The large global production of plastics and their presence everywhere in the society and the environment create a need for assessing chemical hazards and risks associated with plastic products. The aims of this study were to determine and compare the toxicity of leachates from plastic products made of five plastics types and to identify the class of compounds that is causing the toxicity. Selected plastic types were those with the largest global annual production, that is, polypropylene, polyethylene, and polyvinyl chloride (PVC), or those composed of hazardous monomers (e.g., PVC, acrylonitrile-butadiene-styrene [ABS], and epoxy). Altogether 26 plastic products were leached in deionized water (3 days at 50°C), and the water phases were tested for acute toxicity to Daphnia magna. Initial Toxicity Identification Evaluations (C18 filtration and EDTA addition) were performed on six leachates. For eleven leachates (42%) 48-h EC50s (i.e the concentration that causes effect in 50 percent of the test organisms) were below the highest test concentration, 250 g plastic/L. All leachates from plasticized PVC (5/5) and epoxy (5/5) products were toxic (48-h EC50s ranging from 2 to 235 g plastic/L). None of the leachates from polypropylene (5/5), ABS (5/5), and rigid PVC (1/1) products showed toxicity, but one of the five tested HDPE leachates was toxic (48-h EC50 17-24 g plastic/L). Toxicity Identification Evaluations indicated that mainly hydrophobic organics were causing the toxicity and that metals were the main cause for one leachate (metal release was also confirmed by chemical analysis). Toxic chemicals leached even during the short-term leaching in water, mainly from plasticized PVC and epoxy products.

INTERLABORATORY COMPARISON OF A REDUCED VOLUME MARINE SEDIMENT TOXICITY TEST METHOD USING AMPHIPOD AMPELISCA ABDITA

EPA Science Inventory

The U.S. Environmental Protection Agency has standardized methods for performing acute marine amphipod sediment toxicity tests. A test design reducing sediment volume from 200 to 50 ml and overlying water from 600 to 150 ml was recently proposed. An interlaboratory comparison wa...

Postoperative Intensity-Modulated Arc Therapy for Cervical and Endometrial Cancer: A Prospective Report on Toxicity

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

Vandecasteele, Katrien, E-mail: Katrien.Vandecasteele@uzgent.be; Tummers, Philippe; Makar, Amin

2012-10-01

Purpose: To report on toxicity after postoperative intensity-modulated arc therapy (IMAT) for cervical (CC) and endometrial cancer (EC). Methods and Materials: Twenty-four CC and 41 EC patients were treated with postoperative IMAT. If indicated, para-aortic lymph node irradiation (preventive or when affected, PALN) and/or concomitant cisplatin (40 mg/m Superscript-Two , weekly) was administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation-related toxicity was assessed prospectively. The effect of concomitant cisplatin and PALN irradiation was evaluated. Results: Regarding acute toxicity (n = 65), Grademore » 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and 3 (12%) hematologic toxicity (n = 41) occurred only in CC patients. Seventeen percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin toxicity, respectively. Adding cisplatin led to an increase in Grade >2 nausea (57% vs. 9%; p = 0.01), Grade 2 nocturia (24% vs. 4%; p = 0.03), Grade {>=}2 hematologic toxicity (38% vs. nil, p = 0.003), Grade {>=}2 leukopenia (33% vs. nil, p = 0.009), and a strong trend toward more fatigue (14% vs. 2%; p = 0.05). Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31% vs. 4%, p = 0.008) and a strong trend toward more Grade >2 nausea (44% vs. 18%; p = 0.052). Regarding late toxicity (n = 45), no Grade 3 or 4 late toxicity occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN irradiation increased late toxicity rates. Conclusions: Postoperative IMAT for EC or CC is associated with low acute and late toxicity. Concomitant chemotherapy and PALN irradiation influences acute but not late toxicity.« less

Toxicity Studies on Antiradiation Agents.

DTIC Science & Technology

1979-03-01

Mice 193-403 WI 2823 Acute Oral and IP Toxicity in Guinea Pigs 193-404 WR 2823 14-Day IV Toxicity in Rats 193-405 WI 2823 Acute IV Toxicity in Dogs ...193-406 W 2823 14-Day Subacute IV Toxicity in Dogs 193-407 WI 2721 28-Day Oral Toxicity in Monkeys 193-408 WI 2529 Acute Oral Toxicity in Mice 193-409... Dogs 193-415 WI 149, 024 Acute IV Toxicity in Monkeys 193-416 WI 149, 024 2-Week IV Toxicity in Dogs 193-417 WI 149, 024 2-Week Toxicity in Monkeys 193

Diagnostic accuracy of ultrasonic histogram features to evaluate radiation toxicity of the parotid glands: a clinical study of xerostomia following head-and-neck cancer radiotherapy.

PubMed

Yang, Xiaofeng; Tridandapani, Srini; Beitler, Jonathan J; Yu, David S; Chen, Zhengjia; Kim, Sungjin; Bruner, Deborah W; Curran, Walter J; Liu, Tian

2014-10-01

To investigate the diagnostic accuracy of ultrasound histogram features in the quantitative assessment of radiation-induced parotid gland injury and to identify potential imaging biomarkers for radiation-induced xerostomia (dry mouth)-the most common and debilitating side effect after head-and-neck radiotherapy (RT). Thirty-four patients, who have developed xerostomia after RT for head-and-neck cancer, were enrolled. Radiation-induced xerostomia was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity scale. Ultrasound scans were performed on each patient's parotids bilaterally. The 34 patients were stratified into the acute-toxicity groups (16 patients, ≤ 3 months after treatment) and the late-toxicity group (18 patients, > 3 months after treatment). A separate control group of 13 healthy volunteers underwent similar ultrasound scans of their parotid glands. Six sonographic features were derived from the echo-intensity histograms to assess acute and late toxicity of the parotid glands. The quantitative assessments were compared to a radiologist's clinical evaluations. The diagnostic accuracy of these ultrasonic histogram features was evaluated with the receiver operating characteristic (ROC) curve. With an area under the ROC curve greater than 0.90, several histogram features demonstrated excellent diagnostic accuracy for evaluation of acute and late toxicity of parotid glands. Significant differences (P < .05) in all six sonographic features were demonstrated between the control, acute-toxicity, and late-toxicity groups. However, subjective radiologic evaluation cannot distinguish between acute and late toxicity of parotid glands. We demonstrated that ultrasound histogram features could be used to measure acute and late toxicity of the parotid glands after head-and-neck cancer RT, which may be developed into a low-cost imaging method for xerostomia monitoring and assessment. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2012-01-01

Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3) induced the highest toxicity level to Daphnia magna(CE50,48 h = 2.21%). A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE50,30 min = 12.08%). All samples of pulp and paper wastes, and a textile waste (sample TX2) induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method. PMID:22619632

Acute and chronic toxicity of soluble fractions of industrial solid wastes on Daphnia magna and Vibrio fischeri.

PubMed

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

2012-01-01

Industrial wastes may produce leachates that can contaminate the aquatic ecosystem. Toxicity testing in acute and chronic levels is essential to assess environmental risks from the soluble fractions of these wastes, since only chemical analysis may not be adequate to classify the hazard of an industrial waste. In this study, ten samples of solid wastes from textile, metal-mechanic, and pulp and paper industries were analyzed by acute and chronic toxicity tests with Daphnia magna and Vibrio fischeri. A metal-mechanic waste (sample MM3) induced the highest toxicity level to Daphnia magna(CE(50,48 h) = 2.21%). A textile waste induced the highest toxicity level to Vibrio fischeri (sample TX2, CE(50,30 min) = 12.08%). All samples of pulp and paper wastes, and a textile waste (sample TX2) induced chronic effects on reproduction, length, and longevity of Daphnia magna. These results could serve as an alert about the environmental risks of an inadequate waste classification method.

Assessment of acute toxicity of carbofuran in Macrobrachium olfersii (Wiegmann, 1836) at different temperature levels.

PubMed

Barbieri, Edison; Moreira, Priscila; Luchini, Luiz Alberto; Hidalgo, Karla Ruiz; Muñoz, Alejandro

2016-01-01

Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate; C12H15NO3) is one of the most toxic carbamate pesticides. For acute toxicity of carbofuran, juveniles of Macrobrachium olfersii were exposed to different concentrations of carbofuran using the static renewal method at different temperature levels (15, 20 and 25°C) at pH 7.0. The main purpose of the present study was to detect the acute toxicity of carbofuran to M. olfersii and investigate its effects on oxygen consumption and ammonium excretion; these tests have not been carried out in this species before. First, the acute toxicity - median lethal concentration - of carbofuran to M. olfersii for 24, 48, 72 and 96 h was examined, which resulted in the following values: 1.64, 1.22, 0.86 and 0.42 mg L(-1), respectively. Furthermore, we also found that carbofuran caused an inhibition in oxygen consumption of 60.6, 65.3 and 66.2% with respect to the control. In addition, after separate exposures to carbofuran, elevations in ammonium excretion were more than 500% with respect to the control. © The Author(s) 2013.

Antibacterial activity of Aquilaria crassna leaf extract against Staphylococcus epidermidis by disruption of cell wall

PubMed Central

2013-01-01

Background Aquilaria crassna Pierre ex Lecomte has been traditionally used in Thailand for treatment of infectious diseases such as diarrhoea and skin diseases for a long time. The main objectives of this study were to examine antibacterial activity of the Aquilaria crassna leaf extract against Staphylococcus epidermidis and its underlying mechanism. The antioxidant activity and acute toxicity were studied as well. Methods Antioxidant activities were examined by FRAP, ABTS and DPPH scavenging methods. Antibacterial activity was conducted using disc diffusion assay and the minimum inhibitory concentration (MIC) was determined by dilution method. The minimum bactericidal concentration (MBC) was reported as the lowest concentration producing no growth of microbes in the subcultures. Morphological changes of the microbe were observed by scanning electron microscopy, while an inhibitory effect on biofilm formation was evaluated by phase contrast microscopic analysis. Bacterial cell wall integrity was assessed by transmission electron microscopy. Acute toxicity was conducted in accordance with the OECD for Testing of Chemicals (2001) guidelines. Results The extract exhibited considerable antioxidant activity. Staphylococcus epidermidis was susceptible to the extract with the MIC and MBC of 6 and 12 mg/ml, respectively. The extract caused swelling and distortion of bacterial cells and inhibited bacterial biofilm formation. Rupture of bacterial cell wall occurred after treated with the extract for 24 h. Acute toxicity test in mice showed no sign of toxicity or death at the doses of 2,000 and 15,000 mg/kg body weight. Conclusion The aqueous extract of Aquilaria crassna leaves possesses an in vitro antibacterial activity against Staphylococcus epidermidis, with no sign of acute oral toxicity in mice, probably by interfering with bacterial cell wall synthesis and inhibiting biofilm formation. PMID:23962360

Effect of AL2O3 and TiO2 nanoparticles on aquatic organisms

NASA Astrophysics Data System (ADS)

Gosteva, I.; Morgalev, Yu; Morgaleva, T.; Morgalev, S.

2015-11-01

Environmental toxicity of aqueous disperse systems of nanoparticles of binary compounds of titanium dioxides (with particle size Δ50=5 nm, Δ50=50 nm, Δ50=90 nm), aluminum oxide alpha-forms (Δ50=7 nm and Δ50=70 nm) and macro forms (TiO2 Δ50=350 nm, Al2O3 A50=4000 nm) were studied using biological testing methods. The bioassay was performed using a set of test organisms representing the major trophic levels. We found the dependence of the toxic effect concentration degree of nTiO2 and nAl2O3 on the fluorescence of the bacterial biosensor "Ekolyum", the chemotactic response of ciliates Paramecium caudatum, the growth of unicellular algae Chlorella vulgaris Beijer and mortality of entomostracans Daphnia magna Straus. We revealed the selective dependence of nTiO2 and nAl2O3 toxicity on the size, concentration and chemical nature of nanoparticles. The minimal concentration causing an organism's response on nTiO2 and nAl2O3 effect depends on the type of the test- organism and the test reaction under study. We specified L(E)C50 and acute toxicity categories for all the studied nanoparticles. We determined that nTiO2 (Δ50=5 nm) belong to the category «Acute toxicity 1», nTiO2 (A50=90 nm) and nAl2O3 (Δ50=70 nm) - to the category «Acute toxicity 2», nAl2O3 (Δ50=7 nm) - to the category «Acute toxicity 3». No acute toxicity was registered for nTiO2 (Δ50=50 nm) and macro form TiO2.

Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

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

Katayama, Sonja, E-mail: sonja.katayama@med.uni-heidelberg.de; Striecker, Thorbjoern; Kessel, Kerstin

Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy inmore » 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.« less

High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

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

Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus

Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracilmore » (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.« less

MEASURING THE ACUTE TOXICITY OF ESTUARINE SEDIMENTS

EPA Science Inventory

Estuarine sediments frequently are repositories and sources of anthropogenic contaminants. Toxicity is one method of assessing the environmental quality of sediments, yet because of the extreme range of salinities that characterize estuaries few infaunal organisms have both the p...

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

PubMed

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

2017-08-01

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

Acute toxicity of six freshwater mussel species (Glochidia) to six chemicals: Implications for daphnids and Utterbackia imbecillis as surrogates for protection of freshwater mussels (Unionidae)

USGS Publications Warehouse

Milam, C.D.; Farris, J.L.; Dwyer, F.J.; Hardesty, D.K.

2005-01-01

Acute (24-h) toxicity tests were used in this study to compare lethality responses in early life stages (glochidia) of six freshwater mussel species, Leptodea fragilis, U. imbecillis, Lampsilis cardium, Lampsilis siliquoidea, Megalonaias nervosa, and Ligumia subrostrata, and two standard test organisms, Ceriodaphnia dubia and Daphnia magna. Concentrations of carbaryl, copper, 4-nonylphenol, pentachlorophenol, permethrin, and 2,4-D were used in acute exposures to represent different chemical classes and modes of action. The relative sensitivities of species were evaluated by ranking their LC 50 values for each chemical. We used these ranks to determine the extent to which U. imbecillis (one of the most commonly used unionids in toxicity tests) was representative of the tolerances of other mussels. We also calculated geometric mean LC50s for the families Unionidae and Daphnidae. Rankings of these data were used to assess the extent to which Daphnidae can be used as surrogates for freshwater mussels relative to chemical sensitivity. While no single chemical elicited consistently high or low toxicity estimates, carbaryl and 2,4-D were generally the least toxic to all species tested. No species was always the most sensitive, and Daphnidae were generally protective of Unionidae. Utterbackia imbecillis, while often proposed as a standard unionid mussel test species, did not always qualify as a sufficient surrogate (i.e., a substitute organism that often elicits similar sensitivity responses to the same contaminant exposure) for other species of mussels, since it was usually one of the more tolerant species in our rankings. U. imbecillis should be used as a surrogate species only with this caution on its relative insensitivity. ?? 2005 Springer Science+Business Media, Inc.

SU-D-204-03: Comparison of Patient Positioning Methods Through Modeling of Acute Rectal Toxicity in Intensity Modulated Radiation Therapy for Prostate Cancer. Does Quality of Data Matter More Than the Quantity?

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

Liu, X; Fatyga, M; Vora, S

Purpose: To determine if differences in patient positioning methods have an impact on the incidence and modeling of grade >=2 acute rectal toxicity in prostate cancer patients who were treated with Intensity Modulated Radiation Therapy (IMRT). Methods: We compared two databases of patients treated with radiation therapy for prostate cancer: a database of 79 patients who were treated with 7 field IMRT and daily image guided positioning based on implanted gold markers (IGRTdb), and a database of 302 patients who were treated with 5 field IMRT and daily positioning using a trans-abdominal ultrasound system (USdb). Complete planning dosimetry was availablemore » for IGRTdb patients while limited planning dosimetry, recorded at the time of planning, was available for USdb patients. We fit Lyman-Kutcher-Burman (LKB) model to IGRTdb only, and Univariate Logistic Regression (ULR) NTCP model to both databases. We perform Receiver Operating Characteristics analysis to determine the predictive power of NTCP models. Results: The incidence of grade >= 2 acute rectal toxicity in IGRTdb was 20%, while the incidence in USdb was 54%. Fits of both LKB and ULR models yielded predictive NTCP models for IGRTdb patients with Area Under the Curve (AUC) in the 0.63 – 0.67 range. Extrapolation of the ULR model from IGRTdb to planning dosimetry in USdb predicts that the incidence of acute rectal toxicity in USdb should not exceed 40%. Fits of the ULR model to the USdb do not yield predictive NTCP models and their AUC is consistent with AUC = 0.5. Conclusion: Accuracy of a patient positioning system affects clinically observed toxicity rates and the quality of NTCP models that can be derived from toxicity data. Poor correlation between planned and clinically delivered dosimetry may lead to erroneous or poorly performing NTCP models, even if the number of patients in a database is large.« less

Urinary and Rectal Toxicity Profiles After Permanent Iodine-125 Implant Brachytherapy in Japanese Men: Nationwide J-POPS Multi-institutional Prospective Cohort Study

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

Ohashi, Toshio, E-mail: ohashi@rad.med.keio.ac.jp; Yorozu, Atsunori; Saito, Shiro

Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT). Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiationmore » therapy. Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment. Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies.« less

Feasibility and radiation induced toxicity regarding the first application of transperineal implementation of biocompatible balloon for high dose radiotherapy in patients with prostate carcinoma

PubMed Central

2013-01-01

Objective To evaluate the feasibility of the transperineal implementation of biocompatible balloon (Prospace) and the acute toxicity of high dose 3DCRT in patients with localized low risk prostate cancer. Materials and methods Between December 2011 and April 2012, fifteen patients were treated with external 3DCRT consisted of 76–78 Gy in 38–39 daily fractions (2.0 Gy/ fraction). Before 3DCRT, we placed the Prospace though the perineum by a minimally invasive procedure in the intermediate space between the rectum and the prostate. The primary study endpoint was the evaluation of acute toxicity according to the EORTC/RTOG radiation toxicity scale. Erectile function was evaluated with the IIEF-5 questionnaire. Rectosigmoidoscopy was performed at baseline, at the end of 3DCRT and 3 months thereafter in order to assess also the rectal toxicity according to Subjective-RectoSigmoid (S-RS) scale. The evaluation of pain related to Prospace implementation was done with the visual analogue score (VAS). Results The acute toxicities were as follows: grade I GI toxicity in two patients and for GU toxicity, three patients with grade I of nocturia, four patients with grade I of frequency, two patients with grade I and two patients with grade II of dysouria. The mean score of rectal toxicity according to S-RS score was 1.8(±0.6). The mean VAS score related to Prospace was 1.4(±0.5). Erectile function was unchanged. The Prospace device was found stable in sequential CTs during irradiation. Conclusions The implementation of PROSPACE was feasible, while the acute radiation toxicity was low and comparable with IMRT techniques. PMID:23566526

Toxicity Assessment of Pelvic Intensity-Modulated Radiotherapy With Hypofractionated Simultaneous Integrated Boost to Prostate for Intermediate- and High-Risk Prostate Cancer

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

McCammon, Robert; Rusthoven, Kyle E.; Kavanagh, Brian

Purpose: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. Methods and Materials: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to scoremore » toxicity. Results: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving {>=}25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving {>=}50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Conclusion: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.« less

Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

PubMed

Yuan, Guiping; Dai, Shujun; Yin, Zhongqiong; Lu, Hongke; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li; Shu, Yang; Zhao, Xinghong

2014-03-01

The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days. Copyright © 2014 Elsevier Ltd. All rights reserved.

Predicting acute toxicity of traditional Chinese medicine wastewater using UV absorption and volatile fatty acids as surrogates.

PubMed

Lv, Longyi; Li, Weiguang; Yu, Yang; Meng, Liqiang; Qin, Wen; Wu, Chuandong

2018-03-01

In this study, the applicability of UV absorbance at 254 nm (UV 254 ) and volatile fatty acids (VFAs) to serve as reliable surrogates to predict acute toxicity of traditional Chinese medicine (TCM) wastewater was investigated. The medicine residues and VFAs were identified as main components of the TCM wastewater, and their individual and joint toxicity assays were operated with luminescent bacteria. The median effective concentration (EC 50 ) values of medicine residues and VFAs were in the range of 26.46-165.55 mg/L and 11.45-20.58 g/L, respectively. The joint toxicity action modes of medicine residues, VFAs and medicine residues-VFAs were identified as additive, additive and synergistic respectively. UV 254 and VFAs showed better correlations with acute toxicity according to the correlation analysis, compared with other conventional parameters. The regression model was a good fit for toxic unit (TU 50 ) as a function of UV 254 and VFAs according to the stepwise regression method (adjusted R 2  = 0.836). Validation of the model to the pilot-scale samples provided satisfactory prediction results in the influent and hydrolysis acidification effluent samples tests, but for EGSB effluent and final effluent samples, the model needed further optimization. Surrogates prediction using UV 254 and VFAs provided a valuable and cost-saving tool for rapid or on-line monitoring of acute toxicity of TCM wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

PubMed Central

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Objectives: Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). Materials and Methods: In vivo toxicity studies were performed in male balb ‘C’ mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. Results: No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement. PMID:23087514

Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival

PubMed Central

Ongaro, Alessia; De Mattei, Monica; Della Porta, Matteo Giovanni; Rigolin, GianMatteo; Ambrosio, Cristina; Di Raimondo, Francesco; Pellati, Agnese; Masieri, Federica Francesca; Caruso, Angelo; Catozzi, Linda; Gemmati, Donato

2009-01-01

Background The antifolate agent methotrexate is an important component of maintenance therapy in acute lymphoblastic leukemia, although methotrexate-related toxicity is often a reason for interruption of chemotherapy. Prediction of toxicity is difficult because of inter-individual variability susceptibility to antileukemic agents. Methotrexate interferes with folate metabolism leading to depletion of reduced folates. Design and Methods The aim of this study was to investigate the influence of polymorphisms for folate metabolizing enzymes with respect to toxicity and survival in adult patients with acute lymphoblastic leukemia treated with methotrexate maintenance therapy. To this purpose, we evaluated possible associations between genotype and hematologic and non-hematologic toxicity and effects on survival at 2 years of follow-up in patients with acute lymphoblastic leukemia. Results Polymorphisms in the genes encoding for methylenetetrahydrofolate reductase (MTHFR 677C>T) and in dihydrofolate reductase (DHFR 19 bp deletion) significantly increased the risk of hepatotoxicity in single (odds ratio 5.23, 95% confidence interval 1.13–21.95 and odds ratio 4.57, 95% confidence interval 1.01–20.77, respectively) and in combined analysis (odds ratio 6.82, 95% confidence interval 1.38–33.59). MTHFR 677C>T also increased the risk of leukopenia and gastrointestinal toxicity, whilst thymidylate synthase 28 bp repeat polymorphism increased the risk of anemia (odds ratio 8.48, 95% confidence interval 2.00–36.09). Finally, patients with MTHFR 677TT had a decreased overall survival rate (hazard ratio 2.37, 95% confidence interval 1.46–8.45). Conclusions Genotyping of folate polymorphisms might be useful in adult acute lymphoblastic leukemia to optimize methotrexate therapy, reducing the associated toxicity with possible effects on survival. PMID:19648163

Acute toxicity assessment of explosive-contaminated soil extracting solution by luminescent bacteria assays.

PubMed

Xu, Wenjie; Jiang, Zhenming; Zhao, Quanlin; Zhang, Zhenzhong; Su, Hongping; Gao, Xuewen; Ye, Zhengfang

2016-11-01

Explosive-contaminated soil is harmful to people's health and the local ecosystem. The acute toxicity of its extracting solution was tested by bacterial luminescence assay using three kinds of luminescent bacteria to characterize the toxicity of the soil. An orthogonal test L 16 (4 5 ) was designed to optimize the soil extracting conditions. The optimum extracting conditions were obtained when the ultrasonic extraction time, ultrasonic extraction temperature, and the extraction repeat times were 6 h, 40 °C, and three, respectively. Fourier transform infrared spectroscopy (FTIR) results showed that the main components of the contaminated soil's extracting solution were 2,4-dinitrotoluene-3-sulfonate (2,4-DNT-3-SO 3 - ); 2,4-dinitrotoluene-5-sulfonate (2,4-DNT-5-SO 3 - ); and 2,6-dinitrotoluene (2,6-DNT). Compared with Photobacterium phosphoreum and Vibrio fischeri, Vibrio qinghaiensis sp. Nov. is more suitable for assessing the soil extracting solution's acute toxicity. Soil washing can remove most of the contaminants toxic to luminescent bacterium Vibrio qinghaiensis sp. Nov., suggesting that it may be a potential effective remediation method for explosive-contaminated soil.

Experimental toxicology of pyrolysis and combustion hazards.

PubMed Central

Cornish, H H; Hahn, K J; Barth, M L

1975-01-01

Data are presented on the acute toxicity (mortality only) of the thermal degradation products of polymers obtained by two methods of degradation. One system utilized a slowly increasing temperature (5 degrees C/min) and gradual degradation of the polymer with the rats being exposed to degradation products as they were evolved. In this system the more toxic polymers included wool, polypropylene, poly(vinyl chloride), and urethane foam. The second system utilized conditions of rapid combustion and exposure of rats to the total products of combustion for a period of 4 hr. In this system the more toxic materials included red oak, cotton, acrylonitrile-butadiene-styrene (ABS), and styrene-acrylonitrile. It is of interest to note that the natural product wool is among the least toxic under these rapid combustion conditions and among the most toxic under slow pyrolysis conditions. Other materials also vary in the comparative toxicity of their thermal degradation products, depending upon the conditions of degradation and animal exposure. The two experimental techniques presented here may well represent the two extreme conditions of rapid combustion versus slow pyrolysis. Intermediate types of fire situations might be expected to result in relative acute toxicities somewhere between these two extremes. This report deals with acute toxicity on the basis of mortality data only and does not include other parameters of toxicity such as organ weights and histopathology. PMID:1175552

Methods, safety, and early clinical outcomes of dose escalation using simultaneous integrated and sequential boosts in patients with locally advanced gynecologic malignancies.

PubMed

Boyle, John; Craciunescu, Oana; Steffey, Beverly; Cai, Jing; Chino, Junzo

2014-11-01

To evaluate the safety of dose escalated radiotherapy using a simultaneous integrated boost technique in patients with locally advanced gynecological malignancies. Thirty-nine women with locally advanced gynecological malignancies were treated with intensity modulated radiation therapy utilizing a simultaneous integrated boost (SIB) technique for gross disease in the para-aortic and/or pelvic nodal basins, sidewall extension, or residual primary disease. Women were treated to 45Gy in 1.8Gy fractions to elective nodal regions. Gross disease was simultaneously treated to 55Gy in 2.2Gy fractions (n=44 sites). An additional sequential boost of 10Gy in 2Gy fractions was delivered if deemed appropriate (n=29 sites). Acute and late toxicity, local control in the treated volumes (LC), overall survival (OS), and distant metastases (DM) were assessed. All were treated with a SIB to a dose of 55Gy. Twenty-four patients were subsequently treated with a sequential boost to a median dose of 65Gy. Median follow-up was 18months. Rates of acute>grade 2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 2.5%, 0%, and 30%, respectively. There were no grade 4 acute toxicities. At one year, grade 1-2 late GI toxicities were 24.5%. There were no grade 3 or 4 late GI toxicities. Rates of grade 1-2 late GU toxicities were 12.7%. There were no grade 3 or 4 late GU toxicities. Dose escalated radiotherapy using a SIB results in acceptable rates of acute toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Regorafenib induced severe toxic hepatitis: characterization and discussion.

PubMed

Sacré, Anne; Lanthier, Nicolas; Dano, Hélène; Aydin, Selda; Leggenhager, Daniela; Weber, Achim; Dekairelle, Anne-France; De Cuyper, Astrid; Gala, Jean-Luc; Humblet, Yves; Sempoux, Christine; Van den Eynde, Marc

2016-11-01

Regorafenib is the first small-molecule multikinase inhibitor which showed survival benefits in pretreated metastatic colorectal cancer (mCRC) patients. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. Patients with refractory mCRC treated with regorafenib in our institution were reviewed. Severe treatment-related liver toxicity was investigated. Clinical history, liver histology and genetic assessment (sequence analysis) of cytochrome P3A4 (CYP3A4) and uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) involved in regorafenib metabolization were here reported for patients with severe hepatotoxicity. Among the 93 reviewed patients, 3 presented severe and icteric toxic hepatitis which was fatal for 1 patient. Histopathological liver lesions were different depending on the onset of hepatotoxicity (acute or subacute): acinar zone 3 necrosis in case of acute symptoms, and portal tract inflammation with porto-central bridging and fibrosis in the delayed presentation. None of the patients had CYP3A4 gene mutations. Similar polymorphisms in UGT1A9 gene promoter region (UGT1A9 variant -118T 9>10 [rs3832043]) were found in both patients who presented acute hepatitis. Moreover, it appears retrospectively that both of them already experienced significant toxicity under irinotecan-based chemotherapy. This is the first report of severe hepatotoxicity with available liver histology and genetic assessment of enzymes involved in regorafenib metabolization. This report also reminds the importance of close liver tests monitoring during regorafenib treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vivo dosimetry and acute toxicity in breast cancer patients undergoing intraoperative radiotherapy as boost

PubMed Central

Lee, Jason Joon Bock; Choi, Jinhyun; Ahn, Sung Gwe; Jeong, Joon; Lee, Ik Jae; Park, Kwangwoo; Kim, Kangpyo; Kim, Jun Won

2017-01-01

Purpose To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. Materials and Methods Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. Results Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. conclusions IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost. PMID:28712278

Acute and subacute toxicity and chemical constituents of the hydroethanolic extract of Verbena litoralis Kunth.

PubMed

de Lima, Rachel; Guex, Camille Gaube; da Silva, Andreia Regina Haas; Lhamas, Cibele Lima; Dos Santos Moreira, Karen Luise; Casoti, Rosana; Dornelles, Rafaela Castro; Marques da Rocha, Maria Izabel Ugalde; da Veiga, Marcelo Leite; de Freitas Bauermann, Liliane; Manfron, Melânia Palermo

2018-05-14

Verbena litoralis Kunth is a native species of South America, popularly known as gervãozinho-do-campo ou erva-de-pai-caetano. It is used in gastrointestinal disorders, as detoxifying the organism, antifebrile properties and amidaglitis. To identify the chemical constituents of the hydroethanolic extract obtained from the aerial parts of V. litoralis and to evaluate the acute and sub-acute toxicity in male and female rats. The single dose (2000 mg/kg) of the extract was administered orally to male and female rats. In the subacute study the extract was given at doses of 100, 200 and 400mg/kg during 28 days orally. Biochemical, hematological and histological analyzes were performed, oxidative stress markers were tested and chemical constituents were identified through UHPLC-ESI-HRMS RESULTS: Six classes of metabolites were identified: iridoids glycosides, flavonoids, phenylpropanoids-derived, phenylethanoid-derived, cinnamic acid-derived and triterpenes. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. Our results demonstrated that subacute administration of the crude extract of V. litoralis at 400mg/kg resulted in an increase in AST in males, whereas ALT enzyme showed a small increase in males that received 200mg/kg and 400mg/kg of the extract. The extract of the aerial parts of Verbena litoralis did not present significant toxicity when administered a single dose. However, when different doses were administered for 28 days, were observed changes in hematological, biochemical and histological parameters in rats. Copyright © 2018. Published by Elsevier B.V.

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.

Assessment of in vivo systemic toxicity and biodistribution of iron-doped silica nanoshells.

PubMed

Mendez, Natalie; Liberman, Alexander; Corbeil, Jacqueline; Barback, Christopher; Viveros, Robert; Wang, James; Wang-Rodriguez, Jessica; Blair, Sarah L; Mattrey, Robert; Vera, David; Trogler, William; Kummel, Andrew C

2017-04-01

Silica nanoparticles are an emerging class of biomaterials which may be used as diagnostic and therapeutic tools for biomedical applications. In particular, hollow silica nanoshells are attractive due to their hollow core. Approximately 70% of a 500 nm nanoshell is hollow, therefore more particles can be administered on a mg/kg basis compared to solid nanoparticles. Additionally, their nanoporous shell permits influx/efflux of gases and small molecules. Since the size, shape, and composition of a nanoparticle can dramatically alter its toxicity and biodistribution, the toxicology of these nanomaterials was assessed. A single dose toxicity study was performed in vivo to assess the toxicity of 500 nm iron-doped silica nanoshells at clinically relevant doses of 10-20 mg/kg. This study showed that only a trace amount of silica was detected in the body 10 weeks post-administration. The hematology, biochemistry and pathological results show that the nanoshells exhibit no acute or chronic toxicity in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Pesticide knowledge, practice and attitude and how it affects the health of small-scale farmers in Uganda: a cross-sectional study.

PubMed

Oesterlund, Anna H; Thomsen, Jane F; Sekimpi, Deogratias K; Maziina, James; Racheal, Apio; Jørs, Erik

2014-06-01

Over the past years there has been an increase in the use of pesticides in developing countries. This study describes pesticide use among small-scale farmers in Uganda and analyses predictors of pesticide poisoning (intoxication) symptoms. A cross-sectional study was conducted using a standardized questionnaire. Some 317 small-scale farmers in two districts in Uganda were interviewed about pesticide use, knowledge and attitude, symptoms of intoxication, personal protective equipment (PPE) and hygiene. The risk of reporting symptoms was analysed using logistic regression analysis. The most frequently used pesticides belonged to WHO class II. The farmers had poor knowledge about pesticide toxicity, and the majority did not use appropriate PPE nor good hygiene when handling pesticides. There was no significant association between the number of times of spraying with pesticides and self-reported symptoms of pesticide poisoning. The only significant association was between blowing and sucking the nozzle of the knapsack sprayer and self-reported symptoms of pesticide intoxication (OR: 2.13. 95% CI: 1.09 - 4.18). Unlike the practice in several other developing countries, small-scale farmers in Uganda do not use the most hazardous pesticides (WHO class 1a and 1b). However use of WHO class II pesticides and those of lower toxicity is seen in combination with inadequate knowledge and practice among the farmers. This poses a danger of acute intoxications, chronic health problems and environmental pollution. Training of farmers in Integrated Pest Management (IPM) methods, use of proper hygiene and personal protective equipment when handling pesticides should be promoted.

Evaluating aquatic invertebrate vulnerability to insecticides based on intrinsic sensitivity, biological traits, and toxic mode of action.

PubMed

Rico, Andreu; Van den Brink, Paul J

2015-08-01

In the present study, the authors evaluated the vulnerability of aquatic invertebrates to insecticides based on their intrinsic sensitivity and their population-level recovery potential. The relative sensitivity of invertebrates to 5 different classes of insecticides was calculated at the genus, family, and order levels using the acute toxicity data available in the US Environmental Protection Agency ECOTOX database. Biological trait information was linked to the calculated relative sensitivity to evaluate correlations between traits and sensitivity and to calculate a vulnerability index, which combines intrinsic sensitivity and traits describing the recovery potential of populations partially exposed to insecticides (e.g., voltinism, flying strength, occurrence in drift). The analysis shows that the relative sensitivity of arthropods depends on the insecticide mode of action. Traits such as degree of sclerotization, size, and respiration type showed good correlation to sensitivity and can be used to make predictions for invertebrate taxa without a priori sensitivity knowledge. The vulnerability analysis revealed that some of the Ephemeroptera, Plecoptera, and Trichoptera taxa were vulnerable to all insecticide classes and indicated that particular gastropod and bivalve species were potentially vulnerable. Microcrustaceans (e.g., daphnids, copepods) showed low potential vulnerability, particularly in lentic ecosystems. The methods described in the present study can be used for the selection of focal species to be included as part of ecological scenarios and higher tier risk assessments. © 2015 SETAC.

Risk of Severe Toxicity According to Site of Recurrence in Patients Treated With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer

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

Ling, Diane C.; Vargo, John A.; Ferris, Robert L.

Purpose: To report a 10-year update of our institutional experience with stereotactic body radiation therapy (SBRT) for reirradiation of locally recurrent head and neck cancer, focusing on predictors of toxicity. Methods and Materials: A retrospective review was performed on 291 patients treated with SBRT for recurrent, previously irradiated head and neck cancer between April 2002 and March 2013. Logistic regression analysis was performed to identify predictors of severe acute and late toxicity. Patients with <3 months of follow-up (n=43) or who died within 3 months of treatment (n=21) were excluded from late toxicity analysis. Results: Median time to death or last clinicalmore » follow-up was 9.8 months among the entire cohort and 53.1 months among surviving patients. Overall, 33 patients (11.3%) experienced grade ≥3 acute toxicity and 43 (18.9%) experienced grade ≥3 late toxicity. Compared with larynx/hypopharynx, treatment of nodal recurrence was associated with a lower risk of severe acute toxicity (P=.03), with no significant differences in severe acute toxicity among other sites. Patients treated for a recurrence in the larynx/hypopharynx experienced significantly more severe late toxicity compared with those with oropharyngeal, oral cavity, base of skull/paranasal sinus, salivary gland, or nodal site of recurrence (P<.05 for all). Sixteen patients (50%) with laryngeal/hypopharyngeal recurrence experienced severe late toxicity, compared with 6-20% for other sites. Conclusions: Salvage SBRT is a safe and effective option for most patients with previously irradiated head and neck cancer. However, patients treated to the larynx or hypopharynx experience significantly more late toxicity compared with others and should be carefully selected for treatment, with consideration given to patient performance status, pre-existing organ dysfunction, and goals of care. Treatment toxicity in these patients may be mitigated with more conformal plans to allow for increased sparing of adjacent normal tissues.« less

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.

Clone- and age-dependent toxicity of a glyphosate commercial formulation and its active ingredient in Daphnia magna.

PubMed

Cuhra, Marek; Traavik, Terje; Bøhn, Thomas

2013-03-01

Low levels of glyphosate based herbicide induced significant negative effects on the aquatic invertebrate Daphnia magna. Glyphosate herbicides such as brands of Roundup, are known to be toxic to daphnids. However, published findings on acute toxicity show significant discrepancies and variation across several orders of magnitude. To test the acute effects of both glyphosate and a commercial formulation of Roundup (hereafter Roundup), we conducted a series of exposure experiments with different clones and age-classes of D. magna. The results demonstrated EC(50) (48) values in the low ppm-range for Roundup as well as for the active ingredient (a.i.) isopropylamine salt of glyphosate (glyphosate IPA) alone. Roundup showed slightly lower acute toxicity than glyphosate IPA alone, i.e. EC(50) values of 3.7-10.6 mg a.i./l, as compared to 1.4-7.2 mg a.i./l for glyphosate IPA. However, in chronic toxicity tests spanning the whole life-cycle, Roundup was more toxic. D. magna was exposed to sublethal nominal concentrations of 0.05, 0.15, 0.45, 1.35 and 4.05 mg a.i./l for 55 days. Significant reduction of juvenile size was observed even in the lowest test concentrations of 0.05 mg a.i./l, for both glyphosate and Roundup. At 0.45 mg a.i./l, growth, fecundity and abortion rate was affected, but only in animals exposed to Roundup. At 1.35 and 4.05 mg a.i./l of both glyphosate and Roundup, significant negative effects were seen on most tested parameters, including mortality. D. magna was adversely affected by a near 100 % abortion rate of eggs and embryonic stages at 1.35 mg a.i./l of Roundup. The results indicate that aquatic invertebrate ecology can be adversely affected by relevant ambient concentrations of this major herbicide. We conclude that glyphosate and Roundup toxicity to aquatic invertebrates have been underestimated and that current European Commission and US EPA toxicity classification of these chemicals need to be revised.

Acute and subacute oral toxicity of polychlorinated diphenyl sulfides in mice: determining LD50 and assessing the status of hepatic oxidative stress.

PubMed

Zhang, Xuesheng; Liu, Fu; Chen, Binyuan; Li, Ying; Wang, Zunyao

2012-07-01

Polychlorinated diphenyl sulfides (PCDPSs), a series of dioxin-like compounds, have been detected in various environmental samples. However, information on the toxicity of these compounds is limited. In the present study, the toxic effects of PCDPSs were assessed after acute and subacute exposure in mice. Relationships between acute toxicity, number, and position of substituted Cl atoms were assessed. In the acute study, 11 types of PCDPSs were administered to female Kunming mice by gavage, and median lethal doses (LD50s) were determined by the Karber method. Results indicated that the LD50s of lower substituted PCDPSs were smaller than higher substituted PCDPSs. Substituted positions also influenced the LD50 of PCDPSs. Terminal necropsy showed increased relative liver weights and decreased relative kidney weights. Histological examination of livers demonstrated swollen cells, inflammation, vacuolization, and necrosis. In the 28-d subacute exposure tests, 11 types of PCDPSs were dissolved in corn oil and administered to mice at doses of 1, 10, and 100 mg/kg. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in mouse liver were determined after the exposure period. Results suggested that lower substituted PCDPSs decreased SOD activity in the high-dose groups compared with controls, and MDA level in the 100-mg/kg dose group was significantly increased. In addition, acute toxicity of PCDPSs partly corresponded to the hepatic oxidative damage observed. Copyright © 2012 SETAC.

[Living conditions and pattern of acute poisonings in Oslo].

PubMed

Kolvik, Hallgeir Mæsel; Heyerdahl, Fridtjof; Bjørnaas, Mari Asphjell; Hovda, Knut Erik; Jacobsen, Dag; Ekeberg, Øivind

2011-08-09

Hospitalized patients with acute poisoning come from all classes of society. The relationship between living conditions and pattern of poisoning is, however, unclear. The aim of this study was to examine the connection between living conditions in Oslo and the pattern of acute poisonings, measured by incidence, main toxic agents and intention. A one-year multi-centre study with prospective inclusion of all patients ≥ 18 years of age with a registered address in Oslo admitted to an Oslo hospital with acute poisoning from 1 April 2003 through 31 March 2004. The 15 city districts were grouped into three, according to the official living conditions index in Oslo: city district group 1 (best living conditions), city district group 2 (average living conditions) and city district group 3 (most difficult living conditions). Of a total of 947 patients admitted with acute poisoning as their main diagnosis in the study period, 691 were included in the study, 660 of whom had self-inflicted poisoning. In city district group 3, the annual incidence of acute poisonings was 2.14 per 1000 inhabitants, significantly higher than city district group 2, with 1.50 (p < 0.001), and city district group 1, with 1.36 (p < 0.001). Measured as intention assessed by the treating physician, suicidal and drug related poisonings and those induced by a "cry for help" were more common in city district group 3 (0.74, 0.59 and 0.74 per 1000 inhabitants, respectively) than in city district group 2 (0.62, 0.40 and 0.41, respectively) and city district group 1 (0.52, 0.32 and 0.45, respectively). The main toxic agents were predominantly benzodiazepines (20 %), ethanol (18 %) and paracetamol (12 %). There were no statistically significant differences in the distribution of main toxic agents between the city district groups. The findings show a social gradient, with the highest incidence of poisonings in the city district group with the most difficult living conditions.

Study on acute toxicity of anti-vertigo granule on mice

NASA Astrophysics Data System (ADS)

Wen, Zhonghua; Hao, Shaojun; Xie, Guoqi; Li, Jun; Su, Feng; Liu, Xiaobin; Wang, Xidong; Zhang, Zhengchen

2018-04-01

To observe the effect of anti - glare particles on acute toxicity of mice. Methods: 40 male and female mice weighing 18 - 21 g were randomly divided into anti - glare granule group and normal saline control group. The maximum volume of anti - glare particles (0.94 g/ml) was administered before the experiment. Results: the oral toxicity of the suspension was very small. The maximal concentration of mice was given at the maximum volume of gastric perfusion, and it was given three times in 1st. The cumulative maximum tolerance dose was 112.8g/kg per day. The dose was 226 times of clinical dosage and no death was found in mice. Conclusion: the toxicity of Kangxuan granules is very small and it can be considered safe in clinical use.

Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study

PubMed Central

Junius, Sara; Haustermans, Karin; Bussels, Barbara; Oyen, Raymond; Vanstraelen, Bianca; Depuydt, Tom; Verstraete, Jan; Joniau, Steven; Van Poppel, Hendrik

2007-01-01

Background To assess acute (primary endpoint) and late toxicity, quality of life (QOL), biochemical or clinical failure (secondary endpoints) of a hypofractionated IMRT schedule for prostate cancer (PC). Methods 38 men with localized PC received 66 Gy (2.64 Gy) to prostate,2 Gy to seminal vesicles (50 Gy total) using IMRT. Acute toxicity was evaluated weekly during radiotherapy (RT), at 1–3 months afterwards using RTOG acute scoring system. Late side effects were scored at 6, 9, 12, 16, 20, 24 and 36 months after RT using RTOG/EORTC criteria. Quality of life was assessed by EORTC-C30 questionnaire and PR25 prostate module. Biochemical failure was defined using ASTRO consensus and nadir+2 definition, clinical failure as local, regional or distant relapse. Results None experienced grade III-IV toxicity. 10% had no acute genito-urinary (GU) toxicity, 63% grade I; 26% grade II. Maximum acute gastrointestinal (GI) scores 0, I, II were 37%, 47% and 16%. Maximal acute toxicity was reached weeks 4–5 and resolved within 4 weeks after RT in 82%. Grade II rectal bleeding needing coagulation had a peak incidence of 18% at 16 months after RT but is 0% at 24–36 months. One developed a urethral stricture at 2 years (grade II late GU toxicity) successfully dilated until now. QOL urinary symptom scores reached a peak incidence 1 month after RT but normalized 6 months later. Bowel symptom scores before, at 1–6 months showed similar values but rose slowly 2–3 years after RT. Nadir of sexual symptom scores was reached 1–6 months after RT but improved 2–3 years later as well as physical, cognitive and role functional scales. Emotional, social functional scales were lowest before RT when diagnosis was given but improved later. Two years after RT global health status normalized. Conclusion This hypofractionated IMRT schedule for PC using 25 fractions of 2.64 Gy did not result in severe acute side effects. Until now late urethral, rectal toxicities seemed acceptable as well as failure rates. Detailed analysis of QOL questionnaires resulted in the same conclusion. PMID:17686162

Class effect of pharmacotherapy in bipolar disorder: fact or misbelief?

PubMed Central

2011-01-01

Background Anecdotal reports suggests that most clinicians treat medications as belonging to a class with regard to all therapeutic indications; this means that the whole 'class' of drugs is considered to possesses a specific therapeutic action. The present article explores the possible existence of a true 'class effect' for agents available for the treatment of bipolar disorder. Methods We reviewed the available treatment data from randomized controlled trials (RCTs) and explored 16 'agent class'/'treatment issue' cases for bipolar disorder. Four classes of agents were examined: first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs), antiepileptics and antidepressants, with respect to their efficacy on four treatment issues of bipolar disorder (BD) (acute mania, acute bipolar depression, maintenance against mania, maintenance against depression). Results From the 16 'agent class'/' treatment issue' cases, only 3 possible class effects were detected, and they all concerned acute mania and antipsychotics. Four effect cases have not been adequately studied (FGAs against acute bipolar depression and in maintenance protection from depression, and antidepressants against acute mania and protection from mania) and they all concern treatment cases with a high risk of switching to the opposite pole, thus research in these areas is poor. There is no 'class effect' at all concerning antiepileptics. Conclusions The available data suggest that a 'class effect' is the exception rather than the rule in the treatment of BD. However, the possible presence of a 'class effect' concept discourages clinicians from continued scientific training and reading. Focused educational intervention might be necessary to change this attitude. PMID:21435226

Acute toxic nephropathies: clinical pathologic correlations.

PubMed

Muehrcke, R C; Volini, F I; Morris, A M; Moles, J B; Lawrence, A G

1976-01-01

Man's ever increasing exposure to numerous drugs and chemicals, which are the results of medical and industrial progress, produces a by-product of acute toxic nephropathies. These include acute toxic renal failure, drug-induced acute oliguric renal failure, acute hemorrhagic glomerulonephritis, nephrotic syndrome, tubular disturbances and potassium deficiency. In depth information is provided for the previously mentioned disorders.

BitterSweetForest: A random forest based binary classifier to predict bitterness and sweetness of chemical compounds

NASA Astrophysics Data System (ADS)

Banerjee, Priyanka; Preissner, Robert

2018-04-01

Taste of a chemical compounds present in food stimulates us to take in nutrients and avoid poisons. However, the perception of taste greatly depends on the genetic as well as evolutionary perspectives. The aim of this work was the development and validation of a machine learning model based on molecular fingerprints to discriminate between sweet and bitter taste of molecules. BitterSweetForest is the first open access model based on KNIME workflow that provides platform for prediction of bitter and sweet taste of chemical compounds using molecular fingerprints and Random Forest based classifier. The constructed model yielded an accuracy of 95% and an AUC of 0.98 in cross-validation. In independent test set, BitterSweetForest achieved an accuracy of 96 % and an AUC of 0.98 for bitter and sweet taste prediction. The constructed model was further applied to predict the bitter and sweet taste of natural compounds, approved drugs as well as on an acute toxicity compound data set. BitterSweetForest suggests 70% of the natural product space, as bitter and 10 % of the natural product space as sweet with confidence score of 0.60 and above. 77 % of the approved drug set was predicted as bitter and 2% as sweet with a confidence scores of 0.75 and above. Similarly, 75% of the total compounds from acute oral toxicity class were predicted only as bitter with a minimum confidence score of 0.75, revealing toxic compounds are mostly bitter. Furthermore, we applied a Bayesian based feature analysis method to discriminate the most occurring chemical features between sweet and bitter compounds from the feature space of a circular fingerprint.

BitterSweetForest: A Random Forest Based Binary Classifier to Predict Bitterness and Sweetness of Chemical Compounds

PubMed Central

Banerjee, Priyanka; Preissner, Robert

2018-01-01

Taste of a chemical compound present in food stimulates us to take in nutrients and avoid poisons. However, the perception of taste greatly depends on the genetic as well as evolutionary perspectives. The aim of this work was the development and validation of a machine learning model based on molecular fingerprints to discriminate between sweet and bitter taste of molecules. BitterSweetForest is the first open access model based on KNIME workflow that provides platform for prediction of bitter and sweet taste of chemical compounds using molecular fingerprints and Random Forest based classifier. The constructed model yielded an accuracy of 95% and an AUC of 0.98 in cross-validation. In independent test set, BitterSweetForest achieved an accuracy of 96% and an AUC of 0.98 for bitter and sweet taste prediction. The constructed model was further applied to predict the bitter and sweet taste of natural compounds, approved drugs as well as on an acute toxicity compound data set. BitterSweetForest suggests 70% of the natural product space, as bitter and 10% of the natural product space as sweet with confidence score of 0.60 and above. 77% of the approved drug set was predicted as bitter and 2% as sweet with a confidence score of 0.75 and above. Similarly, 75% of the total compounds from acute oral toxicity class were predicted only as bitter with a minimum confidence score of 0.75, revealing toxic compounds are mostly bitter. Furthermore, we applied a Bayesian based feature analysis method to discriminate the most occurring chemical features between sweet and bitter compounds using the feature space of a circular fingerprint. PMID:29696137

Pesticides: an update of human exposure and toxicity.

PubMed

Mostafalou, Sara; Abdollahi, Mohammad

2017-02-01

Pesticides are a family of compounds which have brought many benefits to mankind in the agricultural, industrial, and health areas, but their toxicities in both humans and animals have always been a concern. Regardless of acute poisonings which are common for some classes of pesticides like organophosphoruses, the association of chronic and sub-lethal exposure to pesticides with a prevalence of some persistent diseases is going to be a phenomenon to which global attention has been attracted. In this review, incidence of various malignant, neurodegenerative, respiratory, reproductive, developmental, and metabolic diseases in relation to different routes of human exposure to pesticides such as occupational, environmental, residential, parental, maternal, and paternal has been systematically criticized in different categories of pesticide toxicities like carcinogenicity, neurotoxicity, pulmonotoxicity, reproductive toxicity, developmental toxicity, and metabolic toxicity. A huge body of evidence exists on the possible role of pesticide exposures in the elevated incidence of human diseases such as cancers, Alzheimer, Parkinson, amyotrophic lateral sclerosis, asthma, bronchitis, infertility, birth defects, attention deficit hyperactivity disorder, autism, diabetes, and obesity. Most of the disorders are induced by insecticides and herbicides most notably organophosphorus, organochlorines, phenoxyacetic acids, and triazine compounds.

Synthesis, cytotoxicity and haemolytic activity of Pulsatilla saponin A, D derivatives.

PubMed

Chen, Zhong; Duan, Huaqing; Wang, Minglei; Han, Li; Liu, Yanli; Zhu, Yongming; Yang, Shilin

2015-06-15

The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered their clinical development of antitumor agents. In order to solve this problem, C-28 position modification derivatives of PSA/PSD were synthesized. The cytotoxicity and haemolytic activity of these compounds were evaluated. Structure-activity relationship and structure-toxicity relationship had been observed. The mice acute toxicity of compound 11 was reduced greatly than that of PSA. This study indicates that compound 11 may represent an interesting class of potent antitumor agents from triterpenoid saponins avoiding the haemolysis problem. The present study has important significance for the development of antitumor saponins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of an acute oral gavage method for assessment of pesticide toxicity in terrestrial amphibians.

PubMed

Fort, Douglas J; Mathis, Michael B; Kee, Faith; Whatling, Paul; Clerkin, David; Staveley, Jane; Habig, Clifford

2018-02-01

Development of an acute oral toxicity test with a terrestrial-phase amphibian was considered necessary to remove the uncertainty within the field of agrochemical risk assessments. The bullfrog (Lithobates catesbeianus) was selected for use as it is a representative of the family Ranidae and historically this species has been used as an amphibian test model species. Prior to definitive study, oral gavage methods were developed with fenthion and tetraethyl pyrophosphate. Dimethoate and malathion were subsequently tested with both male and female juvenile bullfrogs in comprehensive acute oral median lethal dose (LD50) studies. Juvenile bullfrogs were administered a single dose of the test article via oral gavage of a single gelatin capsule of dimethoate technical (dimethoate) or neat liquid Fyfanon ® Technical (synonym malathion), returned to their respective aquaria, and monitored for survival for 14 d. The primary endpoint was mortality, whereas behavioral responses, food consumption, body weight, and snout-vent length (SVL) were used to evaluate indications of sublethal toxicity (secondary endpoints). Acute oral LD50 values (95% fiducial interval) for dimethoate were 1459 (1176-1810, males) and 1528 (1275-1831, females), and for malathion they were 1829 (1480-2259, males) and 1672 (1280-2183, females) mg active substance/kg body weight, respectively. Based on the results of these studies, the methodology for the acute oral gavage administration of test items to terrestrial-phase amphibians was demonstrated as being a practical method of providing data for risk assessments. Environ Toxicol Chem 2018;37:436-450. © 2017 SETAC. © 2017 SETAC.

No increase in toxicity of pelvic irradiation when intensity modulation is employed: clinical and dosimetric data of 208 patients treated with post-prostatectomy radiotherapy.

PubMed

Jereczek-Fossa, Barbara A; Ciardo, Delia; Ferrario, Silvia; Fossati, Piero; Fanetti, Giuseppe; Zerini, Dario; Zannoni, Davide; Fodor, Cristiana; Gerardi, Marianna A; Surgo, Alessia; Muto, Matteo; Cambria, Raffaella; De Cobelli, Ottavio; Orecchia, Roberto

2016-07-01

To compare the toxicity of image-guided intensity-modulated radiotherapy (IG-IMRT) to the pelvis or prostate bed (PB) only. To test the hypothesis that the potentially injurious effect of pelvic irradiation can be counterbalanced by reduced irradiated normal tissue volume using IG-IMRT. Between February 2010 and February 2012, 208 patients with prostate cancer were treated with adjuvant or salvage IG-IMRT to the PB (102 patients, Group PB) or the pelvis and prostate bed (P) (106 patients, Group P). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria were used to evaluate toxicity. Median follow-up was 27 months. Toxicity G ≥ 2 in Group PB: in the bowel acute and late toxicities were 11.8% and 10%, respectively; urinary acute and late toxicities were 10.8% and 15%, respectively. Toxicity G ≥ 2 in Group P: in the bowel acute and late toxicities were both 13.2%; urinary acute and late toxicities were 13.2% and 15.1%, respectively. No statistical difference in acute or late toxicity between the groups was found (bowel: p = 0.23 and p = 0.89 for acute and late toxicity, respectively; urinary: p = 0.39 and p = 0.66 for acute and late toxicity, respectively). Of the clinical variables, only previous abdominal surgery was correlated with acute bowel toxicity. Dosimetric parameters that correlated with bowel toxicity were identified. The toxicity rates were low and similar in both groups, suggesting that IG-IMRT allows for a safe post-operative irradiation of larger volumes. Further investigation is warranted to exclude bias owing to non-randomized character of the study. Our report shows that modern radiotherapy technology and careful planning allow maintaining the toxicity of pelvic lymph node treatment at the acceptable level, as it is in the case of PB radiotherapy.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

PubMed Central

Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

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

EPA Science Inventory

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

Acute Toxicity of Tributyltins and Tributyltin Leachates from Marine Antibiofouling Paints.

DTIC Science & Technology

1982-09-10

RO-0184 224 ACUTE TOXICITY OF TRIBUTYLTINS AND TRIBUTYLTIN i/I LEACHATES FROM MARINE ANTIBIOFOULING PAINTS(U) CALIFORNIA UNIV OAKLAND NAVAL...Classification) (U) ACUTE TOXICITY OF TRIBUTYLTINS AND TRIBUTYLTIN LEACHATES FROM MARINE ANTIBIOFOULING PAINTS 12, PERSO A UHR Laugin, Koy"., Linden, Olof and...xins causing acute toxicity or two amphipou species at concentrations as low as 10 g/L . Orchestia traskiana was exposed to bis ( tributyltin ) oxide

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.

Burn unit care of Stevens Johnson syndrome/toxic epidermal necrolysis: A survey.

PubMed

Le, Hong-Gam; Saeed, Hajirah; Mantagos, Iason S; Mitchell, Caroline M; Goverman, Jeremy; Chodosh, James

2016-06-01

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a systemic disease that can be associated with debilitating acute and chronic complications across multiple organ systems. As patients with acute SJS/TEN are often treated in a burn intensive care unit (BICU), we surveyed burn centers across the United States to determine their approach to the care of these patients. The goal of our study was to identify best practices and possible variations in the care of patients with acute SJS/TEN. We demonstrate that the method of diagnosis, use of systemic therapies, and involvement of subspecialists varied significantly between burn centers. Beyond supportive care provided to every patient, our data highlights a lack of standardization in the acute care of patients with SJS/TEN. A comprehensive guideline for the care of patients with acute SJS/TEN is indicated. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

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

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneummore » plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.« less

Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

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

Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl; Terhaard, Chris H.; Doornaert, Patricia A.

2012-02-01

Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moistmore » desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.« less

Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

USGS Publications Warehouse

Vyas, Nimish B.; Rattner, Barnett A.

2012-01-01

Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

Deriving freshwater safety thresholds for hexabromocyclododecane and comparison of toxicity of brominated flame retardants.

PubMed

Dong, Liang; Zheng, Lei; Yang, Suwen; Yan, Zhenguang; Jin, Weidong; Yan, Yuhong

2017-05-01

Hexabromocyclododecane (HBCD) is a brominated flame retardant used throughout the world. It has been detected in various environmental media and has been shown toxic to aquatic life. The toxic effects of HBCD to aquatic organisms in Chinese freshwater ecosystems are discussed here. Experiments were conducted with nine types of acute toxicity testing and three types of chronic toxicity testing. After comparing a range of species sensitivity distribution models, the optimal model of Bull III was used to derive the safety thresholds for HBCD. The acute safety threshold and the chronic safety threshold of HBCD for Chinese freshwater organisms were found to be 2.32mg/L and 0.128mg/L, respectively. Both values were verified by the methods of the Netherlands and the United States. HBCD was found to be less toxic compared to other widely used brominated flame retardants. The present results provide valuable information for revision of the water quality standard of HBCD in China. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of Acute and Chronic Toxicity Trends of Pesticides Using High-Throughput Bioluminescence Assay Based on the Test Organism Vibrio fischeri.

PubMed

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

2018-05-01

High-throughput acute and chronic toxicity tests using Vibrio fischeri were used to assess the toxicity of a variety of fungicides, herbicides, and neonicotinoids. The use of time points beyond the traditional 30 min of an acute test highlighted the sensitivity and applicability of the chronic toxicity test and indicated that for some compounds toxicity is underestimated using only the acute test. The comparison of EC 50 values obtained from acute and chronic tests provided insight regarding the toxicity mode of action, either being direct or indirect. Using a structure-activity relationship approach similar to the one used in hazard assessments, the relationship between toxicity and key physicochemical properties of pesticides was investigated and trends were identified. This study not only provides new information regarding acute toxicity of some pesticides but also is one of the first studies to investigate the chronic toxicity of pesticides using the test organism V. fischeri. The findings demonstrated that the initial bioluminescence has a large effect on the calculated effective concentrations for target compounds in both acute and chronic tests, providing a way to improve and standardize the test protocol. In addition, the findings emphasize the need for additional investigation regarding the relationship between a toxicant's physicochemical properties and mode of action in nontarget organisms.

Antioxidant and Toxicity Studies of 50% Methanolic Extract of Orthosiphon stamineus Benth

PubMed Central

Lim, Chung Pin; Fung Ang, Lee; Por, Lip Yee; Wong, Siew Tung; Asmawi, Mohd. Zaini

2013-01-01

The present study evaluated the antioxidant activity and potential toxicity of 50% methanolic extract of Orthosiphon stamineus (Lamiaceae) leaves (MEOS) after acute and subchronic administration in rats. Superoxide radical scavenging, hydroxyl radical scavenging, and ferrous ion chelating methods were used to evaluate the antioxidant properties of the extract. In acute toxicity study, single dose of MEOS, 5000 mg/kg, was administered to rats by oral gavage, and the treated rats were monitored for 14 days. While in the subchronic toxicity study, MEOS was administered orally, at doses of 1250, 2500, and 5000 mg/kg/day for 28 days. From the results, MEOS showed good superoxide radical scavenging, hydroxyl radical scavenging, ferrous ion chelating, and antilipid peroxidation activities. There was no mortality detected or any signs of toxicity in acute and subchronic toxicity studies. Furthermore, there was no significant difference in bodyweight, relative organ weight, and haematological and biochemical parameters between both male and female treated rats in any doses tested. No abnormality of internal organs was observed between treatment and control groups. The oral lethal dose determined was more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of MEOS for both male and female rats is considered to be 5000 mg/kg per day. PMID:24490155

Use of statistical and neural net approaches in predicting toxicity of chemicals.

PubMed

Basak, S C; Grunwald, G D; Gute, B D; Balasubramanian, K; Opitz, D

2000-01-01

Hierarchical quantitative structure-activity relationships (H-QSAR) have been developed as a new approach in constructing models for estimating physicochemical, biomedicinal, and toxicological properties of interest. This approach uses increasingly more complex molecular descriptors in a graduated approach to model building. In this study, statistical and neural network methods have been applied to the development of H-QSAR models for estimating the acute aquatic toxicity (LC50) of 69 benzene derivatives to Pimephales promelas (fathead minnow). Topostructural, topochemical, geometrical, and quantum chemical indices were used as the four levels of the hierarchical method. It is clear from both the statistical and neural network models that topostructural indices alone cannot adequately model this set of congeneric chemicals. Not surprisingly, topochemical indices greatly increase the predictive power of both statistical and neural network models. Quantum chemical indices also add significantly to the modeling of this set of acute aquatic toxicity data.

77 FR 67771 - Flonicamid; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-14

... one of the following methods: Federal eRulemaking Portal: http://www.regulations.gov . Follow the... validity, completeness, and reliability as well as the relationship of the results of the studies to human... TFNA-OH, also demonstrated low toxicity in acute oral toxicity studies. In the 28-day dermal study with...

78 FR 36671 - Acetamiprid; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

... one of the following methods: Federal eRulemaking Portal: http://www.regulations.gov . Follow the... validity, completeness, and reliability as well as the relationship of the results of the studies to human... toxic in acute lethality studies via the oral route of exposure and is minimally toxic via the dermal...

Synthesis, DNA Cleavage Activity, Cytotoxicity, Acetylcholinesterase Inhibition, and Acute Murine Toxicity of Redox-Active Ruthenium(II) Polypyridyl Complexes.

PubMed

Alatrash, Nagham; Narh, Eugenia S; Yadav, Abhishek; Kim, Mahn-Jong; Janaratne, Thamara; Gabriel, James; MacDonnell, Frederick M

2017-07-06

Four mononuclear [(L-L) 2 Ru(tatpp)] 2+ and two dinuclear [(L-L) 2 Ru(tatpp)Ru(L-L) 2 ] 4+ ruthenium(II) polypyridyl complexes (RPCs) containing the 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) ligand were synthesized, in which L-L is a chelating diamine ligand such as 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me 4 phen) or 4,7-diphenyl-1,10-phenanthroline (Ph 2 phen). These Ru-tatpp analogues all undergo reduction reactions with modest reducing agents, such as glutathione (GSH), at pH 7. These, plus several structurally related but non-redox-active RPCs, were screened for DNA cleavage activity, cytotoxicity, acetylcholinesterase (AChE) inhibition, and acute mouse toxicity, and their activities were examined with respect to redox activity and lipophilicity. All of the redox-active RPCs show single-strand DNA cleavage in the presence of GSH, whereas none of the non-redox-active RPCs do. Low-micromolar cytotoxicity (IC 50 ) against malignant H358, CCL228, and MCF7 cultured cell lines was mainly restricted to the redox-active RPCs; however, they were substantially less toxic toward nonmalignant MCF10 cells. The IC 50 values for AChE inhibition in cell-free assays and the acute toxicity of RPCs in mice revealed that whereas most RPCs show potent inhibitory action against AChE (IC 50 values <15 μm), Ru-tatpp complexes as a class are surprisingly well tolerated in animals relative to other RPCs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles.

PubMed

Wei, Li; Shao, Wei-Wei; Ding, Guo-Hua; Fan, Xiao-Li; Yu, Miao-Ling; Lin, Zhi-Hua

2014-07-01

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas.

Hydrocarbons and surfactants: Ecotoxicology in a marine pelagic food chain

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

Skadsheim, A.; Hoivangli, V.; Labes-Carrier, C.

1996-12-31

Accidental spills and production lead to discharges of petroleum hydrocarbons and surface active agents to the sea. The Norwegian government has set guidelines adopted from the OSPAR commission for assessment and studies of the environmental load from these discharges. The free water masses are poorly studied compared to the benthic processes in this context and we question how oil and surfactants might bioaccumulate in a simplified marine pelagic food chain comprised of algae, crustaceans and fish. When test methods and species recommended for initial water based acute toxicity studies are to be implemented in more comprehensive studies like assessment ofmore » bioaccumulation various problems arose. An improvement of the OSPAR method for the production of Water Accommodated Fractions (WAFs) of oil is presented. Emphasis is on control of oil concentration and distribution in water, and on applicability for studies where larger volumes of WAF are required than for the demand in acute toxicity tests. Acute toxicity assessments of one oil, Blended Arabian Light topped at 150{degrees}C, and two non-ionic dispersants, hexaetoxyparanonylphenol and a sophorolipid, were conducted on OSPAR recommended species. The toxicity responses were in line with observations made by others. At a given concentration the oil particle size during WAF preparation might influence subsequent expression of toxic effects. The same applied for the presence of emulsified oil particles in the WAR where the organisms were exposed. Reasons for selecting other test organisms than those officially recommended for continued studies on bioaccumulation are presented and discussed.« less

Acute oral toxicity test of chemical compounds in silkworms.

PubMed

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

2016-02-01

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

Acute toxicity and primary irritancy of alkylalkanolamines.

PubMed

Ballantyne, B; Leung, H W

1996-12-01

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

Developmental Neurotoxicity of Pyrethroid Insecticides: Critical Review and Future Research Needs

PubMed Central

Shafer, Timothy J.; Meyer, Douglas A.; Crofton, Kevin M.

2005-01-01

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system. PMID:15687048

Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs.

PubMed

Shafer, Timothy J; Meyer, Douglas A; Crofton, Kevin M

2005-02-01

Pyrethroid insecticides have been used for more than 40 years and account for 25% of the worldwide insecticide market. Although their acute neurotoxicity to adults has been well characterized, information regarding the potential developmental neurotoxicity of this class of compounds is limited. There is a large age dependence to the acute toxicity of pyrethroids in which neonatal rats are at least an order of magnitude more sensitive than adults to two pyrethroids. There is no information on age-dependent toxicity for most pyrethroids. In the present review we examine the scientific data related to potential for age-dependent and developmental neurotoxicity of pyrethroids. As a basis for understanding this neurotoxicity, we discuss the heterogeneity and ontogeny of voltage-sensitive sodium channels, a primary neuronal target of pyrethroids. We also summarize 22 studies of the developmental neurotoxicity of pyrethroids and review the strengths and limitations of these studies. These studies examined numerous end points, with changes in motor activity and muscarinic acetylcholine receptor density the most common. Many of the developmental neurotoxicity studies suffer from inadequate study design, problematic statistical analyses, use of formulated products, and/or inadequate controls. These factors confound interpretation of results. To better understand the potential for developmental exposure to pyrethroids to cause neurotoxicity, additional, well-designed and well-executed developmental neurotoxicity studies are needed. These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system.

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.

Prediction of Solvent Physical Properties using the Hierarchical Clustering Method

EPA Science Inventory

Recently a QSAR (Quantitative Structure Activity Relationship) method, the hierarchical clustering method, was developed to estimate acute toxicity values for large, diverse datasets. This methodology has now been applied to the estimate solvent physical properties including sur...

Aquatic toxicity of petroleum products and dispersant agents ...

EPA Pesticide Factsheets

The U.S. EPA Office of Research and Development has developed baseline data on the ecotoxicity of selected petroleum products and several chemical dispersants as part of its oil spills research program. Two diluted bitumens (dilbits) from the Alberta Tar Sands were tested for acute and chronic toxicity to standard freshwater and marine organisms given their spill potential during shipment within the United States. Separately, two reference crude oils representing a range of characteristics, and their mixtures with four representative dispersants, were tested to evaluate acute and chronic toxicity to marine organisms in support of Subpart J of the U.S. National Contingency Plan. Water accommodated fractions (WAF) of oil were prepared using traditional slow-stir methods and toxicity tests generally followed U.S. EPA standard effluent testing guidelines. WAFs were characterized for petroleum hydrocarbons including alkyl PAH homologs. The results of these studies will assist the U.S. EPA to assess toxicity data for unconventional oils (dilbits), and establish baseline toxicity data for selected crude oils and dispersant in support of planning and response activities. Abstract reporting the results of EPA's oil and dispersant toxicity testing program

Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

USGS Publications Warehouse

Johnson, W. Waynon; Finley, Mack T.

1980-01-01

Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data from the Columbia Laboratory and its field laboratories. It presents definitive acute toxicity data on 271 chemicals tested against a variety of freshwater invertebrates and fishes. The chemicals represent all major groups of pesticides, as well as numerous industrial chemicals. This compilation should serve as a useful database for the many agencies and organizations dealing with research and management programs concerned with the impact of chemicals on aquatic resources.The Columbia Laboratory has played a major role in developing currently used standard methodology for static acute toxicity testing. The use of standardized methodology greatly reduces variation in results. The data presented here have been carefully scrutinized to eliminate tests that failed to follow acceptable procedures. Handling of test organisms and procedures for static toxicity tests followed those described by Lennon and Walker (1964) and Macek and McAllister (1970), and conform well with those recommended by Brauhn and Schoettger (1975) and the Committee on Methods for Toxicity Tests with Aquatic Organisms (1975).The species of fish and invertebrates that were tested are listed in phylogenetic order in Tables 1 and 2. Fish were obtained from Federal and State hatcheries as either eggs or fry. Original stocks of invertebrates were collected and cultured from wild populations with no known source of contamination; these populations were replenished regularly. The invertebrates were cultured in the Laboratory by methods similar to those described by Sanders and Cope (1966).Test chemicals usually consisted of technical or analytical grade samples of known purity. Formulations of the chemicals were also tested when available. When purity of test chemicals was known, all calculated concentrations were based on percent active ingredients. Stock solutions were prepared immediately before each test, with commercial grade acetone as the carrier solvent. Occasionally, ethanol or dimethyl-formamide was substituted. Solvent concentrations did not exceed 0.5 mL/L in final dilution water.Test water (dilution water) was reconstituted from deionized water of at least 106 ohms resistivity by the addition of appropriate reagent grade chemicals (Marking 1969). Water was buffered to maintain a pH of 7.2 to 7.5, an alkalinity of 30 to 35 mg/L, and a hardness of 40 to 50 mg/L as CaCO3. Test water was mixed thoroughly and aerated before transfer into test chambers. Fish were acclimated to dilution water by gradually changing the water in acclimated tanks from 100% well water to 100% reconstituted water over a 1- to 3-day period at the desired testing temperature. Invertebrates were acclimated from well water to dilution water over a 4- to 6-h period. Toxicity tests were conducted under static conditions without aeration, and the organisms were not fed during acclimation or testing. Temperature of test solutions was maintained within ± 1°C of that required for a given test.Toxicity tests with fish were conducted in 18.9-liter (5-gal) wide-mouthed jars containing 15 liters of test solution. Fingerling fish weighing 0.2 to 1.5 g were tested at each concentration. Caution was taken not to exceed 0.8 g of test organisms per liter of solution. Duplicate test chambers were used to accommodate larger fish. Test chambers varied in size for invertebrates, depending on the species used; volume of test solution ranged from 0.25 to 4 liters. At least 10 organisms were exposed to each concentration for all definitive tests. At least six concentrations were used per toxicity test.The tests began upon initial exposure to the toxicant and continued for 96 h. Immobilization tests with invertebrates were conducted for only 48 h. The number of dead or affected organisms in each test chamber were recorded and the dead organisms were removed every 24 h; general observations on the condition of test organisms were also recorded at these times.Toxicity data were analyzed by a statistical method described by Litchfield and Wilcoxon (1949) to determine LC50 (theoretical estimate of the concentration lethal to 50% of the test animals) and 95% confidence intervals. This method is recommended by the American Public Health Association (1971) and by Sprague (1969) for determining median lethal concentrations. The procedure is easily modified for computing a single LC50 when replicate tests are performed.

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

USGS Publications Warehouse

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

2017-01-01

The objectives of the present study were to develop methods for propagating western pearlshell (Margaritifera falcata) for laboratory toxicity testing and evaluate acute and chronic toxicity of chromium VI [Cr(VI)] to the pearlshell and a commonly tested mussel (fatmucket, Lampsilis siliquoidea at 20 °C or in association with a co-stressor of elevated temperature (27 °C), zinc (50 µg Zn/L), or nitrate (35 mg NO3/L). A commonly tested invertebrate (amphipod, Hyalella azteca) also was tested in chronic exposures. Newly transformed pearlshell (~1 week old) were successfully cultured and tested in acute 96 h Cr exposures (control survival 100%). However, the grow-out of juveniles in culture for chronic toxicity testing was less successful and chronic 28-day Cr toxicity tests started with 4 month-old pearlshell failed due to low control survival (39–68%). Acute median effect concentration (EC50) for the pearlshell (919 µg Cr/L) and fatmucket (456 µg Cr/L) tested at 20 °C without a co-stressor decreased by a factor of > 2 at elevated temperature but did not decrease at elevated Zn or elevated NO3. Chronic 28-day Cr tests were completed successfully with the fatmucket and amphipod (control survival 83–98%). Chronic maximum acceptable toxicant concentration (MATC) for fatmucket at 20 °C (26 µg Cr/L) decreased by a factor of 2 at elevated temperature or NO3 but did not decrease at elevated Zn. However, chronic MATC for amphipod at 20 °C (13 µg Cr/L) did not decrease at elevated temperature, Zn, or NO3. Acute EC50s for both mussels tested with or without a co-stressor were above the final acute value used to derive United States Environmental Protection Agency acute water quality criterion (WQC) for Cr(VI); however, chronic MATCs for fatmucket at elevated temperature or NO3 and chronic MATCs for the amphipod at 20 °C with or without elevated Zn or NO3 were about equal to the chronic WQC. The results indicate that (1) the elevated temperature increased the acute Cr toxicity to both mussel species, (2) fatmucket was acutely more sensitive to Cr than the pearlshell, (3) elevated temperature or NO3 increased chronic Cr toxicity to fatmucket, and (4) acute WQC are protective of tested mussels with or without a co-stressor; however, the chronic WQC might not protect fatmucket at elevated temperature or NO3 and might not protect the amphipod at 20 °C with or without elevated Zn or NO3.

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

The effect of olanzapine pretreatment on acute cocaine toxicity in mice.

PubMed

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

2009-07-01

Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

Acute And Subchronic Toxicity Studies Of SNEDDS (Self Nanoemulsifying Drug Delivery Systems) From Ethyl Acetate Extract Of Bay Leaf (Eugenia polyantha W.) with Virgin Coconut Oil As Oil Phase

NASA Astrophysics Data System (ADS)

Prihapsara, F.; Alamsyah, R. I.; Widiyani, T.; Artanti, A. N.

2018-03-01

Bay leaf (Eugenia polyantha) is widely used as an alternative therapy for diabetic and hypercholesterol. However, the administration of the extract has a low oral bioavailability, therefore it is prepared by Self Nanoemulsifying Drug Delivery Systems (SNEDDS) ethyl acetate extract of bay leaf. Therefore, acute and subchronic toxicity test is required. The toxicity test performed was an experimental study, including acute and subchronic toxicity tests. Animal experiments were used using Wistar strain rats. Acute toxicity test using 5 groups (n=5) consisted of 1 control group and 4 groups of SNEDDS dose with 48 mg/kgBW 240 mg/kg, 1200 mg/kg, and 6000 mg/kg, while for subchronic toxicity test with 1 group control and 3 groups of doses of SNEDDS with dose group variation 91.75 mg/kgBW, 183.5 mg/kg, and 367 mg/kg. Duration of observation at acute toxicity test for 14 days while for subcronic toxicity test for 28 days with continuous SNEDDS dosage. The results of the acute toxicity test showed toxic symptoms and obtained median lethal dose (LD50) values from SNEDDS from ethyl acetate extract of bay leaf 1409.30 mg/kgBW belonging to slightly toxic category. Subchronic toxicity studies show that the test drug has minor damage in liver and kidneys and moderate damage in pancreas.

PREDICTING CHRONIC LETHALITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: THEORY OF ACCELERATED LIFE TESTING

EPA Science Inventory

A method for modeling aquatic toxicity date based on the theory of accelerated life testing and a procedure for maximum likelihood fitting the proposed model is presented. he procedure is computerized as software, which can predict chronic lethality of chemicals using data from a...

A Novel Two-Step Hierarchial Quantitative Structure-Activity Relationship Modeling Workflow for Predicting Acute Toxicity of Chemicals in Rodents

EPA Science Inventory

Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database co...

Supercritical fluid chromatography-tandem mass spectrometry for the analysis of lipid A

USDA-ARS?s Scientific Manuscript database

Food safety and defense applications require the availability of methods of detection for a variety of toxic compounds in foods. One compound of concern is lipid A, an endotoxin from Gram-negative bacteria, which can cause human illness if it is present at acutely toxic levels in food. The chosen ...

Discriminating toxicant classes by mode of action. 1. (Eco)toxicity profiles.

PubMed

Nendza, Monika; Wenzel, Andrea

2006-05-01

Predictive toxicology, particularly quantitative structure-activity relationships (QSARs), require classification of chemicals by mode of action (MOA). MOA is, however, not a constant property of a compound but it varies between species and may change with concentration and duration of exposure. A battery of MOA-specific in-vitro and low-complexity assays, featuring biomolecular targets for major classes of environmental pollutants, provides characteristic responses for (1.) classification of chemicals by MOA, (2.) identification of (eco)toxicity profiles of chemicals, (3.) identification of chemicals with specific MOAs, (4.) indication of most sensitive species, (5.) identification of chemicals that are outliers in QSARs and (6.) selection of appropriate QSARs for predictions. Chemicals covering nine distinct modes of toxic action (non-polar non-specific toxicants (n=14), polar non-specific toxicants (n=18), uncouplers of oxidative phosphorylation (n=25), inhibitors of photosynthesis (n=15), inhibitors of acetylcholinesterase (n=14), inhibitors of respiration (n=3), thiol-alkylating agents (n=9), reactives (irritants) (n=8), estrogen receptor agonists (n=9)) were tested for cytotoxicity in the neutralred assay, oxygen consumption in isolated mitochondria, oxygen production in algae, inhibition of AChE, reaction with GSH and activity in the yeast estrogen receptor assay. Data on in-vivo aquatic toxicity (LC50, EC50) towards fish, daphnids, algae and bacteria were collected from the literature for reasons of comparison and reference scaling. In the MOA-specific in-vitro test battery, most test chemicals are specifically active at low concentrations, though multiple effects do occur. Graphical and statistical evaluation of the individual classes versus MOA 1 (non-polar non-specific toxicants) identifies interactions related to predominant MOA. Discriminant analyses (DA) on subsets of the data revealed correct classifications between 70% (in-vivo data) and >90% (in-vitro data). Functional similarity of chemical substances is defined in terms of their (eco)toxicity profiles. Within each MOA class, the compounds share some properties related to the rate-limiting interactions, e.g., steric fit to the target site and/or reactivity with target biomolecules, revealing a specific pattern (fingerprint) of characteristic effects. The successful discrimination of toxicant classes by MOA is based on comprehensive characterization of test chemicals' properties related to interactions with target sites. The suite of aquatic in-vivo tests using fish, daphnids, algae and bacteria covers most acute effects, whilst long-term (latent) impacts are generally neglected. With the MOA-specific in-vitro test battery such distinctions are futile, because it focuses on isolated targets, i.e. it indicates the possible targets of a chemical regardless of the timescale of effects. The data analysis indicates that the in-vitro battery covers most effects in vivo and moreover provides additional aspects of the compounds' MOA. Translating in-vitro effects to in-vivo toxicity requires combining physiological and chemical knowledge about underlying processes. Comparison of the specific in-vitro effects of a compound with the respective sensitivities of aquatic organisms indicates particularly sensitive species. Classifications of toxicants by MOA based on physicochemical descriptors provides insight to interactions and directs to mechanistic QSARs.

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

PubMed

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

2015-06-02

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

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.

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles

PubMed Central

WEI, Li; SHAO, Wei-Wei; DING, Guo-Hua; FAN, Xiao-Li; YU, Miao-Ling; LIN, Zhi-Hua

2014-01-01

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas. PMID:25017745

Analysis of Dosimetric Parameters Associated With Acute Gastrointestinal Toxicity and Upper Gastrointestinal Bleeding in Locally Advanced Pancreatic Cancer Patients Treated With Gemcitabine-Based Concurrent Chemoradiotherapy

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

Nakamura, Akira; Shibuya, Keiko, E-mail: kei@kuhp.kyoto-u.ac.jp; Matsuo, Yukinori

2012-10-01

Purpose: To identify the dosimetric parameters associated with gastrointestinal (GI) toxicity in patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based chemoradiotherapy. Methods and Materials: The data from 40 patients were analyzed retrospectively. Chemoradiotherapy consisted of conventional fractionated three-dimensional radiotherapy and weekly gemcitabine. Treatment-related acute GI toxicity and upper GI bleeding (UGB) were graded according to the Common Toxicity Criteria Adverse Events, version 4.0. The dosimetric parameters (mean dose, maximal absolute dose which covers 2 cm{sup 3} of the organ, and absolute volume receiving 10-50 Gy [V{sub 10-50}]) of the stomach, duodenum, small intestine, and a composite structure ofmore » the stomach and duodenum (StoDuo) were obtained. The planning target volume was also obtained. Univariate analyses were performed to identify the predictive factors for the risk of grade 2 or greater acute GI toxicity and grade 3 or greater UGB, respectively. Results: The median follow-up period was 15.7 months (range, 4-37). The actual incidence of acute GI toxicity was 33%. The estimated incidence of UGB at 1 year was 20%. Regarding acute GI toxicity, a V{sub 50} of {>=}16 cm{sup 3} of the stomach was the best predictor, and the actual incidence in patients with V{sub 50} <16 cm{sup 3} of the stomach vs. those with V{sub 50} of {>=}16 cm{sup 3} was 9% vs. 61%, respectively (p = 0.001). Regarding UGB, V{sub 50} of {>=}33 cm{sup 3} of the StoDuo was the best predictor, and the estimated incidence at 1 year in patients with V{sub 50} <33 cm{sup 3} of the StoDuo vs. those with V{sub 50} {>=}33 cm{sup 3} was 0% vs. 44%, respectively (p = 0.002). The dosimetric parameters correlated highly with one another. Conclusion: The irradiated absolute volume of the stomach and duodenum are important for the risk of acute GI toxicity and UGB. These results could be helpful in escalating the radiation doses using novel techniques, such as intensity-modulated radiotherapy, for the treatment of pancreatic cancer.« less

Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

PubMed

Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

2011-01-01

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

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

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

Ghilezan, Michel, E-mail: mghilezan@beaumont.edu; Martinez, Alvaro; Gustason, Gary

2012-07-01

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

Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats

PubMed Central

Collins, Gregory T.; Zaks, Matthew E.; Cunningham, Alyssa R.; St. Clair, Carley; Nichols, Joseph; Narasimhan, Diwahar; Ko, Mei-Chuan; Sunahara, Roger K.; Woods, James H.

2011-01-01

Background A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine’s cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine’s cardiovascular, convulsant, and lethal effects in male and female rats. Methods Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats. Results Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4 hrs, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity. Conclusions Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity. PMID:21481548

Do PCDD/PCDF standard solutions used in dioxin analysis pose a risk as potentially acutely toxic to lab personnel?

PubMed

Malisch, Rainer; Denison, Michael S; Fiedler, Heidelore; Fürst, Peter; Hoogenboom, Ron L A P; Schaechtele, Alexander; Schrenk, Dieter; van den Berg, Martin

2017-10-01

Laboratory safety requires protecting personnel from chemical exposures. Working with stock solutions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDFs) in routine analysis of feed and food with bioanalytical or physicochemical methods raises some concerns. Since PCDD/PCDFs are considered as possibly acutely toxic, the potential risks were evaluated to determine whether supervision of their use is necessary. Based on LD 50 -data for oral or dermal intake, hazard classification of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a substance (category 1) and in commercially available TCDD standard solutions (category 4) is different. As worst case exposure scenario during routine laboratory work it was assumed that a dose of 100 ng TCDD gets onto the skin and is absorbed. This would result in the total body burden of a 70 kg person with 15 kg fat increasing from 10 (upper range of current background levels) to ∼17 pg of toxic equivalents (TEQs) of PCDD/PCDFs per g lipid, a level commonly observed over past decades. Chloracne, the main acute effect occurring weeks after exposure, is observed at much higher blood concentrations than estimated from accidental laboratory exposure. Immunotoxicity, developmental effects and other toxic effects may occur at lower blood levels, but require longer periods to develop. Since acute toxic symptoms don't occur within an "8 h acute time window", no supervision is necessary when working with standard solutions in routine analysis. Nevertheless, precautionary measures are needed regarding long-term adverse health effects and appropriate workplace conditions must exist to ensure that additional occupational exposure to PCDD/PCDFs by laboratory personnel is negligible. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava

Introduction: Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). A large amount of biological substances or antigens isolated from bacterias (flagellin and derivates), plants, different types of venom (honeybees, scorpions, snakes) have been studied. This biological active substances can produce a nonspecific stimulation of immune system of mammals and protect against of mild doses of irradiation. But their radioprotection efficacy against high doses of radiation were not sufficient. Relative radioprotection characteristics or adaptive properties of antioxidants were expressed only at mild doses of radiation. However antioxidants demonstrated a very low protective efficacy at high doses of radiation. Some ex-periments demonstrated even a harmful effect of antioxidants administered to animals that had severe forms of the ARS. Only Specific Radiation Toxins roused a specific antigenic stim-ulation of antibody synthesis. An active immunization by non-toxic doses of radiation toxins includes a complex of radiation toxins that we call the Specific Radiation Determinant (SRD). Immunization must be provided not less than 24 days before irradiation and it is effective up to three years and more. Active immunization by radiation toxins significantly reduces the mortality rate (100%) and improves survival rate up to 60% compare with the 0% sur-vival rate among the irradiated animals in control groups. Material and Methods: The SRD molecules were isolated from Lymphatic Systems of animals that were irradiated with high doses of irradiation and had a clinical and laboratory picture of the Cerebral Acute Radia-tion Syndrome, Cardiovascular Acute Radiation Syndrome, Gastrointestinal Acute Radiation Syndrome, and Hematological Acute Radiation Syndrome. Our classification of radiation tox-ins includes 4 major groups: 1.SRD-1, Cerebrovascular neurotoxic Radiation Toxins (CvARS); 2.SRD-2, Cardiovascular Radiation Toxins(CrARS); 3.SRD-3,Gastrointestinal neurotoxic Ra-diation Toxins (GiARS); 4.SRD-4, Hematopietic Radiation Toxins (HpARS). Radiation tox-ins possess both toxic and immunological properties. But mechanisms of immune-toxicity by which radiation toxins stimulate development of the ARS are poorly understood. We have studied lethal toxicity of radiation toxins and an ability of specific antibodies to neutralize toxic activity of radiation toxins by specific antibodies. Results: The Blocking Antiradiation Antibodies induce an immunologically specific effect and inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity. Antiradiation Antibodies prevent the radiation induced cytolysis of selected groups of cells that are sensitive to radiation. The Blocking Antiradiation Antibodies are immunologically specific and can be produced by immunization with the different radiation toxins isolated from irradiated mam-mals. We propose that Specific Antiradiation Antibodies targeted against the radiation induced Toxins. Specific Antiradiation Antibodies neutralize toxic properties of radiation toxins. Anti-radiation Antibodies in different phases of the Acute Radiation Syndromes can compete with cytotoxic lymphocytes and prevent cytolysis mediated by cytotoxic lymphocytes. Conclusions: Immunological inhibition of cytotoxic and neurotoxic properties of Specific Radiation Toxins are significant factors for improving results of Medical Management of severe forms of the ARS and will optimize results of traditional methods of therapy of the ARS. Immunological inhi-bition of Radiation Toxins must be a part of technical procedure before haemotopoietic stem cells transplantation. Positive therapeutic results of neutralization of SRD RT could make a procedure of haemopoietic stem cell transplantation unnecessary.

20180311 - Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development (SOT)

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2012 CFR

2012-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

A comparative approach using ecotoxicological methods from single-species bioassays to model ecosystems.

PubMed

Haegerbaeumer, Arne; Höss, Sebastian; Ristau, Kai; Claus, Evelyn; Möhlenkamp, Christel; Heininger, Peter; Traunspurger, Walter

2016-12-01

Soft sediments are often hotspots of chemical contamination, and a thorough ecotoxicological assessment of this habitat can help to identify the causes of stress and to improve the health of the respective ecosystems. As an important component of the ecologically relevant meiobenthic fauna, nematodes can be used for sediment assessments, with various assay tools ranging from single-species toxicity tests to field studies. In the present study, microcosms containing sediment were used to investigate direct and indirect effects of zinc on natural nematode assemblages, and acute community toxicity tests considering only direct toxicity were conducted. The responses of the various freshwater nematode species in both approaches were compared with those of Caenorhabditis elegans, determined in standardized tests (ISO 10872). At a median lethal concentration (LC50) of 20 mg Zn/L, C. elegans represented the median susceptibility of 15 examined nematode species examined in the acute community toxicity tests. In the microcosms, Zn affected the nematodes dose-dependently, with changes in species composition first detected at 13 mg Zn/kg to 19 mg Zn/kg sediment dry weight. The observed species sensitivities in the microcosms corresponded better to field observations than to the results of the acute community toxicity tests. Environ Toxicol Chem 2016;35:2987-2997. © 2016 SETAC. © 2016 SETAC.

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

Dirix, Piet, E-mail: piet.dirix@uzleuven.b; Vanstraelen, Bianca; Jorissen, Mark

Purpose: To evaluate clinical outcome and toxicity of postoperative intensity-modulated radiotherapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between 2003 and 2008, 40 patients with cancer of the paranasal sinuses (n = 34) or nasal cavity (n = 6) received postoperative IMRT to a dose of 60 Gy (n = 21) or 66 Gy (n = 19). Treatment outcome and toxicity were retrospectively compared with that of a previous patient group (n = 41) who were also postoperatively treated to the same doses but with three-dimensional conformal radiotherapy without intensity modulation, from 1992 tomore » 2002. Results: Median follow-up was 30 months (range, 4-74 months). Two-year local control, overall survival, and disease-free survival were 76%, 89%, and 72%, respectively. Compared to the three-dimensional conformal radiotherapy treatment, IMRT resulted in significantly improved disease-free survival (60% vs. 72%; p = 0.02). No grade 3 or 4 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of acute as well as late side effects, especially regarding skin toxicity, mucositis, xerostomia, and dry-eye syndrome. Conclusions: Postoperative IMRT for sinonasal cancer significantly improves disease-free survival and reduces acute as well as late toxicity. Consequently, IMRT should be considered the standard treatment modality for malignancies of the nasal cavity and paranasal sinuses.« less

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

EPA Science Inventory

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

Evaluation of ability of reference toxicity tests to identify stress in laboratory populations of the amphipod Hyalella azteca

USGS Publications Warehouse

McNulty, E.W.; Dwyer, F.J.; Ellersieck, Mark R.; Greer, E.I.; Ingersoll, C.G.; Rabeni, C.F.

1999-01-01

Standard methods for conducting toxicity tests imply that the condition of test organisms can be established using reference toxicity tests. However, only a limited number of studies have evaluated whether reference toxicity tests can actually be used to determine if organisms are in good condition at the start of a test. We evaluated the ability of reference toxicants to identify stress associated with starvation in laboratory populations of the amphipod Hyalella azteca using acute toxicity tests and four reference toxicants: KCl, CdCl2, sodium pentachlorophenate (NaPCP), and carbaryl. Stress associated with severe starvation was observed with exposure of amphipods to carbaryl or NaPCP but not with exposure to KCl or CdCl2 (i.e., lower LC50 with severe starvation). Although the LC50s for NaPCP and carbaryl were statistically different between starved and fed amphipods, this difference may not be biologically significant given the variability expected in acute lethality tests. Stress associated with sieving, heat shock, or cold shock of amphipods before the start of a test was not evident with exposure to carbaryl or KCl as reference toxicants. The chemicals evaluated in this study provided minimal information about the condition of the organisms used to start a toxicity test. Laboratories should periodically perform reference toxicity tests to assess the sensitivity of life stages or strains of test organisms. However, use of other test acceptability criteria required in standard methods such as minimum survival, growth, or reproduction of organisms in the control treatment at the end of a test, provides more useful information about the condition of organisms used to start a test compared to data generated from reference toxicity tests.

Effects of water quality parameters on boron toxicity to Ceriodaphnia dubia.

PubMed

Dethloff, Gail M; Stubblefield, William A; Schlekat, Christian E

2009-07-01

The potential modifying effects of certain water quality parameters (e.g., hardness, alkalinity, pH) on the acute toxicity of boron were tested using a freshwater cladoceran, Ceriodaphnia dubia. By comparison, boron acute toxicity was less affected by water quality characteristics than some metals (e.g., copper and silver). Increases in alkalinity over the range tested did not alter toxicity. Increases in water hardness appeared to have an effect with very hard waters (>500 mg/L as CaCO(3)). Decreased pH had a limited influence on boron acute toxicity in laboratory waters. Increasing chloride concentration did not provide a protective effect. Boron acute toxicity was unaffected by sodium concentrations. Median acute lethal concentrations (LC(50)) in natural water samples collected from three field sites were all greater than in reconstituted laboratory waters that matched natural waters in all respects except for dissolved organic carbon. Water effect ratios in these waters ranged from 1.4 to 1.8. In subsequent studies using a commercially available source of natural organic matter, acute toxicity decreased with increased dissolved organic carbon, suggesting, along with the natural water studies, that dissolved organic carbon should be considered further as a modifier of boron toxicity in natural waters where it exceeds 2 mg/L.

75 FR 38417 - Carbaryl; Order Denying Washington Toxics Coalition Petition to Revoke Tolerances and Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-02

... uses on lawns and gardens, and indoors in kennels and on pet sleeping quarters. It was also registered...; cancellation of the following uses and application methods: all pet uses (dusts and liquids) except collars... carbaryl in pet collars, and environmental fate data. The product-specific DCI required acute toxicity and...

Acute toxicity and chemical evaluation of coking wastewater under biological and advanced physicochemical treatment processes.

PubMed

Dehua, Ma; Cong, Liu; Xiaobiao, Zhu; Rui, Liu; Lujun, Chen

2016-09-01

This study investigated the changes of toxic compounds in coking wastewater with biological treatment (anaerobic reactor, anoxic reactor and aerobic-membrane bioreactor, A1/A2/O-MBR) and advanced physicochemical treatment (Fenton oxidation and activated carbon adsorption) stages. As the biological treatment stages preceding, the inhibition effect of coking wastewater on the luminescence of Vibrio qinghaiensis sp. Nov. Q67 decreased. Toxic units (TU) of coking wastewater were removed by A1/A2/O-MBR treatment process, however approximately 30 % TU remained in the biologically treated effluent. There is a tendency that fewer and fewer residual organic compounds could exert equal acute toxicity during the biological treatment stages. Activated carbon adsorption further removed toxic pollutants of biologically treated effluent but the Fenton effluent increased acute toxicity. The composition of coking wastewater during the treatment was evaluated using the three-dimensional fluorescence spectra, gas chromatography-mass spectrometry (GC-MS). The organic compounds with high polarity were the main cause of acute toxicity in the coking wastewater. Aromatic protein-like matters in the coking wastewater with low biodegradability and high toxicity contributed mostly to the remaining acute toxicity of the biologically treated effluents. Chlorine generated from the oxidation process was responsible for the acute toxicity increase after Fenton oxidation. Therefore, the incorporation of appropriate advanced physicochemical treatment process, e.g., activated carbon adsorption, should be implemented following biological treatment processes to meet the stricter discharge standards and be safer to the environment.

Acute toxicity of ochratoxin-A in marine water-reared sea bass (Dicentrarchus labrax L.).

PubMed

El-Sayed, Yasser Said; Khalil, Riad Hassan; Saad, Talaat Talaat

2009-05-01

The toxic effects of ochratoxin-A (OTA) on sea bass, Dicentrarchus labrax L., have not been previously documented. A flow-through bioassay test system was conducted in two series and a total 180 of adult marine-reared sea bass was used to estimate the acute oral 96 h median lethal concentration (LC(50)) value and behavioral changes of OTA. The data obtained were statistically evaluated using Finney's Probit Analysis Method developed by EPA. The 96 h LC(50) value for adult D. labrax was found to be 277 microg kg(-1)bwt with 95% confidence limits of 244-311 microg kg(-1)bwt. This value was calculated to be 285 microg kg(-1) bwt with Behrens-Karber's method. The two methods were relatively comparable. The acute dietary 96 h LC(50) of OTA is 9.23 mg kg(-1) diet. Additionally, the behavioral changes of sea bass were primarily observed as nervous and respiratory manifestations. We concluded that sea bass is a species highly sensitive to OTA making them a useful experimental model for aquatic mycotoxigenic problems.

IDENTIFICATION AND EVALUATION OF STRESSORS IN TOXIC SEDIMENTS AND DREDGED MATERIALS

EPA Science Inventory

Identification of stressors in aquatic systems is critical to sound assessment and management of our nation's waterways for a number of reasons. Identification of specific classes of toxicants (or stressors) can be useful in designing effective sediment remediation methods and re...

Effect of olive mill wastewaters on the oxygen consumption by activated sludge microorganisms: an acute toxicity test method.

PubMed

Paixão, S M; Anselmo, A M

2002-01-01

The test for inhibition of oxygen consumption by activated sludge (ISO 8192-1986 (E)) was evaluated as a tool for assessing, the acute toxicity of olive mill wastewaters (OMW). According to the ISO test, information generated by this method may be helpful in estimating the effect of a test material on bacterial communities in the aquatic environment, especially in aerobic biological treatment systems. However, the lack of standardized bioassay methodology for effluents imposed that the test conditions were modified and adapted. The experiments were conducted in the presence or absence of an easily biodegradable carbon source (glucose) with different contact times (20 min and 24 h). The results obtained showed a remarkable stimulatory effect of this effluent to the activated sludge microorganisms. In fact, the oxygen uptake rate values increase with increasing effluent concentrations and contact times up to 0.98 microl O(2) h(-1) mg(-1) dry weight for a 100% OMW sample, 24 h contact time, with blanks exhibiting an oxygen uptake rate of ca. 1/10 of this value (0.07-0.10). It seems that the application of the ISO test as an acute toxicity test for effluents should be reconsidered, with convenient adaptation for its utilization as a method of estimating the effect on bacterial communities present in aerobic biological treatment systems. Copyright 2002 John Wiley & Sons, Ltd.

Image-guided total-marrow irradiation using helical tomotherapy in patients with multiple myeloma and acute leukemia undergoing hematopoietic cell transplantation.

PubMed

Wong, Jeffrey Y C; Rosenthal, Joseph; Liu, An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

2009-01-01

Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches.

Development of an acute oral toxicity dataset to facilitate assessment of existing QSARs and development of new models (WC10)

EPA Science Inventory

Acute oral toxicity data are used to meet both regulatory and non-regulatory needs. Recently, there have been efforts to explore alternative approaches for predicting acute oral toxicity such as QSARs. Evaluating the performance and scope of existing models and investigating the ...

Dose-Painted Intensity-Modulated Radiation Therapy for Anal Cancer: A Multi-Institutional Report of Acute Toxicity and Response to Therapy

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

Kachnic, Lisa A., E-mail: lisa.kachnic@bmc.org; Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; Tsai, Henry K.

2012-01-01

Purpose: Chemoradiation for anal cancer yields effective tumor control, but is associated with significant acute toxicity. We report our multi-institutional experience using dose-painted IMRT (DP-IMRT). Patients and Methods: Between August 2005 and May 2009, 43 patients were treated with DP-IMRT and concurrent chemotherapy for biopsy-proven, squamous cell carcinoma of the anal canal at two academic medical centers. DP-IMRT was prescribed as follows: T2N0: 42 Gy, 1.5 Gy/fraction (fx) to elective nodal planning target volume (PTV) and 50.4 Gy, 1.8 Gy/fx to anal tumor PTV; T3-4N0-3: 45 Gy, 1.5 Gy/fx to elective nodal PTV, and 54 Gy, 1.8 Gy/fx to themore » anal tumor and metastatic nodal PTV >3 cm with 50.4 Gy, 1.68 Gy/fx to nodal PTVs {<=}3 cm in size. Acute and late toxicity was reported by the treating physician. Actuarial analysis was performed using the Kaplan-Meier method. Results: Median age was 58 years; 67% female; 16% Stage I, 37% II; 42% III; 5% IV. Fourteen patients were immunocompromised: 21% HIV-positive and 12% on chronic immunosuppression. Median follow-up was 24 months (range, 0.6-43.5 months). Sixty percent completed chemoradiation without treatment interruption; median duration of treatment interruption was 2 days (range, 2-24 days). Acute Grade 3+ toxicity included: hematologic 51%, dermatologic 10%, gastrointestinal 7%, and genitourinary 7%. Two-year local control, overall survival, colostomy-free survival, and metastasis-free survival were 95%, 94%, 90%, and 92%, respectively. Conclusions: Dose-painted IMRT appears effective and well-tolerated as part of a chemoradiation therapy regimen for the treatment of anal canal cancer.« less

Development of small bisquaternary cholinesterase inhibitors as drugs for pre-treatment of nerve agent poisonings

PubMed Central

Kuca, Kamil; Karasova, Jana Zdarova; Soukup, Ondrej; Kassa, Jiri; Novotna, Eva; Sepsova, Vendula; Horova, Anna; Pejchal, Jaroslav; Hrabinova, Martina; Vodakova, Eva; Jun, Daniel; Nepovimova, Eugenie; Valis, Martin; Musilek, Kamil

2018-01-01

Background Intoxication by nerve agents could be prevented by using small acetylcholinesterase inhibitors (eg, pyridostigmine) for potentially exposed personnel. However, the serious side effects of currently used drugs led to research of novel potent molecules for prophylaxis of organophosphorus intoxication. Methods The molecular design, molecular docking, chemical synthesis, in vitro methods (enzyme inhibition, cytotoxicity, and nicotinic receptors modulation), and in vivo methods (acute toxicity and prophylactic effect) were used to study bispyridinium, bisquinolinium, bisisoquinolinium, and pyridinium-quinolinium/isoquinolinium molecules presented in this study. Results The studied molecules showed non-competitive inhibitory ability towards human acetylcholinesterase in vitro that was further confirmed by molecular modelling studies. Several compounds were selected for further studies. First, their cytotoxicity, nicotinic receptors modulation, and acute toxicity (lethal dose for 50% of laboratory animals [LD50]; mice and rats) were tested to evaluate their safety with promising results. Furthermore, their blood levels were measured to select the appropriate time for prophylactic administration. Finally, the protective ratio of selected compounds against soman-induced toxicity was determined when selected compounds were found similarly potent or only slightly better to standard pyridostigmine. Conclusion The presented small bisquaternary molecules did not show overall benefit in prophylaxis of soman-induced in vivo toxicity. PMID:29563775

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.

Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma

PubMed Central

Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

2018-01-01

Purpose This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. Materials and Methods HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62–92 GyE10. Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. Conclusion PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted. PMID:29580046

Radiation Dose-Volume Effects in the Stomach and Small Bowel

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

Kavanagh, Brian D., E-mail: Brian.Kavanagh@ucdenver.ed; Pan, Charlie C.; Dawson, Laura A.

2010-03-01

Published data suggest that the risk of moderately severe (>=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely relatedmore » to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.« less

In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae) Leaves.

PubMed

Fonseca, Aldilane Gonçalves; Ribeiro Dantas, Luzia Leiros Sena Fernandes; Fernandes, Júlia Morais; Zucolotto, Silvana Maria; Lima, Adley Antoninni Neves; Soares, Luiz Alberto Lira; Rocha, Hugo Alexandre Oliveira; Lemos, Telma Maria Araújo Moura

2018-01-01

The species Kalanchoe brasiliensis , known as "Saião , " has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis . The action of the extract (concentrations from 0.1 to 1000 uL/100 uL) in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal) and 786-0 (kidney carcinoma), showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo , the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential.

Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

PubMed Central

Ghadirkhomi, Akram; Safaeian, Leila; Zolfaghari, Behzad; Agha Ghazvini, Mohammad Reza; Rezaei, Parisa

2016-01-01

Objective: Pinus eldarica (P. eldarica) is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg) was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day) of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50) of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels. There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (p<0.05 and p<0.01, respectively) and in monocyte counts at the highest dose of the extract in both male and female rats (p<0.05). Mild inflammation was also found in histological examination of kidney and liver tissues at the highest dose of extract. Conclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg. PMID:27761426

Substance use, mental illness, and familial conflict non-negotiation among HIV-positive African-Americans: latent class regression and a new syndemic framework.

PubMed

Robinson, Allysha C; Knowlton, Amy R; Gielen, Andrea C; Gallo, Joseph J

2016-02-01

We evaluated a synergistic epidemic (syndemic) of substance use, mental illness, and familial conflict non-negotiation among HIV-positive injection drug users (IDU). Baseline BEACON study data was utilized. Latent class analyses identified syndemic classes. These classes were regressed on sex, viral suppression, and acute care non-utilization. Females were hypothesized to have higher syndemic burden, and worse health outcomes than males. Nine percent of participants had high substance use/mental illness prevalence (Class 4); 23 % had moderate levels of all factors (Class 3); 25 % had high mental illness (Class 2); 43 % had moderate substance use/mental illness (Class 1; N = 331). Compared to Classes 1-3, Class 4 was mostly female (p < .05), less likely to achieve viral suppression, and more likely to utilize acute care (p < .05). Interventions should target African-American IDU females to improve their risk of negative medical outcomes. Findings support comprehensive syndemic approaches to HIV interventions, rather than singular treatment methods.

Biomarker of Exposure and Mechanism of Action of Toxic Industrial Chemicals (TICs)

DTIC Science & Technology

2013-07-01

Quarterly Report for the period January 1, 2013-March 31, 2013. Using the sensitive and highly selective MRM approach described in that Quarterly...undetectable. This indicates that our LC-MS method is applicable to both high and low exposure levels. Second, the MRM method used on these samples is...toxicity of AN. First is that it can be metabolized in the body to cyanide, a well-known acute toxin. However, we have previously shown that

Kidney Transplant Rejection and Tissue Injury by Gene Profiling of Biopsies and Peripheral Blood Lymphocytes

PubMed Central

Flechner, Stuart M.; Kurian, Sunil M.; Head, Steven R.; Sharp, Starlette M.; Whisenant, Thomas C.; Zhang, Jie; Chismar, Jeffrey D.; Horvath, Steve; Mondala, Tony; Gilmartin, Timothy; Cook, Daniel J.; Kay, Steven A.; Walker, John R.; Salomon, Daniel R.

2007-01-01

A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients. PMID:15307835

Evaluation of processed borax as antidote for aconite poisoning.

PubMed

Sarkar, Prasanta Kumar; Prajapati, Pradeep K; Shukla, Vinay J; Ravishankar, Basavaiah

2017-06-09

Aconite root is very poisonous; causes cardiac arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is mentioned for management of aconite poisoning. The investigation evaluated antidotal effect of processed borax against acute and sub-acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw aconite. For acute protection Study, single dose of toxicant (35mg/kg) and test drug (22.5mg/kg and 112.5mg/kg) was administered orally, and then 24h survival of animals was observed. The schedule was continued for 30 days in sub-acute protection Study with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg and 112.5mg/kg) and vehicle. Hematological and biochemical tests of blood and serum, histopathology of vital organs were carried out. The cardiac activity Study was continued for 30 days with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg), processed borax solution (22.5mg/kg) and vehicle; ECG was taken after 1h of drug administration on 1 TB , 15th and on 30th day. For neuro-muscular activity Study, the leech dorsal muscle response to 2.5µg of acetylcholine followed by response of toxicant at 25µg and 50µg doses and then response of test drug at 25µg dose were recorded. Protection index indicates that treated borax gave protection to 50% rats exposed to the lethal dose of toxicant in acute protection Study. Most of the changes in hematological, biochemical parameters and histopathological Study induced by the toxicant in sub-acute protection Study were reversed significantly by the test drug treatment. The ventricular premature beat and ventricular tachyarrhythmia caused by the toxicant were reversed by the test drug indicate reversal of toxicant induced cardio-toxicity. The acetylcholine induced contractions in leech muscle were inhibited by toxicant and it was reversed by test drug treatment. The processed borax solution is found as an effective protective agent to acute and sub-acute aconite poisoning, and aconite induced cardiac and neuro-muscular toxicity. Processed borax at therapeutic dose (22.5mg/kg) has shown better antidotal activity profile than five times more than therapeutic dose (112.5mg/kg). Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

Soucek, David J; Dickinson, Amy

2015-09-01

Although insects occur in nearly all freshwater ecosystems, few sensitive insect models exist for use in determining the toxicity of contaminants. The objectives of the present study were to adapt previously developed culturing and toxicity testing methods for the mayfly Neocloeon triangulifer (Ephemeroptera: Baetidae), and to further develop a method for chronic toxicity tests spanning organism ages of less than 24 h post hatch to adult emergence, using a laboratory cultured diatom diet. The authors conducted 96-h fed acute tests and full-life chronic toxicity tests with sodium chloride, sodium nitrate, and sodium sulfate. The authors generated 96-h median lethal concentrations (LC50s) of 1062 mg Cl/L (mean of 3 tests), 179 mg N-NO3 /L, and 1227 mg SO4 /L. Acute to chronic ratios ranged from 2.1 to 6.4 for chloride, 2.5 to 5.1 for nitrate, and 2.3 to 8.5 for sulfate. The endpoints related to survival and development time were consistently the most sensitive in the tests. The chronic values generated for chloride were in the same range as those generated by others using natural foods. Furthermore, our weight-versus-fecundity plots were similar to those previously published using the food culturing method on which the present authors' method was based, indicating good potential for standardization. The authors believe that the continued use of this sensitive mayfly species in laboratory studies will help to close the gap in understanding between standard laboratory toxicity test results and field-based observations of community impairment. © 2015 SETAC.

Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight

NASA Technical Reports Server (NTRS)

Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael C.

2007-01-01

Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and functional conditions of impacted cells/organisms. The administration of an experimental anti-radiation vaccine may provide an immunologically based, adjunct method of prevention or prophylaxis against clinical ARS. The administration of experimental anti-radiation serum (ARS) and the use of the blood dialysis methods, such as immune plasma-sorption, may assist in the clearance of radiation-specific toxins and may enhance established strategies for the mitigation of the biological effects leading to ARS, and should be evaluated for use on exploration-class space missions.

77 FR 28340 - Revocation of TSCA Section 4 Testing Requirements for One High Production Volume Chemical Substance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-14

... a result, a biodegradation study of C.I. Pigment Blue 56, found adequate by an EPA review, satisfies the need for biodegradation data on C.I. Pigment Blue 61 (Ref. 5). Likewise, a fish acute toxicity..., water solubility, biodegradation, fish acute toxicity, mammalian acute toxicity, bacterial reverse...

CON4EI: CONsortium for in vitro Eye Irritation testing strategy - EpiOcular™ time-to-toxicity (EpiOcular ET-50) protocols for hazard identification and labelling of eye irritating chemicals.

PubMed

Kandarova, Helena; Letasiova, Silvia; Adriaens, Els; Guest, Robert; Willoughby, Jamin A; Drzewiecka, Agnieszka; Gruszka, Katarzyna; Alépée, Nathalie; Verstraelen, Sandra; Van Rompay, An R

2018-06-01

Assessment of acute eye irritation potential is part of the international regulatory requirements for testing of chemicals. The objective of the CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for eye irritation assessment for all drivers of classification. A set of 80 reference chemicals (38 liquids and 42 solids) was tested with eight different alternative methods. Here, the results obtained with reconstructed human cornea-like epithelium (RhCE) EpiOcular™ in the EpiOcular time-to-toxicity Tests (Neat and Dilution ET-50 protocols) are presented. The primary aim of this study was to evaluate whether test methods can discriminate chemicals not requiring classification for serious eye damage/eye irritancy (No Category) from chemicals requiring classification and labelling for Category 1 and Category 2. In addition, the predictive capacity in terms of in vivo drivers of classification was investigated. The chemicals were tested in two independent runs by MatTek In Vitro Life Science Laboratories. Results of this study demonstrate very high specificity of both test protocols. With the existing prediction models described in the SOPs, the specificity of the Neat and Dilution method was 87% and 100%, respectively. The Dilution method was able to correctly predicting 66% of GHS Cat 2 chemicals, however, prediction of GHS Cat 1 chemicals was only 47%-55% using the current protocols. In order to achieve optimal prediction for all three classes, a testing strategy was developed which combines the most predictive time-points of both protocols and for tests liquids and solids separately. Using this new testing strategy, the sensitivity for predicting GHS Cat 1 and GHS Cat 2 chemicals was 73% and 64%, respectively and the very high specificity of 97% was maintained. None of the Cat 1 chemicals was underpredicted as GHS No Category. Further combination of the EpiOcular time-to-toxicity protocols with other validated in vitro systems evaluated in this project, should enable significant reduction and even possible replacement of the animal tests for the final assessment of the irritation potential in all of the GHS classes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

PubMed

Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

2014-10-01

This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

Dosimetric and clinical predictors for radiation-induced esophageal injury.

PubMed

Ahn, Sung-Ja; Kahn, Daniel; Zhou, Sumin; Yu, Xiaoli; Hollis, Donna; Shafman, Timothy D; Marks, Lawrence B

2005-02-01

To evaluate the clinical and three-dimensional dosimetric parameters associated with esophageal injury after radiotherapy (RT) for non-small-cell lung cancer. The records of 254 patients treated for non-small-cell lung cancer between 1992 and 2001 were reviewed. A variety of metrics describing the esophageal dose were extracted. The Radiation Therapy Oncology Group toxicity criteria for grading of esophageal injury were used. The median follow-up time for all patients was 43 months (range, 0.5-120 months). Logistic regression analysis, contingency table analyses, and Fisher's exact tests were used for statistical analysis. Acute toxicity occurred in 199 (78%) of 254 patients. For acute toxicity of Grade 2 or worse, twice-daily RT, age, nodal stage of N2 or worse, and most dosimetric parameters were predictive. Late toxicity occurred in 17 (7%) of 238 patients. The median and maximal time to the onset of late toxicity was 5 and 40 months after RT, respectively. Late toxicity occurred in 2%, 3%, 17%, 26%, and 100% of patients with acute Grade 0, 1, 2, 3, and 4 toxicity, respectively. For late toxicity, the severity of acute toxicity was most predictive. A variety of dosimetric parameters are predictive of acute and late esophageal injury. A strong correlation between the dosimetric parameters prevented a comparison between the predictive abilities of these metrics. The presence of acute injury was the most predictive factor for the development of late injury. Additional studies to define better the predictors of RT-induced esophageal injury are needed.

Acute toxicity of chlorantraniliprole to non-target crayfish (Procambarus clarkii) associated with rice-crayfish cropping systems.

PubMed

Barbee, Gary C; McClain, W Ray; Lanka, Srinivas K; Stout, Michael J

2010-09-01

Chlorantraniliprole, a novel anthranilic diamide insecticide, was recently introduced into the United States where rice-crayfish crop rotations are practiced to control rice water weevil (Lissorhoptrus oryzophilus Kuschel) infestations. Chlorantraniliprole has high margins of mammalian safety and excellent insecticidal efficacy, but its toxicity to non-target crayfish is uncertain. In this study, the acute toxicity of chlorantraniliprole to the red swamp crayfish Procambarus clarkii Girard was determined using aquatic and feeding assays. The aquatic 96 h median lethal toxicity (LC(50)) data indicate that technical-grade chlorantraniliprole is highly toxic (US EPA category) to crayfish with an LC(50) of 951 microg L(-1) (95% CL = 741-1118 microg L(-1)). A no observed effect concentration (NOEC) of 480 microg L(-1) was recorded. Neither the 36 day chronic feeding study, where crayfish fed on chlorantraniliprole-treated rice seed in aquaria, nor the 144 h acute feeding test, where crayfish fed on rice seeds treated with chlorantraniliprole, produced mortality or abnormal behavior. Chlorantraniliprole is three orders of magnitude less acutely toxic to P. clarkii than lambda-cyhalothrin and etofenprox, two pyrethroid insecticides also used in rice, and is less likely to cause acute crayfish toxicity in rice pond ecosystems. Based on acute toxicity data, the use of chlorantraniliprole should be more compatible with rice-crayfish crop rotations than pyrethroids. (c) 2010 Society of Chemical Industry.

Temporal pattern of toxicity in runoff from the Tijuana River Watershed.

PubMed

Gersberg, Richard M; Daft, Daniel; Yorkey, Darryl

2004-02-01

Samples were collected from the Tijuana River under both dry weather (baseflow) conditions and during wet weather, and tested for toxicity using Ceriodaphnia dubia tests. Toxicity of waters in the Tijuana River was generally low under baseflow conditions, but increased markedly during high flow runoff events. In order to determine the temporal pattern of toxicity during individual rain events, sequential grab samples were collected using an autosampler at 5-7 h intervals after the start of the rain event, and tested for acute toxicity. In all cases, peak toxicity values (ranging from 2.8 to 5.8TU) for each storm occurred within the first 1-2 h of initiation of the rain event, and were statistically higher (using the 95% CL) for each of the pre-storm base flow values. However, there was no statistically significant correlation (p<0.05) between flow rate and toxicity when all storm data was pooled. Additionally, we used toxicity identification evaluation (TIE) procedures to attempt to identify the classes of chemicals that account for this early storm toxicity. Solid phase extraction was the only treatment that showed consistent and significant (P<0.05) removal of toxicity. These TIEs, conducted on the most toxic sample of the river's flow during runoff events, suggest that non-polar organics may be responsible for such toxicity. The temporal pattern of toxicity, both during a given storm event and seasonally, indicates that wash-off from the watershed by rainfall may deplete the supply of toxicity available for wash-off in subsequent events, so that a clearly consistent relationship between flow and toxicity was not evident.

Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

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

Dorn, Paige L., E-mail: pdorn@radonc.uchicago.edu; Corbin, Kimberly S.; Al-Hallaq, Hania

Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetricmore » parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women with a PTV volume >2,500 mL.« less

Toxicity hazard of organophosphate insecticide malathion identified by in vitro methods.

PubMed

Jira, David; Janousek, Stanislav; Pikula, Jiri; Vitula, Frantisek; Kejlova, Kristina

2012-01-01

Malathion is generally not classified as toxic. However, the toxicity seems to be species-dependent. Local and systemic toxicity data for birds are rare, but a decrease of wild bird densities in areas where malathion was applied was reported. Aim of the study was to extend knowledge on malathion toxicity on cellular and organ level and to evaluate embryotoxicity and genotoxicity for birds using the chick embryo model HET-CAM. Skin and eye irritation was determined using reconstructed skin and eye cornea tissues and the chorioallantoic membrane of chick embryo to simulate conjunctiva. Cytotoxicity in 3T3 Balb/c fibroblast culture was determined to estimate acute systemic toxicity. Chick embryo model was further employed to evaluate acute embryotoxicity for birds (mortality and genotoxicity). Data were analysed by means of general linear models. Malathion is not a skin and eye irritant. Cytotoxicity in vitro test provided LD50 value of 616 mg/kg suggesting higher toxic potential than is generally published based on in vivo tests on laboratory rodents. Embryotoxicity studies revealed dose and age dependent mortality of chick embryos. Genotoxicity was identified by means of micronucleus test in erythroid cells isolated from chorioallantois vascular system of chick embryos. Using in vitro alternative toxicological methods, a higher toxic potential of malathion was demonstrated than is generally declared. An increased health and environmental hazard may occur in areas with intensive agricultural production. The environmental consequences of delayed effects and embryotoxicity for bird populations in areas exposed to organophosphate insecticides, such as malathion, are obvious.

Toxicological evaluation of hydroethanolic extract of Helicteres sacarolha A. St.- Hil. et al.

PubMed

Balogun, Sikiru Olaitan; da Silva, Iberê Ferreira; Colodel, Edson Moleta; de Oliveira, Ruberlei Godinho; Ascêncio, Sérgio Donizeti; Martins, Domingos Tabajara de Oliveira

2014-11-18

Helicteres sacarolha, popularly known in Brazil as 'rosquinha', 'sacarolhas', 'semente-de-macaco', is widely distributed in different phytogeographic zones in Brazil. Preparations from its roots and leaves are employed in popular Brazilian medicine in the treatments of ailments such as peptic ulcer, hypertension among others. Cytotoxicity, acute oral and subchronic toxicity of the hydroethanolic extract of Helicteres sacrolha was investigated as well as the classes of phytochemical present in the extract. Hydroethanolic (70%) extract of Helicteres sacarolha (HEHs) was prepared by maceration. Potential cytotoxicity was evaluated in CHO-k1 cells. Acute administration of HEHs was done in mice as a single dose up to 5000mg/kg and subchronic oral toxicity study for 30 days in Wistar rats at daily oral doses of 0, 250 and 750mg/kg b.w. Clinical observations and toxicological related parameters were determined every 6 days. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Selected secondary metabolites detected were quantified by UV-spectrophotometry and high performance liquid chromatography (HPLC). The extract was non-cytotoxic to CHO-k1 cells. In acute oral toxicity, there was no mortality or clinical alterations in the female mice, at all doses, except for the transient diarrhea observed at 5000mg/kg acute. Doses up to 2000mg/kg caused no mortality or treatment-related clinical manifestations in the male mice, but treatment-related alterations were however observed at 4000mg/kg, with mortalities recorded at 5000mg/kg. During the subchronic oral toxicity study, no mortality or treatment-related clinical signs were observed. Differences in relative organ weight, hematological parameters and histopathology observations between the treated and the control groups were considered not to be treatment-related. Spectrophotometric analysis revealed the presence of relatively high content of phenolics and flavonoids in HEHs. HPLC analysis confirmed the presence of the quantified compounds and demonstrated the presence of ellagic acid, morin and naringin. Our results confirmed that HEHs have a broad safety margin for therapeutic use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Toxicopathological Evaluation of Hydroethanol Extract of Dianthus basuticus in Wistar Rats

PubMed Central

Ashafa, Anofi Omotayo Tom

2015-01-01

Background. Dianthus basuticus is a commonly used medicinal plant in Basotho traditional medicine for the treatment of diabetes, but there is no report on its safety or toxicity. Therefore, we evaluated the toxicity profile of the hydroethanol whole plant extract of Dianthus basuticus in Wistar rats. Methods. Acute toxicity test was performed with single oral administration of 100–3200 mg/kg body weight of D. basuticus extract to rats and the animals were observed for 14 days for signs of toxicity. The subacute toxicity experiment was conducted by oral administration of graded doses (200, 400, and 800 mg/kg) of D. basuticus extract daily for 28 days. Behavioural changes as well as haematological, biochemical, and histological parameters were then evaluated. Results. There was no observable sign of toxicity in the acute toxicity test. There were significant decreases (P < 0.05) in the feed and water intake as well as total cholesterol and triglycerides of the D. basuticus extract-treated rats in subacute toxicity study. There were no treatment related differences in the haematological, biochemical, and histopathological evaluations. Conclusions. Administration of hydroethanol extract of D. basuticus may be safe at the dosages tested in this study but its continuous usage can cause anorexia. PMID:26504473

Acute toxicity of some nerve agents and pesticides in rats.

PubMed

Misik, Jan; Pavlikova, Ruzena; Cabal, Jiri; Kuca, Kamil

2015-01-01

Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure. V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/). The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.

Acute poisoning in a child following topical treatment of head lice (pediculosis capitis) with an organophosphate pesticide.

PubMed

Hamad, Muddathir H; Adeel, Ahmed Awad; Alhaboob, Ali Abdu N; Ashri, Ahmed M; Salih, Mustafa A

2016-01-01

This is a case report of acute organophosphate poisoning in a child treated with topical application of Diazinon-60 (WHO Class II toxicity) for head lice (pediculosis capitis). The patient presented with neurological symptoms and signs. After emergency respiratory and circulatory resuscitation the patient underwent dermal decontamination and was treated with atropine, high flow oxygen and pralidoxime. Scanning electron micrographs of scalp hair specimens revealed both viable and empty head lice nits (lice eggs that attach to the hair shaft). The patient was hospitalized for seven days and discharged after full recovery. The case highlights the importance of raising the awareness of health workers and the community about the danger of misusing pesticides for the treatment of head lice.

Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer

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

Lewis, Stephen L.; Patel, Pretesh; Song, Haijun

2016-03-01

Purpose: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. Methods and Materials: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities weremore » scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. Results: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre-RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade ≥3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). Conclusions: The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved.« less

SEDIMENT TOXICITY IDENTIFICATION AND EVALUATIONS: NEW TEST METHODS. WHAT'S BEEN DONE? WHERE ARE WE GOING?

EPA Science Inventory

Toxic sediments pose a risk to aquatic life, human health and wildlife throughout the world. There is an overwhelming amount of evidence that demonstrates chemicals in sediments are responsible for toxicological and ecological effects. The ability to identify the class or specifi...

Acute Oral Toxicity Up-And-Down-Procedure

EPA Pesticide Factsheets

The Up-and-Down Procedure is an alternative acute toxicity test that provides a way to determine the toxicity of chemicals with fewer test animals by using sequential dosing steps. Find out about this test procedure.

PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: CONCEPT AND LINEAR REGRESSION

EPA Science Inventory

A comprehensive approach to predicting chronic toxicity from acute.toxicity data was developed in which simultaneous consideration is given to concentration, degree of response, and time course of effect. onsistent endpoint (lethality) and degree of response (O%) were used to com...

Health effects research in direct coal liquefaction. Studies of H-coal distillates: Phase I. PDU samples - the effects of hydrotreatment

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

Epler, J.L.; Fry, R.J.M.; Larimer, F.W.

1981-11-01

A multi-divisional effort aimed at the integrated assessment of the health and environmental effects of various coal conversion and shale oil technologies is being carried out. The feasibility of using health effects bioassays to predict the potential biohazard of various H-Coal derived test materials is examined in a coupled chemical and biological approach. The primary focus of the research is the use of preliminary chemical characterizations and preparation for bioassay, followed by testing in short-term assays in order to rapidly ascertain the potential biohazard. Mammalian toxicological assays parallel the testing. Raw and hydrotreated product liquids from process development units ofmore » H-Coal and the pilot plant solvent refined coal process were examined for acute toxicity monitored as population growth impairment of Tetrahymena exposed to aqueous extracts and for mutagenic activity monitored as revertants of Salmonella exposed to metabolically activated chemical class fractions. Medium to high severity hydrotreatment appears to be an effective means of reducing biological activity, presumably by reducing the aromaticity and heteroatom content. Five basic mammalian, acute toxicity tests have been conducted with selected H-coal samples and shale oil derivatives. The data show that H-Coal samples are moderately toxic whereas the toxicity of shale oil derived products is slight and comparable to samples obtained from naturally occurring petroleums. No overt skin or eye toxicity was found. The present data reveal that coal-derived distillates generated by the H-coal process are highly carcinogenic to mouse skin. An extreme form of neurotoxicity associated with dermal exposure to one of the lighter, minimally carcinogenic, materials was noted. (DMC)« less

Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

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

Deville, Curtiland, E-mail: deville@uphs.upenn.edu; Vapiwala, Neha; Hwang, Wei-Ting

2012-03-15

Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluatedmore » uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.« less

Diffusive Milli-Gels (DMG) for in situ assessment of metal bioavailability: A comparison with labile metal measurement using Chelex columns and acute toxicity to Ceriodaphnia dubia for copper in freshwaters.

PubMed

Perez, Magali; Simpson, Stuart L; Lespes, Gaëtane; King, Josh J; Adams, Merrin S; Jarolimek, Chad V; Grassl, Bruno; Schaumlöffel, Dirk

2016-12-01

Fluctuations in concentrations of bioavailable metals occur in most natural waters. In situ measurements are desirable to predict risks of adverse effects to aquatic organisms. We evaluated Diffusive Milli-Gels (DMG), a new in situ passive sampler, for assessing the bioavailability and toxicity of copper in waters exhibiting a wide range of characteristics. The performance was compared to an established Chelex-column method that measures labile copper concentrations by discrete sampling, and the ability to predict acute toxicity to the cladoceran, Ceriodaphnia dubia. The labile copper concentrations measured by the DMG and Chelex-column methods decreased with increasing dissolved organic carbon (DOC) (1.9-15 mg L -1 ) and hardness (21-270 mg CaCO 3  L -1 hardness), with 20-70% of total dissolved copper being present as labile copper. Toxicity decreased with increasing DOC and hardness. Strong linear relationships existed between the EC50 for C. dubia and DOC, and when the EC50 was related to either the labile copper concentrations measured by DMG (r 2  = 0.874) or the Chelex column (0.956) methods. The study demonstrates that the DMG passive sampler is a relevant tool for the in situ assessment of environmental risks posed by metals whose toxicity is strongly influenced by speciation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Change in the quantity and acute toxicity of pesticides sold in South African crop sectors, 1994 –1999

PubMed Central

Africa, Algernon; London, Leslie

2009-01-01

BACKGROUND South African pesticide market sales data, for two years, 1994 and 1999, were audited to identify change in total and per hectare mass sold and acute toxicity indicator (ATI) (kg sold/rat oral LD50) in the grape, pome, stone fruit, potato and wheat sectors. RESULTS Total pesticide sales (62%), amount per hectare (42%) and number of active ingredients (23%) increased in 1999 compared to 1994 with the grape fruit sector, the most significant contributor over the two years. Total (14%) and per hectare ATI (19%) decreased in 1999, but not substantially with the potato sector the most significant contributor. CONCLUSIONS Toxic pesticides were still used in 1999 which highlights a need to develop alternative agricultural and non-chemical pest control methods that reduce usage of pesticides. PMID:19185919

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Acute Toxicity to Daphnia: ASTM E 729 3. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the... conditions. Test Group 1 for C2: 1. Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM...

40 CFR 799.5085 - Chemical testing requirements for first group of high production volume chemicals (HPV1).

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Acute Toxicity to Daphnia: ASTM E 729 3. Toxicity to Plants (Algae): ASTM E 1218 Test Group 2 for C1: 1. Chronic Toxicity to Daphnia: ASTM E 1193 2. Toxicity to Plants (Algae): ASTM E 1218 The following are the... conditions. Test Group 1 for C2: 1. Acute Toxicity to Daphnia: ASTM E 729 2. Toxicity to Plants (Algae): ASTM...

KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia.

PubMed

Etchin, Julia; Sanda, Takaomi; Mansour, Marc R; Kentsis, Alex; Montero, Joan; Le, Bonnie T; Christie, Amanda L; McCauley, Dilara; Rodig, Scott J; Kauffman, Michael; Shacham, Sharon; Stone, Richard; Letai, Anthony; Kung, Andrew L; Thomas Look, A

2013-04-01

This study explored the anti-leukaemic efficacy of novel irreversible inhibitors of the major nuclear export receptor, chromosome region maintenance 1 (CRM1, also termed XPO1). We found that these novel CRM1 antagonists, termed SINE (Selective Inhibitors of Nuclear Export), induced rapid apoptosis at low nanomolar concentrations in a panel of 14 human T-cell acute lymphoblastic leukaemia (T-ALL) cell lines representing different molecular subtypes of the disease. To assess in vivo anti-leukaemia cell activity, we engrafted immunodeficient mice intravenously with the human T-ALL MOLT-4 cells, which harbour activating mutations of NOTCH1 and NRAS as well as loss of function of the CDKN2A, PTEN and TP53 tumour suppressors and express a high level of oncogenic transcription factor TAL1. Importantly, we examined the in vivo anti-leukaemic efficacy of the clinical SINE compound KPT-330 against T-ALL and acute myeloid leukaemia (AML) cells. These studies demonstrated striking in vivo activity of KPT-330 against T-ALL and AML cells, with little toxicity to normal murine haematopoietic cells. Taken together, our results show that SINE CRM1 antagonists represent promising 'first-in-class' drugs with a novel mechanism of action and wide therapeutic index, and imply that drugs of this class show promise for the targeted therapy of T-ALL and AML. © 2013 Blackwell Publishing Ltd.

Using ultrahigh-resolution mass spectrometry and toxicity identification techniques to characterize the toxicity of oil sands process-affected water: The case for classical naphthenic acids.

PubMed

Hughes, Sarah A; Mahaffey, Ashley; Shore, Bryon; Baker, Josh; Kilgour, Bruce; Brown, Christine; Peru, Kerry M; Headley, John V; Bailey, Howard C

2017-11-01

Previous assessments of oil sands process-affected water (OSPW) toxicity were hampered by lack of high-resolution analytical analysis, use of nonstandard toxicity methods, and variability between OSPW samples. We integrated ultrahigh-resolution mass spectrometry with a toxicity identification evaluation (TIE) approach to quantitatively identify the primary cause of acute toxicity of OSPW to rainbow trout (Oncorhynchus mykiss). The initial characterization of OSPW toxicity indicated that toxicity was associated with nonpolar organic compounds, and toxicant(s) were further isolated within a range of discrete methanol fractions that were then subjected to Orbitrap mass spectrometry to evaluate the contribution of naphthenic acid fraction compounds to toxicity. The results showed that toxicity was attributable to classical naphthenic acids, with the potency of individual compounds increasing as a function of carbon number. Notably, the mass of classical naphthenic acids present in OSPW was dominated by carbon numbers ≤16; however, toxicity was largely a function of classical naphthenic acids with ≥17 carbons. Additional experiments found that acute toxicity of the organic fraction was similar when tested at conductivities of 400 and 1800 μmhos/cm and that rainbow trout fry were more sensitive to the organic fraction than larval fathead minnows (Pimephales promelas). Collectively, the results will aid in developing treatment goals and targets for removal of OSPW toxicity in water return scenarios both during operations and on mine closure. Environ Toxicol Chem 2017;36:3148-3157. © 2017 SETAC. © 2017 SETAC.

Zebrafish (Danio rerio) Models To Assess Acute, Developmental, And Neurodevelopmental Toxicity

EPA Science Inventory

Zebrafish (Danio rerio) acute, developmental, and neurodevelopmental model systems have been developed to assess both known and unknown environmental contaminants. Developmental toxicity is assessed using death and dysmorphology as endpoints, whereas neurodevelopmental toxicity ...

Philadelphia chromosome negative B-cell acute lymphoblastic leukemia in older adults: Current treatment and novel therapies.

PubMed

O'Dwyer, Kristen M; Liesveld, Jane L

2017-09-01

Older adults with Philadelphia chromosome negative (Ph-),-B-cell acute lymphoblastic leukemia (ALL) have the highest rates of treatment failure and treatment complications with current therapy, and, thus, there is no standard treatment for these patients. Approximately 16 percent of patients with newly diagnosed Ph- B-cell ALL are aged 60 years or older [1]. The five-year overall survival for this older cohort of patients is approximately 20 percent, and there has been no improvement in their survival in decades [2]. The challenge in managing older patients with ALL is achieving balance between efficacy of treatment and the toxicity of multi-agent chemotherapy. The latter approach is highly effective in younger adults, but greatly limited by toxicity in older adults. New classes of agents, bi-specific T-cell engager (BiTE) monoclonal antibody and antibody drug conjugates (ADC) have been introduced into the treatment of ALL, and these agents have achieved therapeutic responses and manageable toxicity in patients of all ages with relapsed refractory ALL. These newer immunotherapy agents may improve the treatment of older adults. This review focuses on the new approaches to treatment of Ph- B-cell ALL in older patients. Other reviews in this special edition of ALL will focus on Philadelphia chromosome positive ALL, Philadelphia-like ALL, and allogeneic stem cell transplant as related to older adults. Copyright © 2017. Published by Elsevier Ltd.

The effect of tramadol hydrochloride on early life stages of fish.

PubMed

Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Berankova, Petra; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Vecerek, Vladimir; Svobodova, Zdenka

2016-06-01

The aim of this study was to perform the fish embryo acute toxicity test (FET) on zebrafish (Danio rerio) and the early-life stage toxicity test on common carp (Cyprinus carpio) with tramadol hydrochloride. The FET was performed using the method inspired by the OECD guideline 236. Newly fertilized zebrafish eggs were exposed to tramadol hydrochloride at concentrations of 10; 50; 100 and 200μg/l for a period of 144h. An embryo-larval toxicity test on C. carpio was performed according to OECD guideline 210 also with tramadol hydrochloride at concentrations 10; 50; 100 and 200μg/l for a period of 32 days. Hatching was significantly influenced in both acute and subchronic toxicity assays. Subchronic exposure also influenced early ontogeny, both morphometric and condition characteristics and caused changes in antioxidant enzyme activity. The LOEC value was found to be 10μg/l tramadol hydrochloride. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment complications after sequential combination chemotherapy and radiotherapy with or without surgery in previously untreated squamous cell carcinoma of the head and neck

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

Posner, M.R.; Weichselbaum, R.R.; Fitzgerald, T.J.

1985-11-01

One hundred consecutive patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with induction combination chemotherapy followed by definitive surgery and/or radiotherapy, and were evaluated for radiotherapy related toxicity. The induction regimen consisted of cisplatin, bleomycin and methotrexate/leucovorin. Acute toxicity consisted predominantly of mucositis and weight loss, and was mild or moderate by degree in 94% of patients. Six percent of patients experienced severe or life threatening acute toxicities. Two acute toxic deaths were noted in this series, one from a combination of mucositis, weight loss and infection and one from hypoglycemia of unknownmore » origin. Thirty-five percent of patients had radiation treatment interrupted briefly because of acute toxicity. Radiotherapy dose, surgical intervention and age did not have an impact on the presence or degree of acute toxicity. Late toxicities included: hypothyroidism in 32% of patients tested: osteoradionecrosis in 5% of patients, associated primarily with a composite resection (4 of 5 cases); and soft tissue ulcerations in 3%. Taken together, these data indicate that induction combination chemotherapy did not significantly increase the toxicity of subsequent radiotherapy with or without surgery.« less

Chemoradiation related acute morbidity in carcinoma cervix and correlation with hematologic toxicity: a South Indian prospective study.

PubMed

Kumaran, Aswathy; Guruvare, Shyamala; Sharan, Krishna; Rai, Lavanya; Hebbar, Shripad

2014-01-01

To assess chemoradiation related acute morbidity in women with carcinoma cervix and to find and correlation between hematologic toxicity and organ system specific damage. A prospective study was carried out between August 2012 and July 2013 enrolling 79 women with cancer cervix receiving chemo-radiotherapy. Weekly assessment of acute morbidity was done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 and the toxicities were graded. Anemia [77 (97.5%)], vomiting [75 (94.8%)] and diarrhea [72 (91.1%)], leukopenia [11 (13.9%)], cystitis [28 (35.4%], dermatitis [19 (24.1%)] and fatigue [29 (36.71%)] were the acute toxicities noted. The toxicities were most severe in 3rd and 5th week. All women could complete radiotherapy except two due to causes unrelated to radiation morbidity; seven (8.86%) had to discontinue chemotherapy due to leukopenia and intractable diarrhea. Though there was no correlation between anemia and other toxicities, it was found that all with leukopenia had diarrhea. Chemoradiation for cancer cervix is on the whole well tolerated. Leukopenia and severe diarrhea were the acute toxicities that compelled discontinuation of chemotherapy in two women. Though anemia had no correlation with gastrointestinal toxicity, all of those with leukopenia had diarrhea.

Acute and Subacute Toxicity of Safranal, a Constituent of Saffron, in Mice and Rats

PubMed Central

Hosseinzadeh, Hossein; Sadeghi Shakib, Saied; Khadem Sameni, Abbas; Taghiabadi, Elahe

2013-01-01

The acute and sub-acute toxicity of safranal were studied in rat and mice within 2 and 21 days after exposure, respectively. For subacute toxicity, changes in weight as well as biochemical, hematological and pathological parameters were studied. The intraperitoneal LD50 values of safranal were 1.48 mL/kg in male mice, 1.88 mL/kg in female mice and 1.50 mL/kg in male rats. Oral LD50 values were 21.42 mL/kg in male mice, 11.42 mL/kg in female mice and 5.53 mL/kg in male rats. For subacute toxicity, safranal was administered orally to male rats once daily for 21 days. In hematological tests, a significant decrease in RBC counts, hematocrit, hemoglobin and platelets were observed. Safranal decreased cholesterol, triglyceride and alkalin phosphatase. Lactate dehydrogenase and serum urea nitrogen were increased by safranal. Histological studies indicated that safranal did not have any toxic effect on the heart, liver and spleen. However, pathological changes were seen in the kidney and lung. According to LD50 values, safranal was low-toxic in acute intraperitoneal route and practically non-toxic in acute oral administration in both mice and rats. In subacute toxicity, safranal changed some hematological and biochemical parameters. PMID:24250576

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

PubMed Central

2014-01-01

Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route. PMID:24684892

Prospective Evaluation of Acute Toxicity and Quality of Life After IMRT and Concurrent Chemotherapy for Anal Canal and Perianal Cancer

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

Han, Kathy; Cummings, Bernard J.; Lindsay, Patricia

Purpose: A prospective cohort study was conducted to evaluate toxicity, quality of life (QOL), and clinical outcomes in patients treated with intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for anal and perianal cancer. Methods and Materials: From June 2008 to November 2010, patients with anal or perianal cancer treated with IMRT were eligible. Radiation dose was 27 Gy in 15 fractions to 36 Gy in 20 fractions for elective targets and 45 Gy in 25 fractions to 63 Gy in 35 fractions for gross targets using standardized, institutional guidelines, with no planned treatment breaks. The chemotherapy regimen was 5-fluorouracil and mitomycin C. Toxicitymore » was graded with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and CR29 questionnaires. Correlations between dosimetric parameters and both physician-graded toxicities and patient-reported outcomes were evaluated by polyserial correlation. Results: Fifty-eight patients were enrolled. The median follow-up time was 34 months; the median age was 56 years; 52% of patients were female; and 19% were human immunodeficiency virus—positive. Stage I, II, III, and IV disease was found in 9%, 57%, 26%, and 9% of patients, respectively. Twenty-six patients (45%) required a treatment break because of acute toxicity, mainly dermatitis (23/26). Acute grade 3 + toxicities included skin 46%, hematologic 38%, gastrointestinal 9%, and genitourinary 0. The 2-year overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS), and cumulative locoregional failure (LRF) rates were 90%, 77%, 84%, and 16%, respectively. The global QOL/health status, skin, defecation, and pain scores were significantly worse at the end of treatment than at baseline, but they returned to baseline 3 months after treatment. Social functioning and appetite scores were significantly better at 12 months than at baseline. Multiple dose-volume parameters correlated moderately with diarrhea, skin, and hematologic toxicity scores. Conclusion: IMRT reduces acute grade 3 + hematologic and gastrointestinal toxicities compared with reports from non-IMRT series, without compromising locoregional control. The reported QOL scores most relevant to acute toxicities returned to baseline by 3 months after treatment.« less

Pesticide Use and Self-Reported Symptoms of Acute Pesticide Poisoning among Aquatic Farmers in Phnom Penh, Cambodia.

PubMed

Jensen, Hanne Klith; Konradsen, Flemming; Jørs, Erik; Petersen, Jørgen Holm; Dalsgaard, Anders

2011-01-01

Organophosphates and carbamates (OPs/CMs) are known for their acetylcholinesterase inhibiting character. A cross-sectional study of pesticide handling practices and self-perceived symptoms of acute pesticide poisoning was conducted using questionnaire-based interviews with 89 pesticide sprayers in Boeung Cheung Ek (BCE) Lake, Phnom Penh, Cambodia. The study showed that 50% of the pesticides used belonged to WHO class I + II and personal protection among the farmers were inadequate. A majority of the farmers (88%) had experienced symptoms of acute pesticide poisoning, and this was significantly associated with the number of hours spent spraying with OPs/CMs (OR = 1.14, CI 95%: 1.02-1.28). The higher educated farmers reduced their risk of poisoning by 55% for each extra personal protective measure they adapted (OR = 0.45, CI 95%: 0.22-0.91). These findings suggest that improving safe pesticide management practices among the farmers and enforcing the effective banning of the most toxic pesticides will considerably reduce the number of acute pesticide poisoning episodes.

Pesticide Use and Self-Reported Symptoms of Acute Pesticide Poisoning among Aquatic Farmers in Phnom Penh, Cambodia

PubMed Central

Jensen, Hanne Klith; Konradsen, Flemming; Jørs, Erik; Petersen, Jørgen Holm; Dalsgaard, Anders

2011-01-01

Organophosphates and carbamates (OPs/CMs) are known for their acetylcholinesterase inhibiting character. A cross-sectional study of pesticide handling practices and self-perceived symptoms of acute pesticide poisoning was conducted using questionnaire-based interviews with 89 pesticide sprayers in Boeung Cheung Ek (BCE) Lake, Phnom Penh, Cambodia. The study showed that 50% of the pesticides used belonged to WHO class I + II and personal protection among the farmers were inadequate. A majority of the farmers (88%) had experienced symptoms of acute pesticide poisoning, and this was significantly associated with the number of hours spent spraying with OPs/CMs (OR = 1.14, CI 95%: 1.02–1.28). The higher educated farmers reduced their risk of poisoning by 55% for each extra personal protective measure they adapted (OR = 0.45, CI 95%: 0.22–0.91). These findings suggest that improving safe pesticide management practices among the farmers and enforcing the effective banning of the most toxic pesticides will considerably reduce the number of acute pesticide poisoning episodes. PMID:21234245

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

PubMed

Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

2017-02-01

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

The Installation Restoration Program Toxicology Guide. Volume 4

DTIC Science & Technology

1989-07-01

64.15 64-5 JP-4 Fuel-Water Partition Coefficients (K,) for Selected Hydrocarbons .......................... 64-20 04-6 Acute Toxicity of Components of JP...65.11 65-3 Equilibrium Partitioning of Select Gasoline Hydrocarbons in Model Environments ............... 65-14 65-4 Acute Toxicity of Components o...66-27 66-5 Acute Toxicity of Components of Fuel Oils ............ 66-37 67-1 Composition Dat,- for Stoddard Solvent

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

EPA Science Inventory

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

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Development of an acute toxicity test with the tropical marine amphipod Parhyale hawaiensis.

PubMed

Artal, Mariana Coletty; Dos Santos, Amanda; Henry, Theodore Burdick; Umbuzeiro, Gisela de Aragão

2018-03-01

There is a lack of suitable tropical marine species for ecotoxicity tests. An attractive model organism for ecotoxicology is the marine amphipod Parhyale hawaiensis, which is already a model for genetic and developmental studies. This species is widespread, can tolerate changes in salinity, is easy to handle and is representative of circumtropical regions. The aim of this work was to describe standardized procedures for laboratory husbandry, define conditions for acute toxicity tests, and to provide acute toxicity test results for some reference toxicants. Culturing conditions for the organism in the laboratory were established in reconstituted seawater (30 ± 2 salinity), 24 ± 2 °C, photoperiod 12/12 h light/dark. Acute toxicity test procedures were developed for 96 h-exposure time, and organisms at ages <7 days. The miniaturized version of the test, based on 96-well microplates and 200 µL of exposure media provided consistent results compared to larger exposure volumes (80-mL vials protocol). Acute toxicity of Ag, Cd, Cu, Zn and ammonia determined for P. hawaiensis were consistent to previous results for other marine amphipods. We conclude that P. hawaiensis can be successfully cultured in standardized conditions and be effectively used in acute toxicity testing. Further development and use of this model will enable standardized and reproducible ecotoxicology investigations in understudied and vulnerable tropical marine ecosystems.

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract

PubMed Central

Deshpande, Pallavi O.; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

Objective: To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek (Trigonella foenum-graecum L) seed extract in laboratory rats. Materials and Methods: The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. Results: The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. Conclusions: IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. SUMMARY Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control PMID:28539737

Study on acute toxicity of amoxicillin wastewater to Zebrafish

NASA Astrophysics Data System (ADS)

Xie, Weifang; Shen, Hongyan

2017-12-01

The main research in this paper is to obtain the effect of pharmaceutical wastewater on the acute toxicity of Zebrafish. The experimental method of exposure is used in this research. Experiments were carried out with different groups of pharmaceutical wastewater. Zebrafish was cultivated in a five liter fish tank. In the experiment, according to mortality, initially a 96h preliminary test was carried out at exposure concentrations to determine if the amoxicillin wastewater was toxic and to define the concentration range (24h LC100, 96h LC0) to be employed in the definitive tests. Based on the half lethal concentration of Zebrafish, the acute toxicity of amoxicillin wastewater to Zebrafish was calculated and the toxicity grade of wastewater was determined. In the experiment, the Zebrafish was exposed with amoxicillin wastewater during 96h. The 24h, 48h, 72h and 96h LC50 of amoxicillin wastewater on the Zebrafish were 63.10%, 53.70%, 41.69% and 40.74%, respectively. At 96h, the test time is the longest, and the value of LC50 is the smallest. In the observation period of 96 hours, the LC50 of amoxicillin wastewater were in the range of 40% ~ 60% and the value of Tua is 1 ~ 2. It indicates amoxicillin wastewater is low toxic wastewater when the experimental time is shorter than 48h, amoxicillin wastewater is moderate toxicity wastewater when the experimental time is higher than 48h. According to the experimental data, with the exposure time and the volume percentage of amoxicillin wastewater increases, the mortality rate of Zebrafish is gradually increased and the toxicity of amoxicillin wastewater increases. It indicates that the toxicity of amoxicillin wastewater is the biggest and the effect of wastewater on Zebrafish is greatest. In some ways, the toxicity of amoxicillin wastewater can be affected by the test time.

Outcomes and toxicities of stereotactic body radiation therapy for non-spine bone oligometastases

PubMed Central

Owen, Dawn; Laack, Nadia N.; Mayo, Charles S.; Garces, Yolanda I.; Park, Sean S.; Bauer, Heather J.; Nelson, Kathryn; Miller, Robert W.; Brown, Paul D.; Olivier, Kenneth R.

2015-01-01

Purpose Stereotactic body radiation therapy (SBRT) is being applied more widely for oligometastatic disease. This technique is now being used for non-spine bony metastases in addition to liver, spine, and lung. However, there are few studies examining the toxicity and outcomes of SBRT for non-spine bone metastases. Methods and Materials Between 2008 and 2012, 74 subjects with oligometastatic non-spine bony metastases of varying histologies were treated at the Mayo Clinic with SBRT. A total of 85 non-spine bony sites were treated. Median local control, overall survival, and progression-free survival were described. Acute toxicity (defined as toxicity <90 days) and late toxicity (defined as toxicity ≥90 days) were reported and graded as per standardized Common Toxicity Criteria for Adverse Events 4.0 criteria. Results The median age of patients treated was 60 years. The most common histology was prostate cancer (31%) and most patients had fewer than 3 sites of disease at the time of simulation (64%). Most of the non-spine bony sites lay within the pelvis (65%). Dose and fractionation varied but the most common prescription was 24 Gy/1 fraction. Local recurrence occurred in 7 patients with a median time to failure of 2.8 months. Local control was 91.8% at 1 year. With a median follow-up of 7.6 months, median SBRT specific overall survival and progression-free survival were 9.3 months and 9.7 months, respectively. Eighteen patients developed acute toxicity (mostly grade 1 and 2 fatigue and acute pain flare); 9 patients developed grade 1–2 late toxicities. Two patients developed pathologic fractures but both were asymptomatic. There were no late grade 3 or 4 toxicities. Conclusions Stereotactic body radiation therapy is a feasible and tolerable treatment for non-spine bony metastases. Longer follow-up will be needed to accurately determine late effects. PMID:24890360

Survival, mobility, and membrane-bound enzyme activities of freshwater planarian, Dugesia japonica, exposed to synthetic and natural surfactants.

PubMed

Li, Mei-Hui

2012-04-01

Surfactants are a major class of emerging pollutants widely used in large quantities in everyday life and commonly found in surface waters worldwide. Freshwater planarian was selected to examine the effects of different surfactants by measuring mortality, mobility, and membrane-bound enzyme activities. Among the 10 surfactants tested, the acute toxicities of betaine and polyethylene glycol (PEG-200) to planarians were relatively low, with a median lethal concentration (LC50) greater than 10,000 mg/L. The toxicity to planarians of the other eight surfactants based on 48-h LC50 could be arranged in the descending order of cetylpyridinum chloride (CPC) > 4-tert-octylphenol (4-tert-OP) > ammonium lauryl sulfate > benzalkonium chloride > saponin > sodium lauroylsarcosinate > dioctyl sulfosuccinate > dodecyl trimethyl ammonium bromide (DTAB). Both CPC and 4-tert-OP were very toxic to planarians, with 48-h LC50 values <1 mg/L. The median effective concentrations (EC50s) of planarian mobility were in the 0.1 to 50 mg/L range and were in the same range as the 24-h LC50 of planarians exposed to different surfactants, except for DTAB. In addition, significant inhibition of cholinesterase activity activities was found in planarians exposed to 4-tert-OP at 2.5 and 5 mg/L and to saponin at 10 mg/L after 2-h treatments. This result suggests that planarian mobility responses can be used as an alternative indicator for acute toxicity of surfactants after a very short exposure period. Copyright © 2012 SETAC.

Intra- and interlaboratory variability in acute toxicity tests with glochidia and juveniles of freshwater mussels (Unionidae)

USGS Publications Warehouse

Wang, N.; Augspurger, T.; Barnhart, M.C.; Bidwell, Joseph R.; Cope, W.G.; Dwyer, F.J.; Geis, S.; Greer, I.E.; Ingersoll, C.G.; Kane, C.M.; May, T.W.; Neves, R.J.; Newton, T.J.; Roberts, A.D.; Whites, D.W.

2007-01-01

The present study evaluated the performance and variability in acute toxicity tests with glochidia and newly transformed juvenile mussels using the standard methods outlined in American Society for Testing and Materials (ASTM). Multiple 48-h toxicity tests with glochidia and 96-h tests with juvenile mussels were conducted within a single laboratory and among five laboratories. All tests met the test acceptability requirements (e.g., ???90% control survival). Intralaboratory tests were conducted over two consecutive mussel-spawning seasons with mucket (Actinonaias ligamentina) or fatmucket (Lampsilis siliquoidea) using copper, ammonia, or chlorine as a toxicant. For the glochidia of both species, the variability of intralaboratory median effective concentrations (EC50s) for the three toxicants, expressed as the coefficient of variation (CV), ranged from 14 to 27% in 24-h exposures and from 13 to 36% in 48-h exposures. The intralaboratory CV of copper EC50s for juvenile fatmucket was 24% in 48-h exposures and 13% in 96-h exposures. Interlaboratory tests were conducted with fatmucket glochidia and juveniles by five laboratories using copper as a toxicant. The interlaboratory CV of copper EC50s for glochidia was 13% in 24-h exposures and 24% in 48-h exposures, and the interlaboratory CV for juveniles was 22% in 48-h exposures and 42% in 96-h exposures. The high completion success and the overall low variability in test results indicate that the test methods have acceptable precision and can be performed routinely. ?? 2007 SETAC.

Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

PubMed

Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

2011-04-01

Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA. Copyright © 2011 SETAC.

Identifying and designing chemicals with minimal acute aquatic toxicity

PubMed Central

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

2015-01-01

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

Identifying and designing chemicals with minimal acute aquatic toxicity.

PubMed

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

2015-05-19

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

Transformation of Physical DVHs to Radiobiologically Equivalent Ones in Hypofractionated Radiotherapy Analyzing Dosimetric and Clinical Parameters: A Practical Approach for Routine Clinical Practice in Radiation Oncology

PubMed Central

Thrapsanioti, Zoi; Karanasiou, Irene; Platoni, Kalliopi; Efstathopoulos, Efstathios P.; Matsopoulos, George; Dilvoi, Maria; Patatoukas, George; Chaldeopoulos, Demetrios; Kelekis, Nikolaos; Kouloulias, Vassilis

2013-01-01

Purpose. The purpose of this study was to transform DVHs from physical to radiobiological ones as well as to evaluate their reliability by correlations of dosimetric and clinical parameters for 50 patients with prostate cancer and 50 patients with breast cancer, who were submitted to Hypofractionated Radiotherapy. Methods and Materials. To achieve this transformation, we used both the linear-quadratic model (LQ model) and the Niemierko model. The outcome of radiobiological DVHs was correlated with acute toxicity score according to EORTC/RTOG criteria. Results. Concerning the prostate radiotherapy, there was a significant correlation between RTOG acute rectal toxicity and D 50 (P < 0.001) and V 60 (P = 0.001) dosimetric parameters, calculated for α/β = 10 Gy. Moreover, concerning the breast radiotherapy there was a significant correlation between RTOG skin toxicity and V ≥60 dosimetric parameter, calculated for both α/β = 2.3 Gy (P < 0.001) and α/β = 10 Gy (P < 0.001). The new tool seems reliable and user-friendly. Conclusions. Our proposed model seems user-friendly. Its reliability in terms of agreement with the presented acute radiation induced toxicity was satisfactory. However, more patients are needed to extract safe conclusions. PMID:24348743

In Vivo and In Vitro Toxicity Evaluation of Hydroethanolic Extract of Kalanchoe brasiliensis (Crassulaceae) Leaves

PubMed Central

Lima, Adley Antoninni Neves; Soares, Luiz Alberto Lira

2018-01-01

The species Kalanchoe brasiliensis, known as “Saião,” has anti-inflammatory, antimicrobial, and antihistamine activities. It also has the quercetin and kaempferol flavonoids, which exert their therapeutic activities. With extensive popular use besides the defined therapeutical properties, the study of possible side effects is indispensable. The objective of this study is to evaluate the toxicity in vitro and in vivo from the hydroethanolic extract of the leaves of K. brasiliensis. The action of the extract (concentrations from 0.1 to 1000 uL/100 uL) in normal and tumor cells was evaluated using the MTT method. Acute toxicity and subchronic toxicity were evaluated in mice with doses of 250 to 1000 mg/kg orally, following recognized protocols. The in vitro results indicated cytotoxic activity for 3T3 cell line (normal) and 786-0 (kidney carcinoma), showing the activity to be concentration-dependent, reaching 92.23% cell inhibition. In vivo, the extract showed no significant toxicity; only liver changes related to acute toxicity and some signs of liver damage, combining biochemical and histological data. In general, the extract showed low or no toxicity, introducing itself as safe for use with promising therapeutic potential. PMID:29593788

Aquatic toxicity of nine aircraft deicer and anti-icer formulations and relative toxicity of additive package ingredients alkylphenol ethoxylates and 4,5-methyl-1H-henzotriazoles.

PubMed

Corsi, Steven R; Geis, Steven W; Loyo-Rosales, Jorge E; Rice, Clifford P

2006-12-01

Characterization of the effects of aircraft deicer and anti-icer fluid (ADAF) runoff on aquatic organisms in receiving streams is a complex issue because the identities of numerous toxic additives are proprietary and not publicly available. Most potentially toxic and endocrine disrupting effects caused by ADAF are due to the numerous additive package ingredients which vary among manufacturers and types of ADAF formulation. Toxicity investigations of nine ADAF formulations indicate that endpoint concentrations for formulations of different manufacturers are widely variable. Type IV ADAF (anti-icers) are more toxic than Type I (deicers) for the four organisms tested (Vibrio fischeri, Pimephales promelas, Ceriodaphnia dubia, and Selenastrum capricornutum). Acute toxicity endpoint concentrations ranged from 347 to 7700 mg/L as ADAF for Type IV and from 1550 to 45,100 mg/L for Type I formulations. Chronic endpoint concentrations ranged from 70 to 1300 mg/L for Type IV and from 37 to 18,400 mg/L for Type I formulations. Alkylphenol ethoxylates and tolyltriazoles are two known classes of additives. Nonylphenol, nonylphenol ethoxylates, octylphenol, octylphenol ethoxylates, and 4,5-methyl-1H-benzotriazoles were quantified in the nine ADAF formulations, and toxicity tests were conducted with nonylphenol ethoxylates and 4,5-methyl-1H-benzotriazoles. Toxicity units computed for glycol and these additives, with respect to toxicity of the ADAF formulations, indicate that a portion of ADAF toxicity can be explained by the known additives and glycols, but much of the toxicity is due to unidentified additives.

Antioxidant, antimicrobial and toxicological properties of Schinus molle L. essential oils.

PubMed

Martins, Maria do Rosário; Arantes, Silvia; Candeias, Fátima; Tinoco, Maria Teresa; Cruz-Morais, Júlio

2014-01-01

Schinus molle L. has been used in folk medicine as antibacterial, antiviral, topical antiseptic, antifungal, antioxidant, anti-inflammatory, anti-tumoural as well as antispasmodic and analgesic; however, there are few studies of pharmacological and toxicological properties of Schinus molle essential oils. The aim of this study was to evaluate the antioxidant and antimicrobial activities of Schinus molle leaf and fruit essential oils, correlated with their chemical composition and evaluate their acute toxicity. The chemical composition of Schinus molle leaf and fruit essential oils were evaluated by GC-FID and GC-MS. Antioxidant properties were determined using the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical and β-carotene/linoleic acid methods. Antimicrobial properties were evaluated by the agar disc diffusion method and minimal inhibitory concentration assay. Toxicity in Artemia salina and acute toxicity with behavioural screening in mice were evaluated. The dominant compounds found in leaf and fruit essential oils (EOs) were monoterpene hydrocarbons, namely α-phellandrene, β-phellandrene, β-myrcene, limonene and α-pinene. EOs showed low scavenging antioxidant activity by the DPPH free radical method and a higher activity by the β-carotene/linoleic acid method. Antimicrobial activity of EOs was observed for Gram+, Gram- pathogenic bacteria and food spoilage fungi. EOs showed totoxicity for Artemia salina and lower toxicity in Swiss mice. The result showed that EOs of leaves and fruits of Schinus molle demonstrated antioxidant and antimicrobial properties, suggesting their potential use in food or pharmaceutical industries. © 2013 Published by Elsevier Ireland Ltd.

In vitro antibacterial activity and acute toxicity studies of aqueous-methanol extract of Sida rhombifolia Linn. (Malvaceae).

PubMed

Assam, Assam J P; Dzoyem, J P; Pieme, C A; Penlap, V B

2010-07-27

Many bacteria among the Enterobacteria family are involved in infectious diseases and diarrhoea. Most of these bacteria become resistant to the most commonly used synthetic drugs in Cameroon. Natural substances seem to be an alternative to this problem. Thus the aim of this research was to investigate the in vitro antibacterial activity of the methanol and aqueous-methanol extracts of Sida rhombifolia Linn (Malvaceae) against seven pathogenic bacteria involved in diarrhoea. Acute toxicity of the most active extract was determined and major bioactive components were screened. The agar disc diffusion and the agar dilution method were used for the determination of inhibition diameters and the Minimum Inhibitory Concentration (MICs) respectively. The acute toxicity study was performed according WHO protocol. The aqueous-methanol extract (1v:4v) was the most active with diameters of inhibition zones ranging from 8.7 - 23.6 mm, however at 200 microg/dic this activity was relatively weak compared to gentamycin. The MICs of the aqueous-methanol extract (1v:4v) varied from 49.40 to 78.30 microg/ml. Salmonella dysenteriae was the most sensitive (49.40 microg/ml). For the acute toxicity study, no deaths of rats were recorded. However, significant increase of some biochemical parameters such as aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatinine (CRT) were found. The phytochemical analysis of the aqueous methanol extract indicated the presence of tannins, polyphenols, alkaloids, glycosides, flavonoids and saponins The results showed that the aqueous-methanol extract of S. rhombifolia exhibited moderate antibacterial activity. Some toxic effects were found when rats received more than 8 g/kg bw of extract.

Predictors of Cosmetic Outcome Following MammoSite Breast Brachytherapy: A Single-Institution Experience of 100 Patients With Two Years of Follow-Up

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

Dragun, Anthony E.; Harper, Jennifer L.; Jenrette, Joseph M.

2007-06-01

Purpose: To identify the factors that predict for excellent cosmesis in patients who receive MammoSite breast brachytherapy (MBT). Methods and Materials: One hundred patients with Stage 0, I, or II adenocarcinoma of the breast underwent adjuvant therapy using MBT. A dose of 34 Gy, delivered in 10 fractions twice daily, was prescribed to 1-cm depth using {sup 192}Ir high-dose-rate brachytherapy. Patients were assessed for acute toxicity on the day of therapy completion, 4 weeks after therapy, and at least every 3 months by radiation, surgical, and/or medical oncologists. All available data were reviewed for documentation of cosmesis and rated usingmore » the Harvard Scale. All patients had a minimum follow-up of 6 months (median = 24 months). Results: Of 100 patients treated, 90 had adequate data and follow-up. Cosmesis was excellent in 62 (68.9%), good in 19 (21.1%), fair in 8 (8.9%), and poor in 1 (1.1%) patient. Using stepwise logistic regression, the factors that predicted for excellent cosmesis were as follows: the absence vs. presence of infection (p = 0.017), and the absence vs. presence of acute skin toxicity (p = 0.026). There was a statistically significant association between acute skin toxicity (present vs. absent) and balloon-to-skin distance (<8 vs. >8 mm, p = 0.001). Factors that did not predict for cosmesis were age, balloon placement technique, balloon volume, catheter days in situ, subcutaneous toxicity, and chemotherapy or hormonal therapy. Conclusions: The acute and late-term toxicity profiles of MBT have been acceptable. Cosmetic outcome is improved by proper patient selection and infection prevention.« less

Is it photosensitization or photodegradation when UV-B irradiation is combined with BDE-47? Evidence from the growth and reproduction changes of rotifer Brachionus plicatilis.

PubMed

Liu, Chunchen; Tang, Xuexi; Zhou, Bin; Jiang, Yongshun; Lv, Mengchen; Zang, Yu; Wang, You

2018-07-01

Ecotoxicological methods were applied in the present study, and the marine rotifer Brachionus plicatilis was used as the toxic endpoint to depict what occurred when 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) was combined with solar ultraviolet-B radiation (UV-B). B. plicatilis was exposed to three different combination methods of BDE-47 and UV-B at an equal toxicity ratio, including normal rotifer co-cultured with UV-B-irradiated BDE-47 (known as Method I), UV-B-irradiated rotifer co-cultured with BDE-47 exposure (known as Method II) and normal rotifer co-cultured with the simultaneous addition of BDE-47 and UV-B irradiation (known as Method III). Acute and chronic experiments were preformed to determine the toxicity differentiation according to the growth and reproduction changes in the rotifer. Twenty-four-hour acute experiments showed that the modes of three combined methods changed from antagonism to additive, to synergistic with the concentration/dose increment, and the contribution rates of Method I and Method II to Method III were calculated by approximately 40.4% and 59.6%, respectively. Chronic exposure to either the single stressor or the combination of stressors inhibited the growth and reproduction of the rotifer, demonstrating the inhibition of the population growth rate and the decrease in the larvae production. Three combined groups presented more serious damages compared to groups with single stress exposure, and the ascending sequence of toxicity was Method I

Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

PubMed

Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

2017-06-01

Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing

PubMed Central

Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J.; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

2017-01-01

Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. PMID:28069485

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

PubMed

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

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

A Prospective Study of Proton Beam Reirradiation for Esophageal Cancer

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

Fernandes, Annemarie, E-mail: Annemarie.fernandes@gmail.com; Berman, Abigail T.; Mick, Rosemarie

Purpose: Reirradiation to the esophagus carries a significant risk of complications. Proton therapy may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of previously radiated normal tissues. Methods and Materials: Between June 2010 and February 2014, 14 patients with a history of thoracic radiation and newly diagnosed or locally recurrent esophageal cancer began proton beam reirradiation on a prospective trial. Primary endpoints were feasibility and acute toxicity. Toxicity was graded according Common Toxicity Criteria version 4.0. Results: The median follow-up was 10 months (2-25 months) from the start of reirradiation. Eleven patients receivedmore » concurrent chemotherapy. The median interval between radiation courses was 32 months (10-307 months). The median reirradiation prescription dose was 54.0 Gy (relative biological effectiveness [RBE]) (50.4-61.2 Gy[RBE]), and the median cumulative prescription dose was 109.8 Gy (76-129.4 Gy). Of the 10 patients who presented with symptomatic disease, 4 patients had complete resolution of symptoms, and 4 had diminished or stable symptoms. Two patients had progressive symptoms. The median time to symptom recurrence was 10 months. Maximum acute nonhematologic toxicity attributable to radiation was grade 2 (64%, N=9), 3 (29%, N=4), 4 (0%), and 5 (7%, N=1). The acute grade 5 toxicity was an esophagopleural fistula more likely related to tumor progression than radiation. Grade 3 nonhematologic acute toxicities included dysphagia, dehydration, and pneumonia. There was 1 late grade 5 esophageal ulcer more likely related to tumor progression than radiation. There were 4 late grade 3 toxicities: heart failure, esophageal stenosis requiring dilation, esophageal ulceration from tumor, and percutaneous endoscopic gastrostomy tube dependence. The median time to local failure was 10 months, and the median overall survival was 14 months. Conclusions: Our data demonstrate that proton reirradiation is feasible, with an encouraging symptom control rate, modest radiation-related toxicity, and favorable survival in this high-risk population.« less

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

PubMed Central

2011-01-01

Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity categories of chemicals. Moreover, HCO-SLN significantly decreased the toxicity of tilmicosin. Normal clinic dosage of Til-HCO-SLN is safe as evaluated by acute toxicity. PMID:22098626

Postoperative Radiation Therapy for Prostate Cancer: Comparison of Conventional Versus Hypofractionated Radiation Regimens.

PubMed

Tandberg, Daniel J; Oyekunle, Taofik; Lee, W Robert; Wu, Yuan; Salama, Joseph K; Koontz, Bridget F

2018-06-01

To compare acute/late toxicity and biochemical control in contemporaneous prostate cancer patient cohorts treated with hypofractionated postprostatectomy radiation therapy (hypoPORT) or conventional PORT (coPORT). Consecutive patients treated with intensity modulated hypoPORT (2.5 Gy per fraction, median cumulative dose 65 Gy [range, 57.5-70 Gy]) or coPORT (1.8-2.0 Gy per fraction, median cumulative dose 66 Gy [range, 60-74 Gy]) between 2005 and 2016 at 2 institutions constituted the study cohort. Acute toxicity and cumulative late grade 2 and ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity incidences were calculated for all patients using the Kaplan-Meier method and compared between cohorts. Biochemical progression-free survival (bPFS) was calculated in patients with ≥12 months' follow-up. Median follow-up for all 461 patients was 38.6 months. Of the 461 patients, 167 (36%) received hypoPORT, and 294 (64%) patients received coPORT. The hypoPORT cohort had significantly worse baseline urinary incontinence. Acute grade ≥2 GU toxicity was more common after hypoPORT (22% vs 8%) (P = .0001). Late grade ≥3 GU toxicity cumulative incidence at 6 years was 11% (hypoPORT) and 4% (coPORT) (P = .0081). However, hypoPORT was not associated with late grade ≥2 GU toxicity on multivariate analysis (hazard ratio 1.39, 95% confidence interval 0.86-2.34) (P = .18). There was no difference in acute or late GI toxicity. In the subset of patients with ≥12 month's follow-up (n = 364, median follow-up 52 months), 4-year bPFS was 78% (95% CI 69.4-85.0) after hypoPORT (P = .0038) and 65% (95% CI 57.6-71.1) after coPORT. HypoPORT was not significant for bPFS on multivariate analysis (hazard ratio 0.64, 95% CI 0.41-1.02, P = .059). HypoPORT shows promising early biochemical control. After controlling for baseline urinary function, hypoPORT was not associated with greater GU toxicity than coPORT. © 2018 Elsevier Inc. Copyright © 2018 Elsevier Inc. All rights reserved.

Field Validation of Toxicity Tests to Evaluate the Potential for Beneficial Use of Produced Water

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

Joseph Bidwell; Jonathan Fisher; Naomi Cooper

2008-03-31

This study investigated potential biological effects of produced water contamination derived from occasional surface overflow and possible subsurface intrusion at an oil production site along the shore of Skiatook Lake, Oklahoma. We monitored basic chemistry and acute toxicity to a suite of standard aquatic test species (fathead minnow-Pimephales promelas, Daphnia pulex, Daphnia magna, and Ceriodaphnia dubia) in produced water and in samples taken from shallow groundwater wells on the site. Toxicity identification evaluations and ion toxicity modeling were used to identify toxic constituents in the samples. Lake sediment at the oil production site and at a reference site were alsomore » analyzed for brine intrusion chemically and by testing sediment toxicity using the benthic invertebrates, Chironomus dilutus, and Hyallela azteca. Sediment quality was also assessed with in situ survival and growth studies with H. azteca and the Asian clam, Corbicula fluminea, and by benthic macroinvertebrate community sampling. The produced water was acutely toxic to the aquatic test organisms at concentrations ranging from 1% to 10% of the whole produced water sample. Toxicity identification evaluation and ion toxicity modeling indicated major ion salts and hydrocarbons were the primary mixture toxicants. The standardized test species used in the laboratory bioassays exhibited differences in sensitivity to these two general classes of contaminants, which underscores the importance of using multiple species when evaluating produced water toxicity. Toxicity of groundwater was greater in samples from wells near a produced water injection well and an evaporation pond. Principle component analyses (PCA) of chemical data derived from the groundwater wells indicated dilution by lake water and possible biogeochemical reactions as factors that ameliorated groundwater toxicity. Elevated concentrations of major ions were found in pore water from lake sediments, but toxicity from these ions was limited to sediment depths of 10 cm or greater, which is outside of the primary zone of biological activity. Further, exposure to site sediments did not have any effects on test organisms, and macroinvertebrate communities did not indicate impairment at the oil production site as compared to a reference site. In situ experiments with H. azteca and C. fluminea, indicated a sublethal site effect (on growth of both species), but these could not be definitively linked with produced water infiltration. Severe weather conditions (drought followed by flooding) negatively influenced the intensity of lake sampling aimed at delineating produced water infiltration. Due to the lack of clear evidence of produced water infiltration into the sub-littoral zone of the lake, it was not possible to assess whether the laboratory bioassays of produced water effectively indicate risk in the receiving system. However, the acutely toxic nature of the produced water and general lack of biological effects in the lake at the oil production site suggest minimal to no produced water infiltration into surficial lake sediments and the near-shore water column. This study was able to demonstrate the utility of ion toxicity modeling to support data from toxicity identification evaluations aimed at identifying key toxic constituents in produced water. This information could be used to prioritize options for treating produced water in order to reduce toxic constituents and enhance options for reuse. The study also demonstrated how geographic information systems, toxicity modeling, and toxicity assessment could be used to facilitate future site assessments.« less

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

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

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

Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu; Ayala, Deandra; Jensen, Courtney

2012-02-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patientsmore » experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.« less

Profiling Animal Toxicants by Automatically Mining Public Bioassay Data: A Big Data Approach for Computational Toxicology

PubMed Central

Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

2014-01-01

In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities. PMID:24950175

Profiling animal toxicants by automatically mining public bioassay data: a big data approach for computational toxicology.

PubMed

Zhang, Jun; Hsieh, Jui-Hua; Zhu, Hao

2014-01-01

In vitro bioassays have been developed and are currently being evaluated as potential alternatives to traditional animal toxicity models. Already, the progress of high throughput screening techniques has resulted in an enormous amount of publicly available bioassay data having been generated for a large collection of compounds. When a compound is tested using a collection of various bioassays, all the testing results can be considered as providing a unique bio-profile for this compound, which records the responses induced when the compound interacts with different cellular systems or biological targets. Profiling compounds of environmental or pharmaceutical interest using useful toxicity bioassay data is a promising method to study complex animal toxicity. In this study, we developed an automatic virtual profiling tool to evaluate potential animal toxicants. First, we automatically acquired all PubChem bioassay data for a set of 4,841 compounds with publicly available rat acute toxicity results. Next, we developed a scoring system to evaluate the relevance between these extracted bioassays and animal acute toxicity. Finally, the top ranked bioassays were selected to profile the compounds of interest. The resulting response profiles proved to be useful to prioritize untested compounds for their animal toxicity potentials and form a potential in vitro toxicity testing panel. The protocol developed in this study could be combined with structure-activity approaches and used to explore additional publicly available bioassay datasets for modeling a broader range of animal toxicities.

A comparison of the efficacy of new asymmetric bispyridinium oximes (K027, K048) with currently available oximes against tabun by in vivo methods.

PubMed

Kassa, Jiri; Kuca, Kamil; Cabal, Jiri; Paar, Martin

2006-10-01

The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in reactivating tabun-inhibited acetylcholinesterase (AChE) and in eliminating tabun-induced acute toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined the percent of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime, the most efficacious known reactivators of tabun-inhibited AChE. These were also found to be sufficiently efficacious in the elimination of acute lethal toxic effects in tabun-poisoned rats. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and in counteracting acute lethal effects of tabun. In addition, our results confirm that the efficacy of oximes in reactivating tabun-inhibited AChE in blood, diaphragm, and brain correlates with the potency of oximes in protecting rats poisoned with supralethal doses of tabun.

[Comparative toxicity of triacetin and diethylene glycol diacetate].

PubMed

Nosko, M

1977-01-01

The approximative lethal dose of triacetin and diethylene glycole acetate is determined after the method of Deihmann and Leblanc. Experiments are conducted on white rats to establish the acute and subacute oral, dermal and inhalatory toxicity of the two substances. Changes in weight, liver and kidneys weight coefficient, hematopoiesis and hepatic function (biochemical and pathomorphological), as well as the stimulating effect on mucosa and skin are studied. The results of the study show a weak stimulating action on mucosa and skin, and insignificant cumulation. Emphasis is laid on the functional character of changes in the values of some enzymes -- alkaline phosphatase, cytochrome oxidase, cholinesterase -- and of the pathomorphologically established parenchymatous dystrophy. Presumably, it is a matter of changes more strongly manifested in imported triacetin. The conclusion is reached that imported triacetin may be substituted for lokally produced diethylene glycoldiacetate which proves to be with a lower acute and subacute toxicity.

Influence of salinity and temperature on acute toxicity of cadmium to Mysidopsis bahia molenock

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

Voyer, R.A.; Modica, G.

1990-01-01

Acute toxicity tests were conducted to compare estimates of toxicity, as modified by salinity and temperature, based on response surface techniques with those derived using conventional test methods, and to compare effect of a single episodic exposure to cadmium as a function of salinity with that of continuous exposure. Regression analysis indicated that mortality following continuous 96-hr exposure is related to linear and quadratic effects of salinity and cadmium at 20 C, and to the linear and quadratic effects of cadmium only at 25C. LC50s decreased with increases in temperature and decreases in salinity. Based on the regression model developed,more » 96-hr LC50s ranged from 15.5 to 28.0 micro Cd/L at 10 and 30% salinities, respectively, at 25C; and from 47 to 85 microgram Cd/L at these salinities at 20C.« less

Acute toxicity of ingested fluoride.

PubMed

Whitford, Gary Milton

2011-01-01

This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve. Copyright © 2011 S. Karger AG, Basel.

Toxicological studies of stem bark extract from Schefflera barteri Harms (Araliaceae).

PubMed

Atsafack, Serge Secco; Kuiate, Jules-Roger; Mouokeu, Raymond Simplice; Koanga Mogtomo, Martin Luther; Tchinda, Alembert Tiabou; De Dieu, Tamokou Jean; Magnifouet Nana, Huguette; Ebelle Etame, Rébecca Madeleine; Biyiti, Lucie; Ngono Ngane, Rosalie Annie

2015-03-07

The use of herbal medicines as complements or alternatives to orthodox medicines has been on the increase. There has been the erroneous belief that these medicines are free from adverse effects. Schefflera barteri is popularly used in the West region of Cameroon for the treatment of various diseases such as diarrhea, spasm, pneumonia and animals bite. Considering the ethnopharmacological relevance of this plant, this study was designed to investigate the possible toxic effects of the stem bark extract of S. barteri. The extract was prepared by maceration of stem bark dry powder in methylene chloride/methanol mixture. Phytochemical analysis was performed by chemical reaction method. Oral acute toxicity study was carried out by administering single geometric increasing doses (2 to 16 g/kg body weight) of plant extract to Swiss albino mice. For sub-acute toxicity study, repeated doses (100, 200, 400 and 800 mg/kg bw) of plant extract were given to Wistar albino rats for 28 consecutive days by oral route. At the end of the treatment period, hematological and biochemical parameters were assessed, as well as histopathological studies. Phytochemical analysis of stem bark extract of S. barteri revealed the presence of anthocyanins, anthraquinons and saponins. Acute toxicity results showed that the LD50 was greater than 16000 mg/kg. Sub-acute treatment significantly (P < 0.05) increased the level of serum transaminase, proteins and HDL cholesterol. On the other hand, the extract significantly (P < 0.05) reduced the level of leucocytes as well as neutrophils, basophils and monocytes in female. No significant variation of serum creatinine, LDL cholesterol, serum triglycerides as well as liver, spleen, testicles and ovaries proteins was noted. Histopathological analysis of organs showed vascular congestion, inflammation of peri-portal and vacuolization of hepatocytes at the level of the liver. Leucocytes infiltration of peri-portal veins were noticed on lungs and liver cells as well as inflammatory peri-bronchial and basal membranes seminar tube merely joined on lungs and testis respectively. The results suggest that acute administration of the stem bark extract of S. barteri is associated with signs of toxicity, administration over a long duration provokes hepatotoxicity, testes and lungs toxicities.

Combined endosulfan and cypermethrin-induced toxicity to embryo-larval development of Rhinella arenarum.

PubMed

Svartz, Gabriela V; Aronzon, Carolina M; Pérez Coll, Cristina S

2016-01-01

The combined effects of two widely used pesticides, endosulfan and cypermethrin, on survival of embryo-larval development of the South American toad (Rhinella arenarum) were examined. The toxicity bioassays were performed according to the AMPHITOX test. Embryos and larvae were exposed to mixtures of these pesticides at equitoxic ratios from acute or chronic exposure to evaluate interaction effects. The results were analyzed using both Marking's additive index and combination index (CI)-isobologram methods. Acute (96-h) and intermediate (168-h) toxicity of endosulfan-cypermethrin mixtures remained almost constant for larvae and embryos, but when exposure duration was increased, there was a significant elevation in toxicity, obtaining chronic (240-h) no-observed-effect concentrations (NOEC) values of 0.045 and 0.16 mg/L for embryos and larvae, respectively. These are environmentally relevant concentrations that reflect a realistic risk of this pesticide mixture to this native amphibian species. The toxicity increment with the exposure duration was coincident with the central nervous system development on embryos reaching the larval period, the main target organ of these pesticides. The interactions of the pesticide mixtures at acute and chronic exposure were antagonistic for embryo development (CI > 1), and additive (CI = 1) for larvae, while chronic exposure interactions were synergistic (CI < 1) for both developmental periods. Data indicated that endosulfan-cypermethrin mixtures resulted in different interaction types depending on duration and developmental stage exposed. As a general pattern and considering conditions of overall developmental period and chronic exposure, this pesticide mixture usually applied in Argentine crop fields is synergistic with respect to toxicity for this native amphibian species.

[The morphofunctional changes in the rat lung tissue during simulation of acute fatal poisoning with household gas].

PubMed

Kalinina, E Iu; Iagmurov, O D

2014-01-01

The methods of light microscopy, immunohistochemistry, and electron microscopy were employed to study the morphofunctional changes in epithelium of bronchial and respiratory segments of the rat lungs used as models of acute fatal poisoning with household gas. It was shown that this toxic effect induces the pathological process involving all the elements of the epithelial layer in the bronchial and respiratory segments of the lungs of experimental animals. At the ultrastructural level, mitochondria and endoplasmic reticulum structures are affected, with the death of epithelial cells leading to the damage of the aerohematic barrier. The toxic effect of the gaseous mixture on the membranes causes the destruction of various elements of the epithelial layer. The results of this study help to understand the mechanisms of death in the case of acute fatal poisoning with household gas.

Radiochemotherapy in Anal Cancer: cCR, clinical outcomes and quality of life using two different treatment schedules

PubMed Central

Di Santo, Sara; Trignani, Marianna; Neri, Matteo; Milano, Angelo; Innocenti, Paolo; Taraborrelli, Maria; Augurio, Antonietta; Vinciguerra, Annamaria; Di Tommaso, Monica; Ursini, Lucia Anna; Di Pilla, Angelo; Di Nicola, Marta; Genovesi, Domenico

2014-01-01

Aim Main endpoint was a response rate to therapy; secondary endpoints were disease-free survival, overall survival, acute and late toxicities, specially in terms of anorectal and urinary continence. Background Radiochemotherapy for anal cancer achieves a good clinical response, locoregional control, anal function preservation. However, oncologic outcomes can differ using radiotherapy plus fluorouracil and mytomicin vs. cisplatin and fluorouracil. Methods Between 2000 and 2012, 27 anal cancer patients receiving radiotherapy combined with two different radiochemotherapy schedules, fluorouracil and mytomicin (group A) and cisplatin plus fluorouracil (group B). The Kaplan–Meier method was also used to estimate local control, overall survival and disease free survival. Statistical significance between curves was evaluated using the Log-rank test. Results Complete pathological response was found in 85.2% of patients, with higher rates of response in the group A (100% vs. 63.6%, p = 0.039). No significantly difference was found between the two groups for the other endpoints. Low rates of both acute and late toxicities were recorded. Conclusion Radiotherapy plus fluorouracil and mytomicin provide a better complete pathological response than radiotherapy plus cisplatin and fluorouracil and a greater rate of anal sphincter function preservation. Globally, radiochemotherapy of the anal cancer provides excellent clinical outcomes with a good profile of acute and late toxicity, without difference between the two groups studied. PMID:25859401

Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

2010-01-01

The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

Worsening renal function definition is insufficient for evaluating acute renal failure in acute heart failure

PubMed Central

Hata, Noritake; Kobayashi, Nobuaki; Okazaki, Hirotake; Matsushita, Masato; Shibata, Yusaku; Nishigoori, Suguru; Uchiyama, Saori; Asai, Kuniya; Shimizu, Wataru

2018-01-01

Abstract Aims Whether or not the definition of a worsening renal function (WRF) is adequate for the evaluation of acute renal failure in patients with acute heart failure is unclear. Methods and results One thousand and eighty‐three patients with acute heart failure were analysed. A WRF, indicated by a change in serum creatinine ≥0.3 mg/mL during the first 5 days, occurred in 360 patients while no‐WRF, indicated by a change <0.3 mg/dL, in 723 patients. Acute kidney injury (AKI) upon admission was defined based on the ratio of the serum creatinine value recorded on admission to the baseline creatinine value and placed into groups based on the degree of AKI: no‐AKI (n = 751), Class R (risk; n = 193), Class I (injury; n = 41), or Class F (failure; n = 98). The patients were assigned to another set of four groups: no‐WRF/no‐AKI (n = 512), no‐WRF/AKI (n = 211), WRF/no‐AKI (n = 239), and WRF/AKI (n = 121). A multivariate logistic regression model found that no‐WRF/AKI and WRF/AKI were independently associated with 365 day mortality (hazard ratio: 1.916; 95% confidence interval: 1.234–2.974 and hazard ratio: 3.622; 95% confidence interval: 2.332–5.624). Kaplan–Meier survival curves showed that the rate of any‐cause death during 1 year was significantly poorer in the no‐WRF/AKI and WRF/AKI groups than in the WRF/no‐AKI and no‐WRF/no‐AKI groups and in Class I and Class F than in Class R and the no‐AKI group. Conclusions The presence of AKI on admission, especially Class I and Class F status, is associated with a poor prognosis despite the lack of a WRF within the first 5 days. The prognostic ability of AKI on admission may be superior to WRF within the first 5 days. PMID:29388735

Clinical Toxicities and Dosimetric Parameters After Whole-Pelvis Versus Prostate-Only Intensity-Modulated Radiation Therapy for Prostate Cancer

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

Deville, Curtiland, E-mail: deville@uphs.upenn.ed; Both, Stefan; Hwang, Wei-Ting

2010-11-01

Purpose: To assess whether whole-pelvis (WP) intensity-modulated radiation therapy (IMRT) is associated with increased toxicity compared with prostate-only (PO) IMRT. Methods and Materials: We retrospectively analyzed all patients with prostate cancer undergoing definitive IMRT to 79.2 Gy with concurrent androgen deprivation at our institution from November 2005 to May 2007 with a minimum follow-up of 12 months. Thirty patients received initial WP IMRT to 45 Gy in 1.8-Gy fractions, and thirty patients received PO IMRT. Study patients underwent computed tomography simulation and treatment planning by use of predefined dose constraints. Bladder and rectal dose-volume histograms, maximum genitourinary (GU) and gastrointestinalmore » (GI) Radiation Therapy Oncology Group toxicity grade, and late Grade 2 or greater toxicity-free survival curves were compared between the two groups by use of the Student t test, Fisher exact test, and Kaplan-Meier curve, respectively. Results: Bladder minimum dose, mean dose, median dose, volume receiving 5 Gy, volume receiving 20 Gy, volume receiving 40 Gy, and volume receiving 45 Gy and rectal minimum dose, median dose, and volume receiving 20 Gy were significantly increased in the WP group (all p values < 0.01). Maximum acute GI toxicity was limited to Grade 2 and was significantly increased in the WP group at 50% vs. 13% the PO group (p = 0.006). With a median follow-up of 24 months (range, 12-35 months), there was no difference in late GI toxicity (p = 0.884) or in acute or late GU toxicity. Conclusions: Despite dosimetric differences in the volume of bowel, bladder, and rectum irradiated in the low-dose and median-dose regions, WP IMRT results only in a clinically significant increase in acute GI toxicity, in comparison to PO IMRT, with no difference in GU or late GI toxicity.« less

TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

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

Liu, T; Yang, X; Curran, W

2014-06-15

Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) wasmore » 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest that ultrasound imaging may be used to improve early detection of normal-tissue toxicity in breast-cancer RT.« less

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

PubMed

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

2011-08-01

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

Comparing anti-hyperglycemic activity and acute oral toxicity of three different trivalent chromium complexes in mice.

PubMed

Li, Fang; Wu, Xiangyang; Zou, Yanmin; Zhao, Ting; Zhang, Min; Feng, Weiwei; Yang, Liuqing

2012-05-01

Three different ligands (rutin, folate and stachyose) of chromium(III) complexes were compared to examine whether they have similar effect on anti-hyperglycemic activity as well as the acute toxicity status. Anti-hyperglycemic activities of chromium rutin complex (CrRC), chromium folate complex (CrFC) and chromium stachyose complex (CrSC) were examined in alloxan-induced diabetic mice with daily oral gavage for a period of 2 weeks at the dose of 0.5-3.0 mg Cr/kg. Acute toxicities of CrRC and CrFC were tested using ICR mice at the dose of 1.0-5.0 g/kg with a single oral gavage and observed for a period of 2 weeks. Biological activities results indicated that only CrRC and CrFC could decrease blood glucose level, reduce the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and increase liver glycogen level. In acute toxicity study, LD(50) values for both CrRC and CrFC were above 5.0 g/kg. The minimum lethal dose for CrFC was above 5.0 g/kg, while that for CrRC was 1.0 g/kg. Anti-diabetic activity of those chromium complexes was not similar and their acute toxicities were also different. CrFC represent an optimal chromium supplement among those chromium complexes with potential therapeutic value to control blood glucose in diabetes and non-toxicity in acute toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

The acute toxicity of major ion salts to Ceriodaphnia dubia: III. Mathematical models for mixture toxicity

EPA Science Inventory

Based on previous research on the acute toxicity of major ions (Na+, K+, Ca2+, Mg2+, Cl, SO42, and HCO3/CO32) to C. dubia, two mathematical models were developed for predicting the LC50 for any ion mixture, excluding those dominated by K toxicity. One model addresses a mechanism...

The Preparation of Some Compounds for Testing as Insect Repellents

DTIC Science & Technology

1945-12-28

have been submitted for 90-day subacute toxicity studies « 0-7139, 0-7209 and 0-7227 have passed acute toxicity tests (0- 7227 with reservations...but have not been submitted for 90-day subacute toxicity studies , 0-7392, 0-7430 and 0-13058 have been submitted for acute toxicity tests. Forty-fivo...evaluate adequately the promising candidate insect repellents prepared under this contract. Some toxicity studies as indicated above are being made

Acute and subacute oral toxicity of periodate salts in rats.

PubMed

Lent, Emily May; Crouse, Lee C B; Eck, William S

2017-02-01

Periodate salts are being developed as potential replacements for perchlorate due to potential health hazards associated with exposure to perchlorate. The aim of this study was to investigate acute and subacute effects of periodate salts in rats. Acute oral toxicity of potassium and sodium periodate was determined using the Sequential Stage-Wise Probit method. The LD 50 for potassium periodate was 732 (95% CI = 539-838, slope = 13.4) and 685 mg/kg (95% CI = 580-809, slope = 10.6) for females and males, respectively. The LD 50 for sodium periodate was 318 (95% CI = 292-347, slope = 24.3) and 741 mg/kg (95% CI = 704-779, slope = 31.2) for females and males, respectively. In the subacute study, rats were administered sodium periodate at five doses (1/16 LD 50 up to LD 50 ) or distilled water for 14-days via oral gavage. Female rats in the 318 mg/kg-day group and male rats in the 185, 370, and 741 mg/kg-day groups exhibited moribundity, kidney toxicity, uremia, and a stress response. BMDL 10 s of 17.2 and 33.7 mg/kg-day were derived for females and males, respectively. Comparison with the NOAEL for perchlorate-induced thyroid toxicity in rats (0.009 mg/kg-day) suggests sodium periodate is less toxic than perchlorate on a subacute basis. Copyright © 2016. Published by Elsevier Inc.

First reported case in the UK of acute prolonged neuropsychiatric toxicity associated with analytically confirmed recreational use of phenazepam.

PubMed

Dargan, Paul I; Davies, Susannah; Puchnarewicz, Malgorzata; Johnston, Atholl; Wood, David M

2013-03-01

There is increasing evidence from around Europe of the availability and misuse of long-acting benzodiazepines such as phenazepam. There is little information on the acute toxicity of these compounds; we describe here a case of analytically confirmed phenazepam-related acute toxicity. A 42-year-old man with no previous medical or psychiatric history was brought to the Emergency Department by his friends because he had developed prolonged ongoing confusion and disorientation following use of up to three different "legal high" powders. There was no obvious medical cause for this acute confusion and disorientation. His symptoms continued for approximately 60 h after suspected use. Subsequent toxicological analysis of a serum sample confirmed use of phenazepam (concentration 0.49 mg/L); no other drugs were detected during an extensive analytical screening. This is the second case of analytically confirmed acute toxicity related to phenazepam in Europe. This adds to the scant published information on the acute toxicity of this drug, and will provide healthcare and legislative authorities with further information on which to base advice and consideration of the need for its control.

An interspecies correlation model to predict acute dermal toxicity of plant protection products to terrestrial life stages of amphibians using fish acute toxicity and bioconcentration data.

PubMed

Weltje, Lennart; Janz, Philipp; Sowig, Peter

2017-12-01

This paper presents a model to predict acute dermal toxicity of plant protection products (PPPs) to terrestrial amphibian life stages from (regulatory) fish data. By combining existing concepts, including interspecies correlation estimation (ICE), allometric relations, lethal body burden (LBB) and bioconcentration modelling, an equation was derived that predicts the amphibian median lethal dermal dose (LD 50 ) from standard acute toxicity values (96-h LC 50 ) for fish and bioconcentration factors (BCF) in fish. Where possible, fish BCF values were corrected to 5% lipid, and to parent compound. Then, BCF values were adjusted to an exposure duration of 96 h, in case steady state took longer to be achieved. The derived correlation equation is based on 32 LD 50 values from acute dermal toxicity experiments with 15 different species of anuran amphibians, comprising 15 different PPPs. The developed ICE model can be used in a screening approach to estimate the acute risk to amphibian terrestrial life stages from dermal exposures to PPPs with organic active substances. This has the potential to reduce unnecessary testing of vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute aquatic toxicity of biodiesel fuels

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

Wright, B.; Haws, R.; Little, D.

1995-12-31

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

[Acute toxicity analysis performance of CellSense biosensor with E. coli].

PubMed

Wang, Xue-Jiang; Wang, Hong; Zhao, Jian-Fu; Xia, Si-Qing; Zhao, Hong-Ning

2009-04-15

E. coli microbial electrodes for CellSense biosensor were prepared by polycarbonate membrane immobilization process, and their performance for heavy metals and toxic organic compounds acute toxicity determination were studied. The results showed that when E. coli was in logarithmic and stationary phase, the CellSense biosensor with E. coli showed good performance in heavy metal ions and organic pollutants acute toxicity analysis, when E. coli was in its decline phase, the stability and sensitivity of the CellSense biosensor was poor. The EC50 values of Hg2+, Cu2+, Zn2+, o-chlorophenol (2-CP) and p-nitrophenol (4-NP) detected by CellSense biosensor with E. coli were 0.6, 3.1, 5.8, 180 and 94 microg/mL, respectively. The immobilized E. coli electrodes could still suit for acute toxicity assessment after 2 months storage at 4 degrees C.

Dosimetric rationale and early experience at UFPTI of thoracic proton therapy and chemotherapy in limited-stage small cell lung cancer.

PubMed

Colaco, Rovel J; Huh, Soon; Nichols, Romaine C; Morris, Christopher G; D'Agostino, Harry; Flampouri, Stella; Li, Zuofeng; Pham, Dat C; Bajwa, Abubakr A; Hoppe, Bradford S

2013-04-01

Concurrent chemoradiotherapy (CRT) is the standard of care in patients with limited-stage small cell lung cancer (SCLC). Treatment with conventional x-ray therapy (XRT) is associated with high toxicity rates, particularly acute grade 3+ esophagitis and pneumonitis. We present outcomes for the first known series of limited-stage SCLC patients treated with proton therapy and a dosimetric comparison of lung and esophageal doses with intensity-modulated radiation therapy (IMRT). Six patients were treated: five concurrently and one sequentially. Five patients received 60-66 CGE in 30-34 fractions once daily and one patient received 45 CGE in 30 fractions twice daily. All six patients received prophylactic cranial irradiation. Common Terminology Criteria for Adverse Events, v3.0, was used to grade toxicity. IMRT plans were also generated and compared with proton plans. The median follow-up was 12.0 months. The one-year overall and progression-free survival rates were 83% and 66%, respectively. There were no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis, and no other acute grade 3+ non-hematological toxicities were seen. One patient with a history of pulmonary fibrosis and atrial fibrillation developed worsening symptoms four months after treatment requiring oxygen. Three patients died: two of progressive disease and one after a fall; the latter patient was disease-free at 36 months after treatment. Another patient recurred and is alive, while two patients remain disease-free at 12 months of follow-up. Proton therapy proved superior to IMRT across all esophageal and lung dose volume points. In this small series of SCLC patients treated with proton therapy with radical intent, treatment was well tolerated with no cases of acute grade 3+ esophagitis or acute grade 2+ pneumonitis. Dosimetric comparison showed better sparing of lung and esophagus with proton therapy. Proton therapy merits further investigation as a method of reducing the toxicity of CRT.

Synergistic toxicity and physiological impact of imidacloprid alone and binary mixtures with seven representative pesticides on honey bee (Apis mellifera)

USDA-ARS?s Scientific Manuscript database

Imidacloprid is the most widely used insecticide in the world. In this study, we used spraying methods to simulate field exposures of bees to formulated imidacloprid (Advise® 2FL) alone and binary mixtures with seven pesticides from different classes. Synergistic toxicity was detected from mixtures ...

Web-based Interspecies Correlation Estimation

EPA Science Inventory

Web-ICE estimates acute toxicity (LC50/LD50) of a chemical to a species, genus, or family from the known toxicity of the chemical to a surrogate species. Web-ICE has modules to predict acute toxicity to aquatic (fish and invertebrates) and wildlife (birds and mammals) taxa for us...

Acute toxicity and associated mechanisms of four strobilurins in algae.

PubMed

Liu, Xiaoxu; Wang, Yu; Chen, Hao; Zhang, Junli; Wang, Chengju; Li, Xuefeng; Pang, Sen

2018-06-01

Strobilurins have been reported highly toxic to non-target aquatic organisms but few illustrated how they cause toxic effects on algae. This study investigated the acute toxicity of Kresoxim-methy (KRE), Pyraclostrobin (PYR), Trifloxystrobin (TRI) and Picoxystrobin (PIC) on two algae and their toxicity mechanisms. Four strobilurins showed lower toxic effects on Chlorella pyrenoidsa but higher on Chlorella vulgaris. bc1 complex activities in C. vulgaris were significantly inhibited by all strobilurins, suggesting bc 1 complex might be the target of strobilurin toxicity in algae. Moreover, SOD, CAT and POD activities were significantly up-regulated by all doses of KRE, PYR and PIC. In contrast, low concentrations of TRI stimulated SOD and POD activities but highest concentration significantly inhibited those activities. Comet assays showed damaged DNA in C. vulgaris by four strobulirins, suggesting their potential genotoxic threats to algae. The results illustrated acute toxicity by strobulirins on algae and their possible toxicity mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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

Okunieff, Paul; Xu Jianhua; Hu Dongping

2006-07-01

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

Acute and sub-chronic toxicity studies of honokiol microemulsion.

PubMed

Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

2015-04-01

The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

The Acute and Chronic Toxicity of 3,5-Dinitroaniline, 1,3- Dinitrobenzene, and 1,3,5-Trinitrobenzene to Freshwater Aquatic Organisms

DTIC Science & Technology

1983-10-01

algicidal . TEST METHODOLOGIES Static Acute Tests For both fish and daphnid tests, static acute methods generally followed those recommended by the American...algae previously exposed to 85.6 mg/L showed renewed growth. The 85.6 mg/L exposure level is therefore considered to be algicidal , while...17.3 mg/L TNB were algicidal , while the lower concentrations (0.10 and 0.17 mg/L) were algistatic, in that renewed growth occurred after exposed cells

Acute photo-induced toxicity and toxicokinetics of single compounds and mixtures of polycyclic aromatic hydrocarbons in zebrafish.

PubMed

Willis, Alison M; Oris, James T

2014-09-01

The present study examined photo-induced toxicity and toxicokinetics for acute exposure to selected polycyclic aromatic hydrocarbons (PAHs) in zebrafish. Photo-enhanced toxicity from co-exposure to ultraviolet (UV) radiation and PAHs enhanced the toxicity and exhibited toxic effects at PAH concentrations orders of magnitude below effects observed in the absence of UV. Because environmental exposure to PAHs is usually in the form of complex mixtures, the present study examined the photo-induced toxicity of both single compounds and mixtures of PAHs. In a sensitive larval life stage of zebrafish, acute photo-induced median lethal concentrations (LC50s) were derived for 4 PAHs (anthracene, pyrene, carbazole, and phenanthrene) to examine the hypothesis that phototoxic (anthracene and pyrene) and nonphototoxic (carbazole and phenanthrene) pathways of mixtures could be predicted from single exposures. Anthracene and pyrene were phototoxic as predicted; however, carbazole exhibited moderate photo-induced toxicity and phenanthrene exhibited weak photo-induced toxicity. The toxicity of each chemical alone was used to compare the toxicity of mixtures in binary, tertiary, and quaternary combinations of these PAHs, and a predictive model for environmental mixtures was generated. The results indicated that the acute toxicity of PAH mixtures was additive in phototoxic scenarios, regardless of the magnitude of photo-enhancement. Based on PAH concentrations found in water and circumstances of high UV dose to aquatic systems, there exists potential risk of photo-induced toxicity to aquatic organisms. © 2014 SETAC.

11C choline PET guided salvage radiotherapy with volumetric modulation arc therapy and hypofractionation for recurrent prostate cancer after HIFU failure: preliminary results of tolerability and acute toxicity.

PubMed

Alongi, Filippo; Liardo, Rocco L E; Iftode, Cristina; Lopci, Egesta; Villa, Elisa; Comito, Tiziana; Tozzi, Angelo; Navarria, Pierina; Ascolese, Anna M; Mancosu, Pietro; Tomatis, Stefano; Bellorofonte, Carlo; Arturo, Chiti; Scorsetti, Marta

2014-10-01

The purpose of this work was to evaluate tolerance, feasibility and acute toxicity in patients undergoing salvage radiotherapy after high-intensity focused ultrasound (HIFU) failure. From 2005 to 2011 a total of 15 patients were treated with HIFU as primary radical treatment. Between July 2011 and February 2013, all 15 patients presented biochemical relapse after HIFU and 11C choline PET documenting intrapostatic-only failure. Salvage EBRT was performed with moderate hypofractionation schedule in 28 fractions with volumetric modulation arc therapy (VMAT). Genito-urinary (GU) and rectal and bowel toxicity were scored by common terminology criteria for adverse events version 4 (CTCAE V.4) scale. Biochemical response was assessed by ASTRO Phoenix criteria. Median age of patients was 67 years (range: 53-85). The median Gleason score was 7 (range: 6-9). The median prostate specific antigen (PSA) at the time of biochemical relapse after HIFU was 5.2 ng/mL (range: 2-64.2). Seven of the 15 patients received androgen deprivation therapy (ADT) started after HIFU failure, interrupted before 11C choline PET and radiotherapy. Median prescribed dose was 71.4 Gy (range: 71.4-74.2 Gy) in 28 fractions. No radiation related major upper gastrointestinal (GI), rectal and GU toxicity were experienced. GU, acute grade 1 and grade 2 toxicities were recorded in 7/15 and 4/15 respectively; bowel acute grade 1 and grade 2 toxicities in 4/15 and 1/15; rectal acute grade 1 and grade 2 toxicities in 3/15 and 2/15 respectively. No grade 3 or greater acute or late toxicities occurred. Biochemical control was assessed in 12/15 (80%) patients. With a median follow up of 12 months, three out of 15 patients, with biochemical relapse, showed lymph-nodal recurrence. Our early clinical results and biochemical data confirm the feasibility and show a good tolerance of the 11C choline PET guided salvage radiation therapy after HIFU failure. The findings of low acute toxicity is encouraging, but longer follow-up is needed to assess late toxicity and definitive outcomes.

Accelerated Hematopoietic Toxicity by High Energy 56Fe Radiation

PubMed Central

Datta, Kamal; Suman, Shubhankar; Trani, Daniela; Doiron, Kathryn; Rotolo, Jimmy A.; Kallakury, Bhaskar V. S.; Kolesnick, Richard; Cole, Michael F.; Fornace, Albert J.

2013-01-01

Purpose There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or x-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater. Methods C57BL/6J mice were irradiated with 56Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of 56Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival. Results Although onset was more rapid, 56Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)50/30 (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy respectively with relative biologic effectiveness for 56Fe ions of 1.25 and 1.06 for protons. Conclusions 56Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity. PMID:22077279

Cancer patients' trade-offs among efficacy, toxicity, and out-of-pocket cost in the curative and noncurative setting.

PubMed

Wong, Yu-Ning; Egleston, Brian L; Sachdeva, Kush; Eghan, Naa; Pirollo, Melanie; Stump, Tammy K; Beck, John Robert; Armstrong, Katrina; Schwartz, Jerome Sanford; Meropol, Neal J

2013-09-01

When making treatment decisions, cancer patients must make trade-offs among efficacy, toxicity, and cost. However, little is known about what patient characteristics may influence these trade-offs. A total of 400 cancer patients reviewed 2 of 3 stylized curative and noncurative scenarios that asked them to choose between 2 treatments of varying levels of efficacy, toxicity, and cost. Each scenario included 9 choice sets. Demographics, cost concerns, numeracy, and optimism were assessed. Within each scenario, we used latent class methods to distinguish groups with discrete preferences. We then used regressions with group membership probabilities as covariates to identify associations. The median age of the patients was 61 years (range, 27-90 y). Of the total number of patients included, 25% were enrolled at a community hospital, and 99% were insured. Three latent classes were identified that demonstrated (1) preference for survival, (2) aversion to high cost, and (3) aversion to toxicity. Across all scenarios, patients with higher income were more likely to be in the class that favored survival. Lower income patients were more likely to be in the class that was averse to high cost (P<0.05). Similar associations were found between education, employment status, numeracy, cost concerns, and latent class. Even in these stylized scenarios, socioeconomic status predicted the treatment choice. Higher income patients may be more likely to focus on survival, whereas those of lower socioeconomic status may be more likely to avoid expensive treatment, regardless of survival or toxicity. This raises the possibility that insurance plans with greater cost-sharing may have the unintended consequence of increasing disparities in cancer care.

Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice.

PubMed

Ting, Yuwen; Chiou, Yi-Shiou; Jiang, Yike; Pan, Min-Hsiung; Lin, Zhengyu; Huang, Qingrong

2015-08-01

Polymethoxyflavones, found widely in the peel of citrus fruits, is an emerging group of bioactive compounds with wide arrays of disease prevention functionalities. To understand the potential oral toxicity, tangeretin, being one of the most abundant polymethoxyflavones from natural sources, was used as model compound for the safety evaluation. Acute oral toxicity study was conducted using both male and female mice giving 1000, 2000, or 3000mg/kgbody weight (bw) of tangeretin in oil suspension from single gavage administration. No evidence of death was observed during 14-day post-administration period. Alterations of the hepatic cell and clinical chemistry profile increased dose dependently and exhibited distinct injury recovery pattern among different sexes. To determine the potential safety concern related to emulsification, the sub-acute toxicity of tangeretin in emulsion was evaluated and compared with un-processed oil suspension when conducting the sub-acute toxicity study over 28days. In the sub-acute study, emulsion system did not induce a significant increase of toxicity response. However, the daily low-dose application of tangeretin showed U-shaped dose-response pattern in regard to hepatic alteration. The result from this study can serve as a good safety reference for future application of polymethoxyflavone as a functional ingredient in food. Copyright © 2015 Elsevier Ltd. All rights reserved.

Outcomes Associated With 3 Treatment Schedules of High-Dose-Rate Brachytherapy Monotherapy for Favorable-Risk Prostate Cancer

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

Jawad, Maha Saada; Dilworth, Joshua T.; Gustafson, Gary S.

Purpose: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer. Methods and Materials: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0.more » The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ{sup 2} test. P values <.05 were considered significant. Results: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years. Conclusions: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer.« less

Acute sensitivity of a broad range of freshwater mussels to chemicals with different modes of toxic action

EPA Science Inventory

Freshwater mussels, one of the most imperiled groups of animals in the world, are generally underrepresented in toxicity databases used for the development of ambient water quality criteria and other environmental guidance values. Acute 96-h toxicity tests were conducted to evalu...

Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.3

EPA Science Inventory

Information on the acute toxicity to multiple species is needed for the assessment of the risks to, and the protection of, individuals, populations, and ecological communities. However, toxicity data are limited for the majority of species, while standard test species are general...

A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma

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

Krauze, Andra V.; Myrehaug, Sten D.; Chang, Michael G.

Purpose: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models. We evaluated the addition of VPA to standard radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed GBM. Methods and Materials: Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/daymore » over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment). Results: A total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis (RPA) results were significant for both OS and PFS. VPA levels were not correlated with grade 3 or 4 toxicity levels. Conclusions: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.« less

Acute recreational drug toxicity

PubMed Central

Liakoni, Evangelia; Yates, Christopher; Dines, Alison M.; Dargan, Paul I.; Heyerdahl, Fridtjof; Hovda, Knut Erik; Wood, David M.; Eyer, Florian; Liechti, Matthias E.

2018-01-01

Abstract The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity. We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project. Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively. In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives. PMID:29384873

The treatment of patients with 1-3 brain metastases: is there a place for whole brain radiotherapy alone, yet? A retrospective analysis.

PubMed

Buglione, Michela; Pedretti, Sara; Gipponi, Stefano; Buttolo, Luciano; Panciani, Paolo; Poliani, Pietro Luigi; Liserre, Roberto; Borghetti, Paolo; Pegurri, Ludovica; Costa, Loredana; Triggiani, Luca; Pasinetti, Nadia; Ghirardelli, Paolo; Pandini, Sara; Padovani, Alessandro; Magrini, Stefano Maria

2015-12-01

To evaluate the efficacy of whole brain radiotherapy (WBRT) with or without other treatments in patients (pts) with 1-3 brain metastases (BM). Toxicities and survival of 134 pts treated between 2009 and 2013 with WBRT alone (58 pts), WBRT plus surgery (SUR-WBRT: 42 pts) or WBRT followed by stereotactic or integrated boost radiotherapy (SRT-WBRT: 34 pts) were analyzed. Differences in toxicity (acute and late) incidence and in overall (OS), disease-free (DFS) and disease-specific survival (DSS) were evaluated (χ(2)-test, uni- and multivariate analysis). Pts given intensified treatments (SUR- and SBRT-WBRT) had better 3-month local response compared to WBRT alone group (p < 0.045). Better 1-year local control was evident only in SRT-WBRT pts (p < 0.035). Univariate OS analysis confirmed, as favorable prognostic factors, RPA class I (p < 0.001), GPA class III and IV (p < 0.001), single metastasis (p = 0.045), stable primary disease (p = 0.03), intensified treatment (p = 0.000), systemic therapy after radiotherapy (p = 0.04) and response of metastatic lesions (p = 0.002). At multivariate analysis, OS was better in RPA class I pts (p = 0.002), who had more aggressive radiotherapy treatments (p = 0.001), chemotherapy after radiotherapy (p < 0.001) and response to RT (p = 0.003). Response to radiotherapy (p = 0.002) and BM number (p < 0.001) resulted independently prognostic for DFS. About 60 % of patients had mild acute toxicity (G1), especially headache (51 %) and fatigue (34 %); only 2 patients (2 %) had severe (G3) headache and 5 patients (4 %) severe fatigue (G3) reversible with oral steroids. No differences were evident between the different treatment groups. Among 80 pts followed up with MRI, 12 (15 %) had leukoencephalopathy (equally distributed across subgroups) and 5 (6 %) radionecroses, 4/5 asymptomatic, 5/5 in pts given intensified treatments. This analysis confirms the known prognostic factors for BM, emphasizing the importance of intensified treatments in a population with favorable features.

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

EPA Science Inventory

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

Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish

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

Fuse, Yuji; Nguyen, Vu Thanh; Kobayashi, Makoto, E

Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a{sup fh318}. After treatment with 1 mM sodium arsenite, the survival of nrf2a{sup fh318} larvae was significantly shortermore » than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity. - Highlights: • The role of Nrf2 under arsenite exposure was valuated using zebrafish. • Nrf2 mutant zebrafish was highly sensitive to acute arsenic toxicity. • Nrf2 induced anti-arsenic genes in response to arsenite. • Sulforaphane attenuated arsenic toxicity through Nrf2 activation. • Nrf2 system plays an important role in the defense against acute arsenic toxicity.« less

Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

USGS Publications Warehouse

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

1982-01-01

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

Intensity-Modulated Radiation Therapy for Anal Malignancies: A Preliminary Toxicity and Disease Outcomes Analysis

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

Pepek, Joseph M.; Willett, Christopher G.; Wu, Q. Jackie

Purpose: Intensity-modulated radiation therapy (IMRT) has the potential to reduce toxicities associated with chemoradiotherapy in the treatment of anal cancer. This study reports the results of using IMRT in the treatment of anal cancer. Methods and Materials: Records of patients with anal malignancies treated with IMRT at Duke University were reviewed. Acute toxicity was graded using the NCI CTCAEv3.0 scale. Overall survival (OS), metastasis-free survival (MFS), local-regional control (LRC) and colostomy-free survival (CFS) were calculated using the Kaplan-Meier method. Results: Forty-seven patients with anal malignancy (89% canal, 11% perianal skin) were treated with IMRT between August 2006 and September 2008.more » Median follow-up was 14 months (19 months for SCC patients). Median radiation dose was 54 Gy. Eight patients (18%) required treatment breaks lasting a median of 5 days (range, 2-7 days). Toxicity rates were as follows: Grade 4: leukopenia (7%), thrombocytopenia (2%); Grade 3: leukopenia (18%), diarrhea (9%), and anemia (4%); Grade 2: skin (93%), diarrhea (24%), and leukopenia (24%). The 2-year actuarial overall OS, MFS, LRC, and CFS rates were 85%, 78%, 90% and 82%, respectively. For SCC patients, the 2-year OS, MFS, LRC, and CFS rates were 100%, 100%, 95%, and 91%, respectively. Conclusions: IMRT-based chemoradiotherapy for anal cancer results in significant reductions in normal tissue dose and acute toxicities versus historic controls treated without IMRT, leading to reduced rates of toxicity-related treatment interruption. Early disease-related outcomes seem encouraging. IMRT is emerging as a standard therapy for anal cancer.« less

Epidemics of mold poisoning past and present.

PubMed

Meggs, William J

2009-01-01

Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

Comparative acute toxicity of neonicotinoid and pyrethroid insecticides to non-target crayfish (Procambarus clarkii) associated with rice-crayfish crop rotations.

PubMed

Barbee, Gary C; Stout, Michael J

2009-11-01

Most insecticides used to control rice water weevil (Lissorhoptrus oryzophilus Kuscel) infestations are pyrethroids. However, pyrethroids are highly toxic to non-target crayfish associated with rice-crayfish crop rotations. One solution to the near-exclusive reliance on pyrethroids in a rice-crayfish pest management program is to incorporate neonicotinoid insecticides, which are insect specific and effective against weevils but not extremely toxic to crayfish. This study aimed to take the first step to assess neonicotinoids as alternatives to pyrethroids in rice-crayfish crop rotations by measuring the acute toxicities of three candidate neonicotinoid insecticides, clothianidin, dinotefuran and thiamethoxam, to juvenile Procambarus clarkii (Girard) crayfish and comparing them with the acute toxicities of two currently used pyrethroid insecticides, lambda-cyhalothrin and etofenprox. Neonicotinoid insecticides are at least 2-3 orders of magnitude less acutely toxic (96 h LC(50)) than pyrethroids to juvenile Procambarid crayfish: lambda-cyhalothrin (0.16 microg AI L(-1)) = etofenprox (0.29 microg AI L(-1)) > clothianidin (59 microg AI L(-1)) > thiamethoxam (967 microg AI L(-1)) > dinotefuran (2032 microg AI L(-1)). Neonicotinoid insecticides appear to be much less hazardous alternatives to pyrethroids in rice-crayfish crop rotations. Further field-level neonicotinoid acute and chronic toxicity testing with crayfish is needed. (c) 2009 Society of Chemical Industry.

Acute and subacute toxicity of Schinus terebinthifolius bark extract.

PubMed

Lima, L B; Vasconcelos, C F B; Maranhão, H M L; Leite, V R; Ferreira, P A; Andrade, B A; Araújo, E L; Xavier, H S; Lafayette, S S L; Wanderley, A G

2009-12-10

Schinus terebinthifolius Raddi (Anacardiaceae) has long been used in traditional Brazilian medicine, especially to treat inflammatory and haemostatic diseases. The objective of this study was to evaluate the acute and subacute toxicity (45 days) of Schinus terebinthifolius via the oral route in Wistar rats of both sexes. For the acute toxicity test, the dried extract of Schinus terebinthifolius bark was administered in doses from 0.625 to 5.0 g/kg (n=5/group/sex) and in the subacute toxicity test the following doses were used: 0.25, 0.625 and 1.5625 g/kg/day (n=13/group/sex), for 45 consecutive days. In the acute toxicity test, Schinus terebinthifolius did not produce any toxic signs or deaths. The subacute treatment with Schinus terebinthifolius did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups, except in two male groups, in which the treatment with Schinus terebinthifolius (0.25 and 0.625 g/kg) induced an increase of mean corpuscular volume values (2.9 and 2.6%, respectively). These variations are within the physiological limits described for the specie and does not have clinical relevance. The acute and subacute administration of the dried extract of Schinus terebinthifolius bark did not produced toxic effects in Wistar rats.

Dose to organs at risk in the upper abdomen in patients treated with extended fields by helical tomotherapy: a dosimetric and clinical preliminary study.

PubMed

Bresciani, Sara; Garibaldi, Elisabetta; Cattari, Gabriella; Maggio, Angelo; Di Dia, Amalia; Delmastro, Elena; Gabriele, Domenico; Stasi, Michele; Gabriele, Pietro

2013-10-25

The aim of this work was to determine the technical feasibility and safety of extended-field radiotherapy (EF), performed by Helical TomoTherapy, in patients with positive pelvic and/or para-aortic nodes. Dosimetric data were collected and acute and sub-acute toxicities of the upper abdominal organs at risk (OAR) were evaluated. Twenty-nine patients suitable for EF irradiation for local disease and/or nodal disease in the pelvic or para-aortic area were treated. The prescription dose was 50.4/54 Gy (1.7-1.8 Gy/fraction) for prophylactic lymph nodes (N-) and 60-70.5 Gy (2-2.35 Gy/fraction) for clinically evident gross disease (N+). Modulation factor (MF), pitch and field width (FW) were chosen to optimize dose distribution and treatment duration. Dose values of PTVs and OAR were analysed. The length of the treatment field, the N + and N- volumes, and treatment duration were reported. To evaluate the safety of treatment, haematological, hepatic, renal and pancreatic functions were assessed before, during and after treatment. The median follow-up time was 17.6 months (range: 6-22 months). The treatment was well tolerated and all patients but one completed treatment without interruption. Four of the 29 patients experienced G3 haematological acute toxicity (13.8%), but no patient experienced sub-acute grade G3 toxicity. Ten patients experienced G1 and three G2 acute gastrointestinal toxicity (nausea). No sub-acute gastrointestinal or renal toxicity was observed. Only one (3.7%) patient had a persistent slight increase of pancreatic enzymes and two (7.4%) patients a slight increase of hepatic enzymes six months after radiotherapy (G1 toxicity). With our treatment design and dose regimen, we found that EF treatment by TomoTherapy could be safely and effectively delivered with minimal acute and sub-acute toxicities in the upper abdomen area.

Characterization of the dinophysistoxin-2 acute oral toxicity in mice to define the Toxicity Equivalency Factor.

PubMed

Abal, Paula; Louzao, M Carmen; Cifuentes, José Manuel; Vilariño, Natalia; Rodriguez, Ines; Alfonso, Amparo; Vieytes, Mercedes R; Botana, Luis M

2017-04-01

Ingestion of shellfish with dinophysistoxin-2 (DTX2) can lead to diarrheic shellfish poisoning (DSP). The official control method of DSP toxins in seafood is the liquid chromatography-mass spectrometry analysis (LC-MS). However in order to calculate the total toxicity of shellfish, the concentration of each compound must be multiplied by individual Toxicity Equivalency Factor (TEF). Considering that TEFs caused some controversy and the scarce information about DTX2 toxicity, the aim of this study was to characterize the oral toxicity of DTX2 in mice. A 4-Level Up and Down Procedure allowed the characterization of DTX2 effects and the estimation of DTX2 oral TEF based on determination of the lethal dose 50 (LD50). DTX2 passed the gastrointestinal barrier and was detected in urine and feces. Acute toxicity symptoms include diarrhea and motionless, however anatomopathology study and ultrastructural images restricted the toxin effects to the gastrointestinal tract. Nevertheless enterocytes microvilli and tight junctions were not altered, disconnecting DTX2 diarrheic effects from paracellular epithelial permeability. This is the first report of DTX2 oral LD 50 (2262 μg/kg BW) indicating that its TEF is about 0.4. This result suggests reevaluation of the present TEFs for the DSP toxins to better determine the actual risk to seafood consumers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intravenous versus intramuscular cobinamide compared to intravenous saline (control) in the treatment of acute, survivable, hydrogen sulfide toxicity in swine (Sus Scrofa).

DTIC Science & Technology

2017-11-09

FWH20140070A, “Intravenous versus intramuscular // compared to intravenous saline ( control ) in the treatment of acute, survivable, hydrogen sulfide toxicity... control ) in the treatment of acute, survivable, hydrogen sulfide toxicity in swine (Sus Scrofa). 4. Principal Investigator (PI): Name Rank Date...remainder of the study. Animals were treated with IV HOC, IV Cobinamide or control (no treatment) 1 minute post apnea. There were no significant

Hyper-alkalinization without hyper-hydration for the prevention of high-dose methotrexate acute nephrotoxicity in patients with osteosarcoma.

PubMed

Mir, Olivier; Ropert, Stanislas; Babinet, Antoine; Alexandre, Jérôme; Larousserie, Frédérique; Durand, Jean-Philippe; Enkaoua, Eric; Anract, Philippe; Goldwasser, François

2010-11-01

To evaluate the reliability and renal safety of an original schedule of high-dose methotrexate (HDMTX) administration with hyper-alkalinization, and without hyper-hydration. Patients with osteosarcoma received HDMTX (8-12 g/m(2)) as a 4-h infusion. Hypertonic 8.4% sodium bicarbonate was infused prior to HDMTX, then once daily for 3 days. Methotrexate serum concentrations were measured at hour 4 (Cmax), hour 24, hour 48, and hour 72. Urinary pH was measured on each miction. Serum creatinine was assessed on days 1, 3, and 8. Twenty-six patients (median age: 18 years, range: 15-25) received a total of 344 cycles of HDMTX, including 16 patients treated in an outpatient basis. Urinary pH remained constantly higher than 7.5 in all patients. Grade 1 creatininemia toxicity was observed in 31 cycles (9%), and grade 2 creatinine toxicity was observed in one patient. No episode of acute severe nephrotoxicity was observed. No significant worsening was observed in serum creatinine and calculated creatinine clearance from baseline to the end of therapy (P = 0.74). The main extra-renal toxicity was alkalinization-related hypokalemia from H48. No re-hospitalization was required. Hyper-alkalinization appears an efficient and reliable method to prevent the acute renal toxicity of HDMTX and allows its safe administration in the outpatient setting.

Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration

PubMed Central

Selwood, Andrew I.; Waugh, Craig; Harwood, David T.; Rhodes, Lesley L.; Reeve, John; Sim, Jim; Munday, Rex

2017-01-01

Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as “Toxicity Equivalence Factors” (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health. PMID:28230783

The effect of aerobic exercise on treatment-related acute toxicity in men receiving radical external beam radiotherapy for localised prostate cancer.

PubMed

Kapur, G; Windsor, P M; McCowan, C

2010-09-01

We retrospectively analysed acute radiation toxicity data for patients who had participated in a randomised controlled study in our centre in order to assess the impact of aerobic exercise on acute rectal and bladder morbidity during treatment. Data from 65 of 66 patients were analysed: 33 allocated into a control group (standard advice) and 33 into an exercise group (aerobic walking for 30 min at least three times per week) during 4 weeks of external beam radiotherapy; one patient in the exercise group withdrew after randomisation before starting radiotherapy. There was a trend towards less severe acute rectal toxicity in the exercise group with a statistically significant difference in mean toxicity scores over the 4 weeks of radiotherapy (P=0.004), with no significant difference in bladder toxicity scores between the two groups (P=0.123). The lack of an association for severity of bladder toxicity could be attributed to the confounding effect of lower urinary tract symptoms from their prostate cancer. Keeping active and being asked to adhere to a well-defined exercise schedule appears to reduce the severity of rectal toxicity during radiotherapy to the prostate.

Predicting adult fish acute lethality with the zebrafish embryo: relevance of test duration, endpoints, compound properties, and exposure concentration analysis.

PubMed

Knöbel, Melanie; Busser, Frans J M; Rico-Rico, Angeles; Kramer, Nynke I; Hermens, Joop L M; Hafner, Christoph; Tanneberger, Katrin; Schirmer, Kristin; Scholz, Stefan

2012-09-04

The zebrafish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, which is required by various regulations for environmental risk assessment of chemicals. We investigated the reliability of the embryo test by probing organic industrial chemicals with a wide range of physicochemical properties, toxicities, and modes of toxic action. Moreover, the relevance of using measured versus nominal (intended) exposure concentrations, inclusion of sublethal endpoints, and different exposure durations for the comparability with reported fish acute toxicity was explored. Our results confirm a very strong correlation of zebrafish embryo to fish acute toxicity. When toxicity values were calculated based on measured exposure concentrations, the slope of the type II regression line was 1 and nearly passed through the origin (1 to 1 correlation). Measured concentrations also explained several apparent outliers. Neither prolonged exposure (up to 120 h) nor consideration of sublethal effects led to a reduced number of outliers. Yet, two types of compounds were less lethal to embryos than to adult fish: a neurotoxic compound acting via sodium channels (permethrin) and a compound requiring metabolic activation (allyl alcohol).

Continuous in vitro exposure of intestinal epithelial cells to E171 food additive causes oxidative stress, inducing oxidation of DNA bases but no endoplasmic reticulum stress.

PubMed

Dorier, Marie; Béal, David; Marie-Desvergne, Caroline; Dubosson, Muriel; Barreau, Frédérick; Houdeau, Eric; Herlin-Boime, Nathalie; Carriere, Marie

2017-08-01

The whitening and opacifying properties of titanium dioxide (TiO 2 ) are commonly exploited when it is used as a food additive (E171). However, the safety of this additive can be questioned as TiO 2 nanoparticles (TiO 2 -NPs) have been classed at potentially toxic. This study aimed to shed some light on the mechanisms behind the potential toxicity of E171 on epithelial intestinal cells, using two in vitro models: (i) a monoculture of differentiated Caco-2 cells and (ii) a coculture of Caco-2 with HT29-MTX mucus-secreting cells. Cells were exposed to E171 and two different types of TiO 2 -NPs, either acutely (6-48 h) or repeatedly (three times a week for 3 weeks). Our results confirm that E171 damaged these cells, and that the main mechanism of toxicity was oxidation effects. Responses of the two models to E171 were similar, with a moderate, but significant, accumulation of reactive oxygen species, and concomitant downregulation of the expression of the antioxidant enzymes catalase, superoxide dismutase and glutathione reductase. Oxidative damage to DNA was detected in exposed cells, proving that E171 effectively induces oxidative stress; however, no endoplasmic reticulum stress was detected. E171 effects were less intense after acute exposure compared to repeated exposure, which correlated with higher Ti accumulation. The effects were also more intense in cells exposed to E171 than in cells exposed to TiO 2 -NPs. Taken together, these data show that E171 induces only moderate toxicity in epithelial intestinal cells, via oxidation.

Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats.

PubMed

Al-Afifi, Nashwan Abdullah; Alabsi, Aied Mohammed; Bakri, Marina Mohd; Ramanathan, Anand

2018-02-05

Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. This study demonstrates tolerability of DC resin methanol extract administered daily for 28 days up to 1500 mg/kg dose.

Acute toxic hepatitis caused by an aloe vera preparation in a young patient: a case report with a literature review.

PubMed

Lee, Jeonghun; Lee, Mi Sun; Nam, Kwan Woo

2014-07-01

Aloe is one of the leading products used in phytomedicine. Several cases of aloe-induced toxic hepatitis have been reported in recent years. However, its toxicology has not yet been systematically described in the literature. A 21-year-old female patient was admitted to our hospital with acute hepatitis after taking an aloe vera preparation for four weeks. Her history, clinical manifestation, laboratory findings, and histological findings all led to the diagnosis of aloe vera-induced toxic hepatitis. We report herein on a case of acute toxic hepatitis induced by aloe vera.

Comparative Toxicity of Eight Oil Dispersants, Louisiana Sweet Crude Oil (LSC) and Chemically Dispersed LSC to Two Aquatic Test Species

EPA Science Inventory

This study describes the acute toxicity of eight commercial oil dispersants, Louisiana sweet crude oil (LSC), and chemically dispersed LSC. The approach utilized consistent test methodologies within a single laboratory in assessing the relative acute toxicity of the eight dispers...

Environmental Sentinel Biomonitor (ESB) System Technology Assessment

DTIC Science & Technology

2007-02-01

Andersson M, Barile FA, et al. 1996. MEIC evaluation of acute systemic toxicity Part I. Methodology of 68 in vitro toxicity assays used to test the first...30 reference chemicals. ATLA 24:251-272. Clemedson C, Andersson M, Aoki Y, Barile FA, et al. 1998. MEIC evaluation of acute systemic toxicity Part IV

Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species

EPA Science Inventory

The authors developed a toxicity database for unionid mussels to examine the extent of intra- and interlaboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the 2 life stages; and the variation in se...

The acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ionic liquids on Chlorella vulgaris and Daphnia magna.

PubMed

Zhang, Cheng; Zhang, Shuai; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Zhou, Tongtong

2017-10-01

Given their increasingly widespread application, the toxic effects of ionic liquids (ILs) have become the subject of significant attention in recent years. Therefore, the present study assessed the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ([C n mim]NO 3 (n = 2, 4, 6, 8, 10, 12)) on Chlorella vulgaris and Daphnia magna. The sensitivity of the tested organism Daphnia magna and the investigated IL concentrations in water using high-performance liquid chromatography (HPLC) were also evaluated to demonstrate the reliability of the present study. The results illustrated that Daphnia magna is indeed sensitive to the reference toxicant and the investigated ILs were stable in the aquatic environment. The 50% effect concentration (EC 50 ) was used to represent the acute toxic effects on Chlorella vulgaris and Daphnia magna. With the increasing alkyl-chain lengths, the toxicity of the investigated ILs increased in both the test organisms. Accordingly, the alkyl-chain lengths can cause significantly toxic effects on aquatic organisms, and Daphnia magna are much more sensitive than Chlorella vulgaris to the imidazolium-based ILs used in the present study. Furthermore, the present study provides more information on the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mometasone Furoate Effect on Acute Skin Toxicity in Breast Cancer Patients Receiving Radiotherapy: A Phase 3 Double-Blind, Randomized Trial from the North Central Cancer Treatment Group N06C4

PubMed Central

Miller, Robert C.; Schwartz, David J.; Sloan, Jeff A.; Griffin, Patricia C.; Deming, Richard L.; Anders, Jon C.; Stoffel, Thomas J.; Haselow, Robert E.; Schaefer, Paul L.; Bearden, James D.; Atherton, Pamela J.; Loprinzi, Charles L.; Martenson, James A.

2010-01-01

Purpose A 2-arm, double-blinded, randomized trial to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. Methods and Materials Patients with ductal carcinoma in situ or invasive breast carcinoma receiving external beam radiotherapy to breast or chest wall were randomly assigned to daily apply 0.1% MMF or placebo cream. Primary study end point was provider-assessed maximum grade of Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 radiation dermatitis. Secondary end points included provider-assessed CTCAE grade 3 or greater radiation dermatitis and adverse-event monitoring. Patient-reported outcome (PRO) measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and quality of life self-assessment. Assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. Results In total, 176 patients were enrolled from September 21, 2007 through December 7, 2007. The provider-assessed primary end point showed no difference in mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs 1.3 for placebo; P=.18). CTCAE toxicity was greater in placebo group (P=.04), primarily from pruritus. For PRO measures, the maximum Skindex-16 score for MMF group showed less itching (P=.008), less irritation (P=.01), less symptom persistence or recurrence (P=.02), and less annoyance with skin problems (P=.04); the group's maximum Skin Toxicity Assessment Tool score showed less burning sensation (P=.02) and less itching (P=.002). Conclusion Patients receiving daily MMF during radiotherapy may experience reduced acute skin toxicity in comparison to placebo. PMID:20800381

High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

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

Zamboglou, Nikolaos; Tselis, Nikolaos, E-mail: ntselis@hotmail.com; Baltas, Dimos

2013-03-01

Purpose: To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. Methods and Materials: Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy,more » using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. Results: The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. Conclusion: Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.« less

Phytochemistry, Brine shrimp lethality and mice acute oral toxicity studies on seed extracts of Vernonia anthelmintica.

PubMed

Jamil, Subia; Khan, Rafeeq Alam; Afroz, Syeda; Ahmed, Shadab

2016-11-01

Despite the widespread use of Vernonia anthelmintica seeds in traditional medicine, the need to establish the safety of the Vernonia anthelmintica is required to ascertain the safe use of this herbal medicine. The aim of the present study is to establish the acute toxicity profile of different extracts of Vernonia anthelmintica. Hexane and ethanol extract of Vernonia Anthelmintica has been studied for its brine shrimp lethality potential. Water decoction (WDVA), Hexane (HEVA) and Ethanol (EEVA) extracts of Vernonia anthelmintica has also been evaluated for their in-vivo acute oral toxicity in mice by Lorke's method. Phytochemistry of all three extracts was also evaluated for the presence of their secondary metabolites. All three extracts showed the presence of flavonoids and terpenoids, while alkaloids, tannins and fixed oils were present in HEVA and EEVA. Furthermore EEVA also showed presence of carbohydrates and HEVA also showed the presence of cardiac glycosides. Ethanol and hexane extracts of Vernonia anthelmintica showed a positive cytotoxicity in brine shrimp lethality test at 24 hours with LC50 104.16 (224.0-48.05)μg/ml and 216.11μg/ml (378.2-128.7) respectively as compared to standard drug etoposide LC50 7.46μg/ml. The oral LD50 for EEVA, HEVA and WDVA in mice by Lorke's method was greater than 5000mg/kg. The result of brine shrimp lethality test clearly exhibited the presence of bioactive compounds with cytotoxic potential; however seems to be safe for oral use since LD50 was higher than 5000mg/kg and thus safety of acute dosing in vivo practices is justified.

New EPA Guidance for Testing Pesticides Will Reduce Animal Testing

EPA Pesticide Factsheets

EPA is issuing guidance for requesting waivers of acute dermal toxicity testing requirements for pesticide formulations, which will lead to fewer animal tests for acute dermal toxicity for pesticides.

The effect of pH on the toxicity of fatty acids and fatty acid amides to rainbow trout gill cells.

PubMed

Bertin, Matthew J; Voronca, Delia C; Chapman, Robert W; Moeller, Peter D R

2014-01-01

Harmful algal blooms (HABs) expose aquatic organisms to multiple physical and chemical stressors during an acute time period. Algal toxins themselves may be altered by water chemistry parameters affecting their bioavailability and resultant toxicity. The purpose of this study was to determine the effects of two abiotic parameters (pH, inorganic metal salts) on the toxicity of fatty acid amides and fatty acids, two classes of lipids produced by harmful algae, including the golden alga, Prymnesium parvum, that are toxic to aquatic organisms. Rainbow trout gill cells were used as a model of the fish gill and exposed to single compounds and mixtures of compounds along with variations in pH level and concentration of inorganic metal salts. We employed artificial neural networks (ANNs) and standard ANOVA statistical analysis to examine and predict the effects of these abiotic parameters on the toxicity of fatty acid amides and fatty acids. Our results demonstrate that increasing pH levels increases the toxicity of fatty acid amides and inhibits the toxicity of fatty acids. This phenomenon is reversed at lower pH levels. Exposing gill cells to complex mixtures of chemical factors resulted in dramatic increases in toxicity compared to tests of single compounds for both the fatty acid amides and fatty acids. These findings highlight the potential of physicochemical factors to affect the toxicity of chemicals released during algal blooms and demonstrate drastic differences in the effect of pH on fatty acid amides and fatty acids. Published by Elsevier B.V.

Principals Of Radiation Toxicology: Important Aspects.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

“All things are poison, and nothing is without poison; only the dose permits something not to be poisonous.” Paracelsus Key Words: Radiation Toxins (RT), Radiation Toxicants (RTc), Radiation Poisons (RP), Radiation Exposure (RE), Radiation Toxicology is the science about radiation poisons. [D.Popov et al. 2012,J.Zhou et al. 2007,] Radiation Toxins is a specific proteins with high enzymatic activity produced by living irradiated mammals. [D.Popov et al. 2012,] Radiation Toxicants is a substances that produce radiomimetics effects, adverse biological effects which specific for radiation. [D.Popov et al. 2012,] Radiation Toxic agent is specific proteins that can produce pathological biological effects specific for physical form of radiation.[D.Popov et al. 1990,2012,V. Maliev 2007] Different Toxic Substances isolated from cells or from blood or lymph circulation. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007,] Radiation Toxins may affects many organs or specific organ, tissue, specific group of cells. [Kudriashov I. et al. 1970, D.Popov et al. 1990,2012,V. Maliev et al. 2007] For example: Radiation Toxins could induce collective toxic clinical states to include: systemic inflammatory response syndrome (SIRS),toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMODS),and finally, toxic multiple organ failure (TMOF). [T. Azizova et al. 2005, Konchalovsky et al., 2005, D. Popov et al 2012] However, Radiation Toxins could induce specific injury of organs or tissue and induce Acute Radiation Syndromes such as Acute Radiation Cerebrovascular Syndrome, Acute Radiation Cardiovascular Syndrome, Acute Radiation Hematopoietic Syndrome, Acute Radiation GastroIntestinal Syndrome. [ D.Popov et al. 1990, 2012, V. Maliev et al. 2007] Radiation Toxins correlates with Radiation Exposure and the dose-response relationship is a fundamental and essential concept in classic Toxicology and Radiation Toxicology.[ D.Popov et al. 1990, 2012] Moderate and high doses of radiation induces necrosis of radiosensitive cells with the subsequent formation of radiation toxins and their induced acute inflammatory processes. Radiation necrosis is the most substantial and most severe form of radiation induced injury, and when widespread, has grave therapeutic implications. [D. Popov et al. 1990, 2012,Claudio A. et al. 2002, Robertson J. et al. 2002, ] Relatively small doses of Radiation Toxins induce apoptosis and high doses of Radiation Toxins induce necrosis. [Rastogi P. et al. 2009, D. Popov et al. 1990, 2012,] Threshold of Toxic Effects occurs and can be defined. [D. Popov et al. 2012, ] Radiation Toxins affects Somatic cells and Germ Cells. Radiation Toxins can induce teratogenic processes. Specific Toxicity of Radiation Toxins can affects developing fetus. Material and Methods, Results: http://www.intechopen.com/books/current-topics-in-ionizing-radiation-research/radiation-toxins-molecular-mechanisms-of-toxicity-and-radiomimetic-properties- Conclusion: Radiation is a physical agent - induce activation of some secretory proteins with high enzymatic activity. This proteins called as Radiation Toxins can produce specific for radiation biological and toxic effects after administration to radiation naive mammals. [V. Maliev et al. 2007, D. Popov et al. 1990, 2012] Radiation Toxins are teratogenic and oncogenic. Radiation Toxins effects depend on Administered Dose and Radiation effects depend on Exposure Dose and Absorbed Dose. The levels of Radiation Toxins correlates with Radiation Exposure.

Comparative study of toxicity of azo dye Procion Red MX-5B following biosorption and biodegradation treatments with the fungi Aspergillus niger and Aspergillus terreus.

PubMed

Almeida, E J R; Corso, C R

2014-10-01

Azo dyes are an important class of environmental contaminants and are characterized by the presence of one or more azo bonds (-N=N-) in their molecular structure. Effluents containing these compounds resist many types of treatments due to their molecular complexity. Therefore, alternative treatments, such as biosorption and biodegradation, have been widely studied to solve the problems caused by these substances, such as their harmful effects on the environment and organisms. The aim of the present study was to evaluate biosorption and biodegradation of the azo dye Procion Red MX-5B in solutions with the filamentous fungi Aspergillus niger and Aspergillus terreus. Decolorization tests were performed, followed by acute toxicity tests using Lactuca sativa seeds and Artemia salina larvae. Thirty percent dye removal of the solutions was achieved after 3 h of biosorption. UV-Vis spectroscopy revealed that removal of the dye molecules occurred without major molecular changes. The acute toxicity tests confirmed lack of molecular degradation following biosorption with A. niger, as toxicity to L. sativa seed reduced from 5% to 0%. For A. salina larvae, the solutions were nontoxic before and after treatment. In the biodegradation study with the fungus A. terreus, UV-Vis and FTIR spectroscopy revealed molecular degradation and the formation of secondary metabolites, such as primary and secondary amines. The biodegradation of the dye molecules was evaluated after 24, 240 and 336 h of treatment. The fungal biomass demonstrated considerable affinity for Procion Red MX-5B, achieving approximately 100% decolorization of the solutions by the end of treatment. However, the solutions resulting from this treatment exhibited a significant increase in toxicity, inhibiting the growth of L. sativa seeds by 43% and leading to a 100% mortality rate among the A. salina larvae. Based on the present findings, biodegradation was effective in the decolorization of the samples, but generated toxic metabolites, while biosorption was effective in both decolorization and reducing the toxicity of the solutions. Published by Elsevier Ltd.

Grouped gene selection and multi-classification of acute leukemia via new regularized multinomial regression.

PubMed

Li, Juntao; Wang, Yanyan; Jiang, Tao; Xiao, Huimin; Song, Xuekun

2018-05-09

Diagnosing acute leukemia is the necessary prerequisite to treating it. Multi-classification on the gene expression data of acute leukemia is help for diagnosing it which contains B-cell acute lymphoblastic leukemia (BALL), T-cell acute lymphoblastic leukemia (TALL) and acute myeloid leukemia (AML). However, selecting cancer-causing genes is a challenging problem in performing multi-classification. In this paper, weighted gene co-expression networks are employed to divide the genes into groups. Based on the dividing groups, a new regularized multinomial regression with overlapping group lasso penalty (MROGL) has been presented to simultaneously perform multi-classification and select gene groups. By implementing this method on three-class acute leukemia data, the grouped genes which work synergistically are identified, and the overlapped genes shared by different groups are also highlighted. Moreover, MROGL outperforms other five methods on multi-classification accuracy. Copyright © 2017. Published by Elsevier B.V.

A comparative analysis of acute-phase proteins as inflammatory biomarkers in preclinical toxicology studies: implications for preclinical to clinical translation.

PubMed

Watterson, Claire; Lanevschi, Anne; Horner, Judith; Louden, Calvert

2009-01-01

Recently, in early clinical development, a few biologics and small molecules intended as antitumor or anti-inflammatory agents have caused a severe adverse pro-inflammatory systemic reaction also known as systemic inflammatory response syndrome (SIRS). This toxicity could result from expected pharmacological effects of a therapeutic antibody and/or from interaction with antigens expressed on cells/tissues other than the intended target. Clinical monitoring of SIRS is challenging because of the narrow diagnostic window to institute a successful intervening therapeutic strategy prior to acute circulatory collapse. Furthermore, for these classes of therapeutic agents, studies in animals have low predictive ability to identify potential human hazards. In vitro screens with human cells, though promising, need further development. Therefore, identification of improved preclinical diagnostic markers of SIRS will enable clinicians to select applicable markers for clinical testing and avoid potentially catastrophic events. There is limited preclinical toxicology data describing the interspecies performance of acute-phase proteins because the response time, type, and duration of major acute-phase proteins vary significantly between species. This review will attempt to address this intellectual gap, as well as the use and applicability of acute-phase proteins as preclinical to clinical translational biomarkers of SIRS.

Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study.

PubMed

Franco, Pierfrancesco; Potenza, Ilenia; Moretto, Francesco; Segantin, Mattia; Grosso, Mario; Lombardo, Antonello; Taricco, Daniela; Vallario, Patrizia; Filippi, Andrea Riccardo; Rampino, Monica; Ricardi, Umberto

2014-12-29

Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery. The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.

Toxicity evaluation of the process effluent streams of a petrochemical industry.

PubMed

Reis, J L R; Dezotti, M; Sant'Anna, G L

2007-02-01

The physico-chemical characteristics and the acute toxicity of several wastewater streams, generated in the industrial production of synthetic rubber, were determined. The acute toxicity was evaluated in bioassays using different organisms: Danio rerio (fish), Lactuca sativa (lettuce) and Brachionus calyciflorus (rotifer). The removal of toxicity attained in the industrial wastewater treatment plant was also determined upstream and downstream of the activated sludge process. The results obtained indicate that the critical streams in terms of acute toxicity are the effluents from the liquid polymer unit and the spent caustic butadiene washing stage. The biological treatment was able to partially remove the toxicity of the industrial wastewater. However, a residual toxicity level persisted in the biotreated wastewater. The results obtained with Lactuca sativa showed a high degree of reproducibility, using root length or germination index as evaluation parameters. The effect of volatile pollutants on the toxicity results obtained with lettuce seeds was assessed, using ethanol as a model compound. Modifications on the assay procedure were proposed. A strong correlation between the toxic responses of Lactuca sativa and Danio rerio was observed for most industrial effluent streams.

Single Nucleotide Polymorphism TGFβ1 R25P Correlates with Acute Toxicity during Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients

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

Smith, J. Joshua; Wasserman, Isaac; Icahn School of Medicine at Mount Sinai, New York, New York

Purpose: To validate the finding of an association between single nucleotide polymorphisms (SNPs) and toxicity during chemoradiotherapy (CRT) in rectal cancer patients, in an independent population. Methods and Materials: The cohort consisted of 165 patients who received CRT for rectal cancer from 2006 to 2012. Prospectively recorded toxicity information, graded according to the Common Terminology Criteria for Adverse Events version 3.0, was retrieved from the medical record. Additionally, a subset of 52 patients recorded their gastrointestinal symptoms weekly during CRT, using the 7-item Bowel Problems Scale. Deoxyribonucleic acid was extracted from normal tissue in the proctectomy specimens and screened for 3more » SNPs: XRCC1 R399Q, XPD K751Q, and TGFβ1 R25P. Univariable and multivariable logistic regression models were constructed. Results: The median radiation dose was 50.4 Gy, and all patients received concurrent chemotherapy. Toxicities measured by the Common Terminology Criteria for Adverse Events were closely associated with patient-reported outcomes for the patients who completed the 7-item Bowel Problems Scale. Grade ≥3 toxicity occurred during CRT in 14 patients (8%). All 14 patients had either XRCC1 R399Q or TGFβ1 R25P polymorphisms. The TGFβ1 R25P polymorphism was significantly associated with grade ≥3 toxicity (odds ratio [OR] 3.47, P=.04) and, in patients who completed the Bowel Problems Scale, with grade ≥4 toxicity (OR 5.61, P=.02). The latter finding persisted in a multivariable logistic regression model controlling for ethnicity, age, and sex (adjusted OR 1.83, P=.02). Conclusions: We have validated the correlation between the TGFβ1 R25P SNP and acute toxicity during CRT in an independent cohort using both clinician- and patient-reported toxicity. The information from our study could be used as a basis to formulate a prospective trial testing the utility of this SNP as a biomarker of acute toxicity during neoadjuvant treatment in locally advanced rectal cancer.« less

Acute and chronic effects of heavy metals and cyanide on Mysidopsis bahia (crustacea:mysidacea)

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

Lussier, S.M.; Gentile, J.H.; Walker, J.

1985-01-01

Acute and whole life-cycle toxicity tests were conducted with the estuarine mysid shrimp, Mysidopsis bahia, exposed to cyanide and selected heavy metals. Acute toxicity values (96h LC50) ranged from 3.5 micrograms/1 for mercury to 3130 micrograms/1 for lead, and were ranked in order of toxicity: (greatest)Hg, Cd, Cu, Cn, Ag, Sn, Ni, As, Cr, and Pb(least). The chronic toxicity values ranged from 1.2 micrograms/1 for mercury to 893 micrograms/1 for arsenic. Chronic values were calculated from either survival, time to first reproduction, or number of young produced. When acute toxicity data for the same chemical are compared, M. bahia ismore » consistently among the more sensitive marine species. Lack of comparable data precludes a similar observation with chronic tests. Examination of the relative sensitivity of the chronic responses indicates that only for cadmium was survival more sensitive than reproduction.« less

Vaginal Toxic Shock Reaction Triggering Desquamative Inflammatory Vaginitis

PubMed Central

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

2012-01-01

Objective To report two cases of desquamative inflammatory vaginitis (DIV) associated with toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus strains. Materials and Methods Case report of two patients, one with an acute and one with a chronic presentation, diagnosed with DIV on the basis of clinical findings and wet mount microscopy. Pre- and posttreatment vaginal bacterial and yeast cultures were obtained. Results Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial cultures following oral antibiotic therapy were negative. Conclusions DIV may be triggered through TSST-1-mediated vaginal toxic shock reaction. PMID:23222054

PCP and hallucinogens.

PubMed

Carroll, M E

1990-01-01

In this review phencyclidine and related arylcyclohexylamines and hallucinogens, using LSD as the prototype, are considered as two distinct classes of abused drugs. Within these classes drugs that are found on the street are discussed, and a current epidemiological summary is provided. The abuse liability and dependence potential of these drugs are evaluated by considering four major determinants of their abuse. First, is the ability of a drug to function as a positive reinforcer and increase the probability of operant behavior leading to its delivery. Animal data describing the reinforcing effects of PCP are reviewed with respect to the influence of variables controlling drug-reinforced behavior; however, there are no animal models of hallucinogen-reinforced behavior. Several methods of quantifying reinforcing efficacy are discussed. A second determinant is the subjective effects of the respective drugs. These effects are described and compared across drugs based on clinical reports in humans and drug discrimination studies in animals. A third determinant is the behavioral and physiological toxicity that results from acute and chronic use of these drugs. Clinical reports and results of sensitive tests that have been developed for laboratory animals are reviewed. A fourth determinant is the dependence potential that exists with these drugs, measured by tolerance development and the extent to which behavioral and physiological disturbances occur when drug use is terminated.

Antifungal activity of essential oils of Croton species from the Brazilian Caatinga biome.

PubMed

Fontenelle, R O S; Morais, S M; Brito, E H S; Brilhante, R S N; Cordeiro, R A; Nascimento, N R F; Kerntopf, M R; Sidrim, J J C; Rocha, M F G

2008-05-01

To find new antifungal agents among essential oils from Brazilian Croton species. Plant leaves were steam distilled and the obtained essential oils were analyzed by gas chromatography/mass spectroscopy. The main constituents were estragole and anethole for Croton zehntneri, methyl-eugenol and bicyclogermacrene for Croton nepetaefolius and spathulenol and bicyclogermacrene for Croton argyrophylloides. The antifungal activity of essential oils was evaluated against Candida albicans, Candida tropicalis and Microsporum canis by the agar-well diffusion method and the minimum inhibitory concentration (MIC) by the broth microdilution method. Essential oils of Croton species demonstrated better activity against M. canis. Among the three plants C. argyrophylloides showed the best results, with MIC ranging from 9 to 19 microg ml(-1). The acute administration of the essential oil up to 3 g kg(-1) by the oral route to mice was devoid of overt toxicity. The studied essential oils are active in vitro against the dermatophyte M. canis and present relative lack of acute toxicity in vivo. Because of its antifungal activity and low toxicity, the essential oils of studied Croton species are promising sources for new phytotherapeutic agents to treat dermatophytosis.

The relation between molecular structure and biological activity among mononitrophenols containing halogens

USGS Publications Warehouse

Applegate, Vernon C.; Johnson, B.G.H.; Smith, Manning A.

1966-01-01

The results of tests of the biological activity of certain nitrophenols containing halogen are reported. Some of these are shown to be significantly more toxic to larvae of the sea lamprey (Petromyzon marinus L.) than to fishes. It is proposed that the death of lamprey larvae exposed to these compounds results from an acute hypotension (shock) with concomitant circulatory and respiratory failure. Rainbow trout (Salmo gairdneri), on the other hand, appear to die, at higher concentrations of the toxin, due to a chemically-caused mechanical interference with respiration through the gills. A systematic series of studies of mononitrophenols containing halogens disclosed that those phenols having the nitro group in the para-position and a halogen atom or group in the meta-position are generally more toxic to lampreys than to fish. The halogens or halogen groups used in this study were fluorine, chlorine, bromine, and trifluormethyl. The same substituents in other positions only occasionally gave rise to selectively toxic compounds. The relationship between the selectively active class of nitrophenols containing halogens and other related structures is discussed.

Lethal and sub-lethal effects of select macrocyclic lactones insecticides on forager worker honey bees under laboratory experimental conditions.

PubMed

Abdu-Allah, Gamal A M; Pittendrigh, Barry R

2018-01-01

Selective insecticide application is one important strategy for more precisely targeting harmful insects while avoiding or mitigating collateral damage to beneficial insects like honey bees. Recently, macrocyclic lactone-class insecticides have been introduced into the market place as selective bio-insecticides for controlling many arthropod pests, but how to target this selectivity only to harmful insects has yet to be achieved. In this study, the authors investigated the acute toxicity of fourmacrocyclic lactone insecticides (commercialized as abamectin, emamectin benzoate, spinetoram, and spinosad) both topically and through feeding studies with adult forager honey bees. Results indicated emamectin benzoate as topically 133.3, 750.0, and 38.3-fold and orally 3.3, 7.6, and 31.7-fold more toxic, respectively than abamectin, spinetoram and spinosad. Using Hazard Quotients for estimates of field toxicity, abamectin was measured as the safest insecticide both topically and orally for honey bees. Moreover, a significant reduction of sugar solution consumption by treatment group honey bees for orally applied emamectin benzoate and spinetoram suggests that these insecticides may have repellent properties.

Toxicity assessment of common xenobiotic compounds on municipal activated sludge: comparison between respirometry and Microtox.

PubMed

Ricco, Giuseppina; Tomei, M C M Concetta; Ramadori, Roberto; Laera, Giuseppe

2004-04-01

The toxicity of four xenobiotic compounds 3,5-dichlorophenol, formaldehyde, 4-nitrophenol and dichloromethane, representative of industrial wastewater contaminants was evaluated by a simple respirometric procedure set up on the basis of OECD Method 209 and by the Microtox bioassay. Very good reproducibility was observed for both methods, the variation coefficients being in the range of 2-10% for the respirometric procedure and 6-15% for Microtox, values that can be considered very good for a biological method. Comparison of EC(50) data obtained with the two methods shows that in both cases 3,5-dichlorophenol is more toxic than other compounds investigated and dichloromethane has a very low toxicity value. Intermediate EC(50) values were found for the two other chemicals, formaldehyde and 4-nitrophenol. Moreover, the Microtox EC(50) values are generally lower (except for dichloromethane) than the respirometric ones: these differences could be explained by the fact that the Microtox method uses a pure culture of marine species and, therefore, should not necessarily be expected to behave like a community of activated sludge bacteria. In conclusion, both methods can be usefully applied for toxicity detection in wastewater treatment plants but it is advisable to take into account that Microtox is more sensitive than respirometry in estimating the acute toxicity effect on the biomass operating in the plant.

Comprehensive mollusk acute toxicity database improves the use of Interspecies Correlation Estimation (ICE) models to predict toxicity of untested freshwater and endangered mussel species

EPA Science Inventory

Interspecies correlation estimation (ICE) models extrapolate acute toxicity data from surrogate test species to untested taxa. A suite of ICE models developed from a comprehensive database is available on the US Environmental Protection Agency’s web-based application, Web-I...

Acute lead toxicosis via ingestion of spent ammunition in a free-ranging cougar (Puma concolor)

USGS Publications Warehouse

Burco, Julia; Myers, Anne Mary; Schuler, Krysten; Gillin, Colin

2012-01-01

Lead toxicity has long been documented and acknowledged as a significant health issue of water birds and avian scavengers. However, few instances of toxic effects to higher mammalian carnivores have been documented. Here we present an acute case of lead toxicity in a free-ranging cougar (Puma concolor) in Oregon.

Acute lead toxicosis via ingestion of spent ammunition in a free-ranging cougar (Puma concolor).

PubMed

Burco, Julia; Myers, Anne Mary; Schuler, Krysten; Gillin, Colin

2012-01-01

Lead toxicity has long been documented and acknowledged as a significant health issue of water birds and avian scavengers. However, few instances of toxic effects to higher mammalian carnivores have been documented. Here we present an acute case of lead toxicity in a free-ranging cougar (Puma concolor) in Oregon.

Assessing variability in chemical acute toxicity of unionid mussels: Influence of intra- and inter-laboratory testing, life stage, and species - SETAC Abstract

EPA Science Inventory

We developed a toxicity database for unionid mussels to examine the extent of intra- and inter-laboratory variability in acute toxicity tests with mussel larvae (glochidia) and juveniles; the extent of differential sensitivity of the two life stages; and the variation in sensitiv...

Acute methaemoglobinaemia initially treated as organophosphate poisoning leading to atropine toxicity.

PubMed

Kakhandki, Srinivas; Yahya, Mohammed; Praveen, Mudalgi

2012-07-01

A case of unknown compound poisoning is presented. It was initially treated as organophosphate poisoning with lack of response. A timely diagnosis of acute methaemoglobinaemia and iatrogenic atropine toxicity was made based on clinical evaluation. Treatment of methaemoglobinaemia using oral methylene blue and of atropine toxicity with supportive measures could save the patient.

Dosimetric and clinical predictors of radiation-induced lung toxicity in esophageal carcinoma.

PubMed

Zhu, Shu-Chai; Shen, Wen-Bin; Liu, Zhi-Kun; Li, Juan; Su, Jing-Wei; Wang, Yu-Xiang

2011-01-01

Radiation-induced lung toxicity occurs frequently in patients with esophageal carcinoma. This study aims to evaluate the clinical and three-dimensional dosimetric parameters associated with lung toxicity after radiotherapy for esophageal carcinoma. The records of 56 patients treated for esophageal carcinoma were reviewed. The Radiation Therapy Oncology Group criteria for grading of lung toxicity were followed. Spearman's correlation test, the chi-square test and logistic regression analyses were used for statistical analysis. Ten of the 56 patients developed acute toxicity. The toxicity grades were grade 2 in 7 patients and grade 3 in 3 patients; none of the patients developed grade 4 or worse toxicity. One case of toxicity occurred during radiotherapy and 9 occurred 2 weeks to 3 months after radiotherapy. The median time was 2.0 months after radiotherapy. Fourteen patients developed late irradiated lung injury, 3 after 3.5 months, 7 after 9 months, and 4 after 14 months. Radiographic imaging demonstrated patchy consolidation (n = 5), atelectasis with parenchymal distortion (n = 6), and solid consolidation (n = 3). For acute toxicity, the irradiated esophageal volume, number of fields, and most dosimetric parameters were predictive. For late toxicity, chemotherapy combined with radiotherapy and other dosimetric parameters were predictive. No obvious association between the occurrence of acute and late injury was observed. The percent of lung tissue receiving at least 25 Gy (V25), the number of fields, and the irradiated length of the esophagus can be used as predictors of the risk of acute toxicity. Lungs V30, as well as chemotherapy combined with radiotherapy, are predictive of late lung injury.

ORAL TOXICITY OF 1,3-DICHLOROPROPANE: ACUTE, SHORT-TERM, AND LONG-TERM STUDIES IN RATS

EPA Science Inventory

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil...

Methods to assess reproductive effects of environmental chemicals: studies of cadmium and boron administered orally.

PubMed Central

Dixon, R L; Lee, I P; Sherins, R J

1976-01-01

Results of a U.S.S.R.--U.S. cooperative laboratory effort to improve and validate experimental techniques used to assess subtle reproductive effects in male laboratory animals are reported. The present studies attempted to evaluate the reproductive toxicity of cadmium as cadmium chloride and boron as borax (Na2B4O7) and to investigate the mechanism of toxicity in the rat following acute and subchronic oral exposure. In vitro cell separation techniques, in vivo serial mating tests, and plasma assays for hormones were utilized. Effects on the seminal vesicle and prostate were evaluated with chemical and enzyme assays. Clinical chemistry was monitored routinely. Acute oral doses, expressed as boron were 45, 150, and 450 mg/kg while doses for cadmium equivalent were 6.25, 12.5, and 25 mg/kg. Rats were also allowed free access to drinking water containing either boron (0.3, 1.0, and 6.0 mg/l.) or cadmium (0.001, and 0.l mg/l.) for 90 days. Randomly selected animals were studied following 30, 60, and 90 days of treatment. These initial studies, utilizing a variety of methods to assess the reproductive toxicity of environmental substances in male animals, suggest that cadmium and boron at the concentrations and dose regimens tested are without significant reproductive toxicity. PMID:1269508

Acute toxicity of 31 different nanoparticles to zebrafish (Danio rerio) tested in adulthood and in early life stages – comparative study

PubMed Central

Kovrižnych, Jevgenij A.; Zeljenková, Dagmar; Rollerová, Eva; Szabová, Elena; Wimmerová, Soňa

2013-01-01

At present, nanoparticles are beginning to influence our lives in many ways and understanding the environmental health and safety aspect of nanomaterials has become a crucial issue. The aim of the work was to assess and compare the acute toxicity of 31 different nanomaterials to fish mature individuals Danio rerio with that to fish early life stages on using evaluation of the 48- and 96- hour LC50 values. A further aim was to evaluate teratogenicity of the nanoparticles tested to fish eggs. The nanoparticles tested were: 8 pure metals, 10 metal oxides, 5 other metal compounds and their mixtures, 2 silicon compounds, 3 calcium compounds, and 3 carbon compounds. Using 48-h and 96-h tests of acute toxicity (according to OECD 203), we evaluated mortality data, LC50 values, occurrence of malformations, as well as hatching time. In our study, 6 kinds of nanoparticles – calcium oxide, copper, copper in the form of oxide and CuZnFe4O4, magnesium oxide, and nickel – caused cumulative mortality. Two kinds of nanoparticles – copper and silver – were toxic for fish with LC50 values of approximately 3 mg/L. We did not observe marked differences between the 48-hour and 96-hour acute toxicity LC50 values, yet the possibility to evaluate hatching time in the 96-h acute fish toxicity test seems to be an advantage against that of the 48-hour toxicity. PMID:24179431

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.

Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

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

Valdagni, Riccardo; Rancati, Tiziana; Fiorino, Claudio

2008-07-15

Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire.more » Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the first set of nomograms available in the literature specific to symptoms of LGI syndrome and provides clinicians with a tailored probability of the specific outcome. Validation of the tool is in progress.« less

[Acute toxicity effects of three red tide algae on Brachionus plicatilis].

PubMed

Zhou, Wen-Li; Xiao, Hui; Wang, You; Zhai, Hong-Chang; Tang, Xue-Xi

2008-11-01

Acute toxicity testing method was used to study effects of different density of Prorocentrum donghaiense, Heterosigma akashiwo and Alexandrium tamarense on mortality rates and population growth parameter of Brachionus plicatilis under controlled experimental conditions. Results showed that 24 h LC50 values of Prorocentrum donghaiense, Heterosigma akashiwo and Alexandrium tamarense treatment to mortality rate of Brachionus plicatilis were 3.56, 1.21 and 0.49 (x 10(4) cells/mL) respectively. Marked density effects were presented when three species of red tide microalga showed their toxicity to Brachionus plicatilis. There were significant inhibitory effects on Brachionus plicatilis when it was exposed to cells of Prorocentrum donghaiense at the concentration of 10(4) cells/mL, filtrate and cell contents of Heterosigma akashiwo at the concentration of 10(5) cells/mL, and cells, filtrate and cell contents of Alexandrium tamarense at the concentration of 10(3) cells/mL respectively. Inhibitory effects of three species of microalga on Brachionus plicatilis were enhanced with increasing of microalgal density.

Study on the Effect of Heavy metals toxicity according to changing Hardness concentration using D.magna

NASA Astrophysics Data System (ADS)

Chun Sang, H.

2016-12-01

n order to determine and prevent the number of ecological effects of heavy metals in the materials, we have to accurately measure the heavy metals present in the water-based protection ecosystems and may determine the effects to humans. Heavy metals occurred in the industrial effluent which is a state in which the monitor, based on the emission standards are made by the Ministry of Environment and managed and waste water contained Copper, Zinc, lead, etc. These heavy metals are able to express the toxic effects only when present in the free-ions in the aqueous condition, which appears differently affected by the degree to hardness change in accordance with the season, precipitation. Generally changing hardness concentration can not precisely evaluate toxic effects of heavy metals in the water system. Anderson announced a study on bioassay for heavy metals from industrial waste water using Daphnia magna(Anderson, 1944, 1948). Breukelman published study the resitivity difference for the mercury Chloride(HgCl2). Braudouin(1974) compared the zooplankton(Daphnia sp.) acute toxicity of the different heavy metals and confirmed the sensitivity. Shcherban(1979) presented for toxicity evaluation results for the heavy metal of the Daphnia magna according to different temperature conditions. In the United States Environmental Protection Agency(EPA) established a standard test method for water fleas, managed and supervised water ecosystems, and announced the adoption of a bioassay standard method. This study was performed to evaluate acute inhibition using the Daphnia magna for the biological effect of heavy metal ions in water-based toxicity in the hardness change. Evaluation methods were conducted in EPA Water Quality process test criteria. TU(Toxic Unit), NOEC (No Observable Effect Concentration), LOEC (Lowest Observable Effect Concentration), EC50 (Median Effective Concentration) was calculated by Toxcalc 5.0 Program. Keywords : D. magna, Hardness, Toxic Unit, Heavy metal, Industrial effluent Acknowledgement This research was supported by a grant (16IFIP-B089908-03) from Plant Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government. * Corresponding author E-mail address : hcs103@gmail.com(Chun Sang Hong, Ph.D.)

USE OF MODELS TO SUPPORT WATER QUALTIY CRITERIA - A CASE STUDY

EPA Science Inventory

In the United States, current methods for deriving chemical criteria protective of aquatic life depend on acute and chronic toxicity test results involving several species. These results are analyzed statistically to identify chemical concentrations that protect the majority of ...

Non-animal Replacements for Acute Toxicity Testing.

PubMed

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

2015-07-01

Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

Assessing the Toxicity and Bioavailability of 2,4-Dinitroanisole in Acute and Sub-Chronic Exposures Using the Earthworm, Eisenia fetida

DTIC Science & Technology

2010-06-01

different methods, 2nd method chosen for final study: ► Coelomocytes collected in 2 ml Guaiacol Glyceryl Ether ( GGE ) solution, centrifuged, decanted...worm to GGE t= 2mins collect coelomocyte solution 1 row per worm/treatment, obtain measurements through spectrophotometer NRRT analysis 1) 2) BUILDING

Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

PubMed

Strupp, Christian

2011-01-01

The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral toxic properties.

A biosensor for cadmium based on bioconvective patterns

NASA Technical Reports Server (NTRS)

Noever, David A.; Matsos, Helen C.

1990-01-01

An 'in vitro' method for monitoring cadmium, one of the most lethal bivalent heavy metals, can detect biologically active levels. The effects of cadmium tend to concentrate in protozoa far above natural levels and therein begin transferring through freshwater food chains to animals and humans. In a small sample volume (approximately 5 ml) the method uses the toxic response to the protozoa, Tetrahymena pyriformis, to cadmium. The assay relies on macroscopic bioconvective patterns to measure the toxic response, giving a sensitivity better than 1 micro-g/1 and a toxicity threshold to 7 micro-g/1 for Cd(2+). Cadmium hinders pattern formation in a dose-dependent manner. Arrested organism growth arises from slowed division and mutation to non-dividing classes. Unlike previous efforts, this method can be performed in a shallow flow device and does not require electronic or chemical analyses to monitor toxicity.

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

PubMed

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

2017-07-01

Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (p<0.05); and neonates' heart rate decreased 72.7% (p<0.05). In the chronic toxicity test, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute toxicity of gasoline and some additives.

PubMed Central

Reese, E; Kimbrough, R D

1993-01-01

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

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

PubMed Central

2012-01-01

Background SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients. Methods Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeamTM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan. Results All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded. Conclusions Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes. PMID:23216821

Predictors for Rectal and Intestinal Acute Toxicities During Prostate Cancer High-Dose 3D-CRT: Results of a Prospective Multicenter Study

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

Vavassori, Vittorio; Fiorino, Claudio; Rancati, Tiziana

2007-04-01

Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with {>=}70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered. Results: Of 1,132more » patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for particular symptoms.« less

Treatment of relapsed or refractory acute leukemia in childhood with bisantrene combined with high dose aracytine.

PubMed

Leblanc, T; Deméocq, F; Leverger, G; Baruchel, A; Lemerle, S; Vannier, J P; Nelken, B; Guillot, T; Schaison, G

1994-01-01

Bisantrene is an anthracene derivative which has demonstrated activity in acute myeloblastic leukemia (AML) and in lymphoma. The present study was designed to assess the reinduction rate and toxicity of bisantrene (250 mg/m2/d x 5) associated with aracytine (100 mg/m2 twice a day x 5) in refractory and relapsed acute childhood leukemia. Patients who relapsed after bone marrow transplantation were eligible. Twenty-six children were included. Diagnoses were as follows: 13 AML, 9 acute lymphoblastic leukemia (ALL), and 4 undifferentiated leukemia (AUL). All patients had been very highly pretreated, especially with anthracyclines, and most of them were of poor prognosis. The overall response rate was 46% with a 95% confidence interval ranging from 27-65%. According to diagnosis, complete remission (CR) rates are: AML: 5/13, ALL: 5/9, and AUL: 2/4. Four children died, three from infection and one from acute lysis syndrome. The major toxicity was infection with grade 3 and 4 episodes occurring in 42% of patients. No significant cardiac toxicity was noted. Hepatic and renal toxicity was noted. Hepatic and renal toxicity were limited and transient. Bisantrene in association with aracytine is effective in both AML and ALL of childhood. Bisantrene should be evaluated with a five-day schedule in other pediatric malignancies. In children with acute leukemia previously treated with high dose aracytine, new combination regimen is warranted.

Acute and Subacute Toxicity Evaluation of Corn Silk Extract

PubMed Central

Ha, Ae Wha; Kang, Hyeon Jung; Kim, Sun Lim; Kim, Myung Hwan

2018-01-01

Many studies have reported therapeutic efficacy of corn silk extract. However, research on its toxicity and safe dose range is limited. Thus, the objective of this study was to determine the acute and subacute toxicity of corn silk extract in ICR mice. To determine acute toxicity, corn silk extract containing high levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg. Clinical symptoms, mortality, and body weight changes were recorded for 14 days. To determine subacute toxicity, corn silk extract was orally administered to mice over a 4-week period, and then body weight, water and food consumption, and organ weight were determined. In addition, urine and serum analyses were performed. In the acute toxicity study, no death or abnormal symptoms was observed in all treatment groups during the study period. Body weights did not show any significant change compared to those of the control group. Lethal dose of corn silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute toxicity study, there was no corn silk extract related toxic effect on body weight, water intake, food consumption, urine parameters, clinical chemistry, or organ weight. Histopathological examination showed no abnormality related to the administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of corn silk extract containing high levels of maysin was found to be more than 500 mg/kg. PMID:29662850

Acute and Subacute Toxicity Evaluation of Corn Silk Extract.

PubMed

Ha, Ae Wha; Kang, Hyeon Jung; Kim, Sun Lim; Kim, Myung Hwan; Kim, Woo Kyoung

2018-03-01

Many studies have reported therapeutic efficacy of corn silk extract. However, research on its toxicity and safe dose range is limited. Thus, the objective of this study was to determine the acute and subacute toxicity of corn silk extract in ICR mice. To determine acute toxicity, corn silk extract containing high levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg. Clinical symptoms, mortality, and body weight changes were recorded for 14 days. To determine subacute toxicity, corn silk extract was orally administered to mice over a 4-week period, and then body weight, water and food consumption, and organ weight were determined. In addition, urine and serum analyses were performed. In the acute toxicity study, no death or abnormal symptoms was observed in all treatment groups during the study period. Body weights did not show any significant change compared to those of the control group. Lethal dose of corn silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute toxicity study, there was no corn silk extract related toxic effect on body weight, water intake, food consumption, urine parameters, clinical chemistry, or organ weight. Histopathological examination showed no abnormality related to the administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of corn silk extract containing high levels of maysin was found to be more than 500 mg/kg.

Prevention and treatment of Nitrite toxicity in juvenile steelhead trout (Salmo gairdneri)

USGS Publications Warehouse

Wedemeyer, Gary A.; Yasutake, W.T.

1978-01-01

The efficacy of mineral salts, pH, and tetramethylthianine (methylene blue) treatment in reducing the acute toxicity of nitrite to fingerling steelhead trout (Salmo gairdneri) was determined using a static bioassay system at 10 °C. The acute toxicity (96-h LC50) was reduced by a factor of about 24 for 5-g steelhead and 13 for 10-g fish when the total water hardness was increased from 25 to 300 mg/L (as CaCO3). NaCl or CaCl2 additions (0–200 mg/L) reduced toxicity by a factor of up to 3 for NaCl and 50 for CaCl2. Increasing the pH from 6.0 to 8.0 decreased toxicity by a factor of about 8 for the smaller and 3 for the larger fish. Methylene blue at 0.1 or 1.0 mg/L was effective in decreasing acute toxicity. For alleviating methemoglobinemia, removing the fish to freshwater for 48 h was about as effective as 1.0 mg/L methylene blue. Chronic exposure in soft water to 0.03 mg/L NO2-N for 6 mo caused no significant growth reduction, gill histological changes, hematological dyscrasias, or impaired ability of the smolts to adapt to 30‰ seawater and grow for an additional 2 mo. Key words: nitrite, toxicity, fish, methylene blue, pH, salts, acute toxicity, chronic toxicity

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

PubMed

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

2015-01-01

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

Catatonia from its creation to DSM-V: Considerations for ICD.

PubMed

Fink, Max

2011-07-01

Catatonia was delineated only as a type of schizophrenia in the many American Psychiatric Association DSM classifications and revisions from 1952 until 1994 when "catatonia secondary to a medical condition" was added. Since the 1970s the diagnosis of catatonia has been clarified as a syndrome of rigidity, posturing, mutism, negativism, and other motor signs of acute onset. It is found in about 10% of psychiatric hospital admissions, in patients with depressed and manic mood states and in toxic states. It is quickly treatable to remission by benzodiazepines and by ECT. The DSM-V revision proposes catatonia in two major diagnostic classes, specifiers for 10 principal diagnoses, and deletion of the designation of schizophrenia, catatonic type. This complex recommendation serves no clinical or research purpose and confuses treatment options. Catatonia is best considered in the proposed ICD revision as a unique syndrome of multiple forms warranting a single unique defined class similar to that of delirium.

The acute toxicity of the metaldehyde on the climbing perch

NASA Astrophysics Data System (ADS)

Wahida Mohamad Ismail, Syamimi; Aini Dahalan, Farrah; Zakaria, Ammar; Mad Shakaff, Ali Yeon; Aqlima Ahmad, Siti; Shukor, Mohd Yunus Abd; Khalizan Sabullah, Mohd; Khalil, Khalilah Abdul; Jalil, Mohd Faizal Ab

2018-03-01

In Asia, Climbing perch (Anabas testudineus) is commonly found in paddy fields and irrigation systems. Due to its habitat, Climbing perch is exposed to toxic pesticides used in paddy fields such as metaldehyde which is one of the most widely used molluscicide. This study aims to determine the acute toxicity Lethal Concentration50 (LC50) of metaldehyde and its effect on the behaviour and physical changes of the Climbing perch. The fish mortality responses to six different metaldehyde concentrations ranging from 180 to 330 mg/L were investigated. The 96-h LC50 values were determined and analysed using three different analysis methods which is arithmetic, logarithmic and probit graphic. The LC50 values obtained in this study were 239, 234 and 232 mg/L, respectively. After 96-h of exposure to metaldehyde, the fish showed a series of abnormal behavioural response in all cases: imbalance position, and restlessness of movement. The LC50 values show that metaldehyde is moderately toxic to the Climbing perch indicating that metaldehyde is not destructive to Climbing perch. However, long term exposure of aquatic organisms to the metaldehyde means a continuous health risk for the fish population as they are more vulnerable and it is on high risk for human to consume this toxicated fishes.

Assessing Aromatic-Hydrocarbon Toxicity to Fish Early Life Stages Using Passive-Dosing Methods and Target-Lipid and Chemical-Activity Models.

PubMed

Butler, Josh D; Parkerton, Thomas F; Redman, Aaron D; Letinski, Daniel J; Cooper, Keith R

2016-08-02

Aromatic hydrocarbons (AH) are known to impair fish early life stages (ELS). However, poorly defined exposures often confound ELS-test interpretation. Passive dosing (PD) overcomes these challenges by delivering consistent, controlled exposures. The objectives of this study were to apply PD to obtain 5 d acute embryo lethality and developmental data and 30 d chronic embryo-larval survival and growth-effects data using zebrafish with different AHs; to analyze study and literature toxicity data using target-lipid (TLM) and chemical-activity (CA) models; and to extend PD to a mixture and test the assumption of AH additivity. PD maintained targeted exposures over a concentration range of 6 orders of magnitude. AH toxicity increased with log Kow up to pyrene (5.2). Pericardial edema was the most sensitive sublethal effect that often preceded embryo mortality, although some AHs did not produce developmental effects at concentrations causing mortality. Cumulative embryo-larval mortality was more sensitive than larval growth, with acute-to-chronic ratios of <10. More-hydrophobic AHs did not exhibit toxicity at aqueous saturation. The relationship and utility of the TLM-CA models for characterizing fish ELS toxicity is discussed. Application of these models indicated that concentration addition provided a conservative basis for predicting ELS effects for the mixture investigated.

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

EPA Science Inventory

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

Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

DTIC Science & Technology

2016-07-01

Particles (VLPs). The rationale is based on the beneficial effect of SV40 VLPs on an Acute Kidney Injury (AKI) model in mice, previously demonstrated...signaling which, as was demonstrated, protect mice kidneys from apoptosis, necrosis and consequent damage induced by a toxic (mercury) insult, increasing...recombinant VP1, without any genetic material. Using a mouse model for toxic Acute Kidney Injury (AKI), we demonstrated that systemic

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

Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

PubMed

Maynard, Samuel K; Edwards, Peter; Wheeler, James R

2014-07-01

Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single-stage designs. © 2014 The Authors.

40 CFR 158.2060 - Biochemical pesticides nontarget organisms and environmental fate data requirements table.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., one avian dietary, one acute freshwater fish, one acute freshwater invertebrate study, plant toxicity... R R CR R CR TGAI, EP 2, 3, 4, 5 850.1010 Aquatic invertebrate acute toxicity, freshwater R R CR R CR....1500 Freshwater fish/invertebrate testing CR CR NR CR NR TGAI 10 850.1025850.1035 850.1045 850.1055 850...

Toxic effects of selenium and copper on the planarian, Dugesia dorotocephala

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

Rauscher, J.D.

1988-01-01

Aquatic toxicologists have become increasingly concerned with the effects of sublethal concentrations of toxicants on aquatic organisms. Sublethal effects of toxicants on freshwater invertebrates were reviewed. Selenium (Se) and copper (Cu) are both essential trace elements and toxicants. Se has been reported to alter the toxicity of heavy metals. Planarians, Dugesia dorotocephala, were used as test animals. The objectives of this study were to determine: (1) acute toxicity of Se on planarians and the effect of the number of planarians per test chamber, (2) interaction of the acute toxicity of Se and Cu on planarians, and (3) sublethal effects ofmore » Se and Cu on planarians.« less

Acute radiotherapy toxicity in 57 dogs with gross and microscopic mast cell tumours.

PubMed

Blackwood, L; Tanis, J B; Harper, A; Amores-Fuster, I; Killick, D R; Finotello, R

2018-05-15

Mast cell tumours (MCTs) are commonly treated with radiation therapy, most often in a microscopic disease setting. Poorer outcomes are expected in patients with gross disease, and irradiation of gross disease may be associated with greater toxicity. The aim of this study was to compare acute radiation adverse events (AE) in dogs with gross and microscopic MCTs receiving radiotherapy. Fifty-seven dogs were included, 28 with gross disease and 29 with microscopic. In order to assess mucosal and skin toxicity, patients were assigned to 2 groups: head (29 patients, 14 patients with gross and 15 microscopic) and other sites (28 patients, 14 each). All were treated with external beam radiotherapy, and toxicity assessed at the end of treatment and 10 to 14 days later (first recheck). All patients developed some acute radiation toxicity by the end of the course. However, there was no difference in the severity of toxicity between gross and microscopic disease in either site group at either time point. The only variable associated with an increased frequency of grade 2 or 3 toxicity at the first recheck was the use of prednisolone prior to radiotherapy (P = .05). No other factors were identified which were associated with increased toxicity. For the head group, the site of highest grade toxicity was mucosa or, if included in the field, nasal planum, which was often more severely affected than the mucosa. No significant late toxicity was identified. Two dogs developed acute haematemesis during the radiotherapy course, but both completed the course without further events. © 2018 John Wiley & Sons Ltd.

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

USGS Publications Warehouse

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

2007-01-01

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

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

USGS Publications Warehouse

Besser, J.M.; Mebane, C.A.; Mount, D.R.; Ivey, C.D.; Kunz, J.L.; Greer, I.E.; May, T.W.; Ingersoll, C.G.

2007-01-01

Studies of fish communities of streams draining mining areas suggest that sculpins (Cottus spp.) may be more sensitive than salmonids to adverse effects of metals. We compared the toxicity of zinc, copper, and cadmium to mottled sculpin (C. bairdi) and rainbow trout (Onchorhynchus mykiss) in laboratory toxicity tests. Acute (96-h) and early life-stage chronic (21- or 28-d) toxicity tests were conducted with rainbow trout and with mottled sculpins from populations in Minnesota and Missouri, USA, in diluted well water (hardness = 100 mg/L as CaCO3). Acute and chronic toxicity of metals to newly hatched and swim-up stages of mottled sculpins differed between the two source populations. Differences between populations were greatest for copper, with chronic toxicity values (ChV = geometric mean of lowest-observed-effect concentration and no-observed-effect concentration) of 4.4 ??g/L for Missouri sculpins and 37 ??g/L for Minnesota sculpins. Cadmium toxicity followed a similar trend, but differences between sculpin populations were less marked, with ChVs of 1.1 ??g/L (Missouri) and 1.9 ??g/L (Minnesota). Conversely, zinc was more toxic to Minnesota sculpins (ChV = 75 ??g/L) than Missouri sculpins (chronic ChV = 219 ??g/L). Species-average acute and chronic toxicity values for mottled sculpins were similar to or lower than those for rainbow trout and indicated that mottled sculpins were among the most sensitive aquatic species to toxicity of all three metals. Our results indicate that current acute and chronic water quality criteria for cadmium, copper, and zinc adequately protect rainbow trout but may not adequately protect some populations of mottled sculpins. Proposed water quality criteria for copper based on the biotic ligand model would be protective of both sculpin populations tested. ?? 2007 SETAC.

PRN 2001-2: Acute Toxicity Data Requirements For Granular Pesticide Products, Including Those With Granular Fertilizers in the Product.

EPA Pesticide Factsheets

This PR Notice announces guidance intended to streamline the acute toxicity review and classification process for certain granular pesticide products, including those products that contain granular fertilizers.

USER GUIDE: ACUTE TO CHRONIC ESTIMATION

EPA Science Inventory

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

ACUTE BEHAVIORAL TOXICITY OF SULFOLANE: INFLUENCE OF HYPOTHERMIA

EPA Science Inventory

Sulfolane is a solvent which produces hypothermia and decreased oxygen consumption following acute exposure. In the present experiment, the author investigated effects of sulfolane on a behavioral measure of toxicity at ambient temperatures which would either prevent or facilitat...

Toxic Hazards Research Unit

NASA Technical Reports Server (NTRS)

Macewen, J. D.; Vernot, E. H.

1971-01-01

The activities of the Toxic Hazards Research Unit (THRU) for the period of June 1970 through May 1971 reviewed. Modification of the animal exposure facilities primarily for improved human safety but also for experimental integrity and continuity are discussed. Acute toxicity experiments were conducted on hydrogen fluoride (HF), hydrogen chloride (HCl), nitrogen dioxide (NO2), and hydrogen cyanide (HCN) both singly and in combination with carbon dioxide (CO). Additional acute toxicity experiments were conducted on oxygen difluoride (OF2) and chlorine pentafluoride (ClF5). Subacute toxicity studies were conducted on methylisobutylketone and dichloromethane (methylene dichloride). The interim results of further chronic toxicity experiments on monomethylhydrazine (MMH) are also described.

Acute and subchronic oral toxicity of Coriolus versicolor standardized water extract in Sprague-Dawley rats.

PubMed

Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Lim, Chung Pin; Asmawi, Mohd Zaini; Yam, Mun Fei

2011-10-11

Coriolus versicolor, which is known as Yun Zhi, is one of the commonly used Chinese medicinal herbs. Recent studies have demonstrated its antitumor activities on cancer cells which led to its widespread use in cancer patient. However, little toxicological information is available regarding its safety. The present study evaluated the potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats. In acute toxicity study, Coriolus versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6 males, 6 females) at single doses of varying concentrations 1250, 2500 and 5000 mg/kg. In subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28 days to male and female SD rats respectively. General behavior, adverse effects and mortality were determined throughout the experimental period. Haematological and biochemical parameters, relative organ weights and histopathological were evaluated at the end of the experiment. There were no mortality and signs of toxicity in acute and subchronic toxicity studies. In the single dose acute toxicity and repeated dose 28-day subchronic toxicity studies, there were no significant difference in body weight, relative organ weight, haematological parameters, clinical chemistry, gross pathology and histopathology between treatment and control groups. Coriolus versicolor water extract did not cause remarkable adverse effect in SD rats. The oral lethal dose of Coriolus versicolor water extract is more than 5000 mg/kg and no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is 5000 mg/kg per day for 28 days. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Combining polar organic chemical integrative samplers (POCIS) with toxicity testing to evaluate pesticide mixture effects on natural phototrophic biofilms.

PubMed

Pesce, Stéphane; Morin, Soizic; Lissalde, Sophie; Montuelle, Bernard; Mazzella, Nicolas

2011-03-01

Polar organic chemical integrative samplers (POCIS) are valuable tools in passive sampling methods for monitoring polar organic pesticides in freshwaters. Pesticides extracted from the environment using such methods can be used to toxicity tests. This study evaluated the acute effects of POCIS extracts on natural phototrophic biofilm communities. Our results demonstrate an effect of POCIS pesticide mixtures on chlorophyll a fluorescence, photosynthetic efficiency and community structure. Nevertheless, the range of biofilm responses differs according to origin of the biofilms tested, revealing spatial variations in the sensitivity of natural communities in the studied stream. Combining passive sampler extracts with community-level toxicity tests offers promising perspectives for ecological risk assessment. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study.

PubMed

Swords, Ronan T; Erba, Harry P; DeAngelo, Daniel J; Bixby, Dale L; Altman, Jessica K; Maris, Michael; Hua, Zhaowei; Blakemore, Stephen J; Faessel, Hélène; Sedarati, Farhad; Dezube, Bruce J; Giles, Francis J; Medeiros, Bruno C

2015-05-01

This trial was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8-activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60-min intravenous infusion on days 1, 3 and 5 (schedule A, n = 27), or days 1, 4, 8 and 11 (schedule B, n = 26) every 21-days. Dose escalation proceeded using a standard '3 + 3' design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83 mg/m(2) , respectively. On schedule A, hepatotoxicity was dose limiting. Multi-organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target-specific activity of pevonedistat. In conclusion, administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. © 2015 John Wiley & Sons Ltd.

Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection

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

Munro, N.B.; Ambrose, K.R.; Watson, A.P.

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is not evidence that itmore » causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxicity, the nerve agent exposure is the extraordinarily high acute toxicity of these substances. Futhermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent release, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. 187 refs., 3 figs., 7 tabs.« less

Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

PubMed Central

Munro, N

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Images Figure 2. PMID:9719666

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Anal Cancer

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

Hodges, Joseph C., E-mail: joseph.hodges@utsouthwestern.edu; Beg, Muhammad S.; Das, Prajnan

2014-07-15

Purpose: To compare the cost-effectiveness of intensity modulated radiation therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal cancer and determine disease, patient, and treatment parameters that influence the result. Methods and Materials: A Markov decision model was designed with the various disease states for the base case of a 65-year-old patient with anal cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health states accounting for rates of local failure, colostomy failure, treatment breaks, patient prognosis, acute and late toxicities, and the utility of toxicities were informed by existing literature and analyzed with deterministic and probabilistic sensitivitymore » analysis. Results: In the base case, mean costs and quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291 (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost-effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per QALY, respectively. Conclusions: In our base model, IMRT was a cost-ineffective strategy despite the reduced acute treatment toxicities and their associated costs of management. The model outcome was sensitive to variations in local and colostomy failure rates, as well as patient-reported utilities relating to acute toxicities.« less

Neurotoxicity in Aquatic Systems: Evaluation of Anthropogenic Trace Substances

EPA Science Inventory

The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize large numbers of chemicals for developmental toxicity, as well as acute and developmental neurotoxicity. In this endeavor, one of our focuses is on contaminants found in drinking water. To exp...

Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans

PubMed Central

Cezairliyan, Brent; Vinayavekhin, Nawaporn; Grenfell-Lee, Daniel; Yuen, Grace J.; Saghatelian, Alan; Ausubel, Frederick M.

2013-01-01

Pathogenic microbes employ a variety of methods to overcome host defenses, including the production and dispersal of molecules that are toxic to their hosts. Pseudomonas aeruginosa, a Gram-negative bacterium, is a pathogen of a diverse variety of hosts including mammals and the nematode Caenorhabditis elegans. In this study, we identify three small molecules in the phenazine class that are produced by P. aeruginosa strain PA14 that are toxic to C. elegans. We demonstrate that 1-hydroxyphenazine, phenazine-1-carboxylic acid, and pyocyanin are capable of killing nematodes in a matter of hours. 1-hydroxyphenazine is toxic over a wide pH range, whereas the toxicities of phenazine-1-carboxylic acid and pyocyanin are pH-dependent at non-overlapping pH ranges. We found that acidification of the growth medium by PA14 activates the toxicity of phenazine-1-carboxylic acid, which is the primary toxic agent towards C. elegans in our assay. Pyocyanin is not toxic under acidic conditions and 1-hydroxyphenazine is produced at concentrations too low to kill C. elegans. These results suggest a role for phenazine-1-carboxylic acid in mammalian pathogenesis because PA14 mutants deficient in phenazine production have been shown to be defective in pathogenesis in mice. More generally, these data demonstrate how diversity within a class of metabolites could affect bacterial toxicity in different environmental niches. PMID:23300454

Acute Oral Toxicity of Trimethylolethane Trinitrate (TMETN) in Sprague- Dawley Rats

DTIC Science & Technology

1989-07-01

classification scheme of Hodge and Steiner, these results indicate that TMETN is a slightly toxic compound.1 20. ON-RIBUTION /AVAILABILITY OF ABSTRACT 21. ABSTRACT...the classification scheme of Hodge and Sterner, these results indcate that TMETN is a slightly toxic compound. KEY WORDS: Acute Oral Toxicit-y...Dawley rats and 1027.4 63.7 mg/kg in female Sprague-Dawley rats. These MLD values place TMETN in the "slightly toxic" range by the system of Hodge and

Application of biomonitoring and support vector machine in water quality assessment*

PubMed Central

Liao, Yue; Xu, Jian-yu; Wang, Zhu-wei

2012-01-01

The behavior of schools of zebrafish (Danio rerio) was studied in acute toxicity environments. Behavioral features were extracted and a method for water quality assessment using support vector machine (SVM) was developed. The behavioral parameters of fish were recorded and analyzed during one hour in an environment of a 24-h half-lethal concentration (LC50) of a pollutant. The data were used to develop a method to evaluate water quality, so as to give an early indication of toxicity. Four kinds of metal ions (Cu2+, Hg2+, Cr6+, and Cd2+) were used for toxicity testing. To enhance the efficiency and accuracy of assessment, a method combining SVM and a genetic algorithm (GA) was used. The results showed that the average prediction accuracy of the method was over 80% and the time cost was acceptable. The method gave satisfactory results for a variety of metal pollutants, demonstrating that this is an effective approach to the classification of water quality. PMID:22467374

A critical review of the application of polymer of low concern and regulatory criteria to fluoropolymers.

PubMed

Henry, Barbara J; Carlin, Joseph P; Hammerschmidt, Jon A; Buck, Robert C; Buxton, L William; Fiedler, Heidelore; Seed, Jennifer; Hernandez, Oscar

2018-05-01

Per- and polyfluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative, and biological stability. They have negligible residual monomer and oligomer content and low to no leachables. Fluoropolymers are practically insoluble in water and not subject to long-range transport. With a molecular weight well over 100 000 Da, fluoropolymers cannot cross the cell membrane. Fluoropolymers are not bioavailable or bioaccumulative, as evidenced by toxicology studies on polytetrafluoroethylene (PTFE): acute and subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation, and thrombogenicity. Clinical studies of patients receiving permanently implanted PTFE cardiovascular medical devices demonstrate no chronic toxicity or carcinogenicity and no reproductive, developmental, or endocrine toxicity. This paper brings together fluoropolymer toxicity data, human clinical data, and physical, chemical, thermal, and biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "polymers of low concern" (PLC). This review concludes that fluoropolymers are distinctly different from other polymeric and nonpolymeric PFAS and should be separated from them for hazard assessment or regulatory purposes. Grouping fluoropolymers with all classes of PFAS for "read across" or structure-activity relationship assessment is not scientifically appropriate. Integr Environ Assess Manag 2018;14:316-334. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

PubMed Central

Wang, Wen; Jin, Minghua; Du, Zhongjun; Li, Yanbo; Duan, Junchao; Yu, Yongbo; Sun, Zhiwei

2013-01-01

This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process. PMID:23593469

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

Treatment-Related Toxicities in Older Adults with Head and Neck Cancer: A Population-Based Analysis

PubMed Central

O’Neill, Caitriona B.; Baxi, Shrujal S.; Atoria, Coral L.; O’Neill, James P.; Henman, Martin C.; Sherman, Eric J.; Lee, Nancy Y.; Pfister, David G.; Elkin, Elena B.

2016-01-01

Background Despite advantages in terms of cancer control and organ preservation, the benefits of chemoradiation (CTRT) may be offset by potentially severe, treatment-related toxicities particularly in older patients. Our objectives were to assess the type and frequency of toxicities in older adults with locally or regionally advanced, head and neck squamous cell carcinoma of the (HNSCC) receiving either primary CTRT or RT alone. Methods Using SEER cancer registry data linked with Medicare claims, we identified patients aged 66 years or older with locally advanced HNSCC, diagnosed 2001–2009, who received CTRT or RT alone. We examined differences in the frequency of toxicity-related hospital admissions and emergency room (ER) visits as well as feeding tube use and estimated the impact of chemotherapy on the likelihood of toxicity, controlling for demographic and disease characteristics. Results Of patients who received CTRT (N=1,502), 62% had a treatment-related toxicity, compared with 46% of patients who received RT alone (N=775). Controlling for demographic and disease characteristics, CTRT patients were twice as likely to experience an acute toxicity compared with their RT only peers. Fifty-five percent of CTRT patients had a feeding tube placed during or after treatment compared with 28% of the RT-only group. Conclusions In this population-based cohort of older adults with HNSCC, the rate of acute toxicities and feeding tube use in patients receiving CTRT was considerable. It is possible that for certain older patients, the potential benefit of adding CT to RT does not outweigh the harms of this combined modality therapy. PMID:25728057

Phytochemical screening and toxicity studies on the methanol extract of the seeds of moringa oleifera.

PubMed

Ajibade, Temitayo Olabisi; Arowolo, Ruben; Olayemi, Funsho Olakitike

2013-05-07

The seeds of Moringa oleifera were collected, air-dried, pulverized, and subjected to cold extraction with methanol. The methanol extract was screened phytochemically for its chemical components and used for acute and sub-acute toxicity studies in rats. The phytochemical screening revealed the presence of saponins, tannins, terpenes, alkaloids, flavonoids, carbohydrates, and cardiac glycosides but the absence of anthraquinones. Although signs of acute toxicity were observed at a dose of 4,000 mg kg-1 in the acute toxicity test, and mortality was recorded at 5,000 mg kg-1, no adverse effect was observed at concentrations lower than 3,000 mg kg-1. The median lethal dose of the extract in rat was 3,873 mg kg-1. Sub-acute administration of the seed extract caused significant (p<0.05) increase in the levels of alanine and aspartate transferases (ALT and AST), and significant (p<0.05) decrease in weight of experimental rats, at 1,600 mg kg-1. The study concludes that the extract of seeds of M. oleifera is safe both for medicinal and nutritional uses.

Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

PubMed

Hamilton, Daniel George; Bale, Rebecca; Jones, Claire; Fitzgerald, Emma; Khor, Richard; Knight, Kellie; Wasiak, Jason

2016-06-01

The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using poisons information service data to assess the acute harms associated with novel psychoactive substances.

PubMed

Wood, D M; Hill, S L; Thomas, S H L; Dargan, P I

2014-01-01

Novel psychoactive substances (NPS) can cause significant acute toxicity but usually little is known about their toxicity when they enter the recreational drug scene. Current data sources include online user forums, user questionnaires, case reports/series, and deaths; however, these are limited by their focus on sub-populations and generally include severe cases and specific geographical areas. Approximately 54% of countries have at least one poisons information service (in 2012 there were 274 worldwide) providing advice to healthcare professionals and/or the public on poisoning. They provide advice on recreational drug and NPS toxicity. In 2012, 2.5% of telephone enquiries to the UK National Poisons Information Service and 2.4% of enquiries to US poisons centres related to recreational drugs. Data are collected at population level and can be used to complement other data sources with clinical details on acute NPS toxicity and geographical/time patterns of toxicity. Like other acute NPS toxicity data, poisons centre data should be interpreted within their limitations, notably the absence of analytical confirmation and reliance on secondary reporting of clinical features. This manuscript demonstrates the breadth and depth of poisons information service data in the literature with a focus on mephedrone and synthetic cannabinoid-receptor agonists. In our opinion it would be possible to develop a more robust and systematic reporting system using a network of poisons information services both within and across countries that would be complimentary to other datasets on acute NPS toxicity and allow more accurate data triangulation. Copyright © 2014 John Wiley & Sons, Ltd.

Clinical and neuropathological findings of acute carbon monoxide toxicity in chihuahuas following smoke inhalation.

PubMed

Kent, Marc; Creevy, Kate E; Delahunta, Alexander

2010-01-01

Three adult Chihuahuas were presented for evaluation after smoke inhalation during a house fire. All three dogs received supportive care and supplemental oxygen. After initial improvement, the dogs developed seizures. Despite anticonvulsant therapy and supportive care, the dogs died. The brains of two dogs were examined. Lesions were identified that were compatible with acute carbon monoxide (CO) toxicity. Lesions were confined to the caudate nucleus, the globus pallidus, and the substantia nigra bilaterally, as well as the cerebellum, cerebral cortex, and dorsal thalamus. This case report describes the clinicopathological sequelae in acute CO toxicity.

Comparative acute toxicity of shale and petroleum derived distillates.

PubMed

Clark, C R; Ferguson, P W; Katchen, M A; Dennis, M W; Craig, D K

1989-12-01

In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and "residual" distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (greater than 5 g/kg LD50) and dermal (greater than 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (greater than 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (greater than 4.8 mg/L) and raw shale oil (greater than 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

PubMed

Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

2013-06-01

In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

Structural and functional properties of antibodies to the superantigen TSST-1 and their relationship to menstrual toxic shock syndrome.

PubMed

Kansal, Rita; Davis, Catherine; Hansmann, Melanie; Seymour, Jon; Parsonnet, Jeffrey; Modern, Paul; Gilbert, Steve; Kotb, Malak

2007-05-01

Menstrual toxic shock syndrome (mTSS) is an acute febrile disease accompanied by hypotension and multiple organ involvement. Infection with Staphylococcus aureus producing the superantigen toxic shock syndrome toxin-1 (TSST-1) vaginally is necessary; however, only a small fraction of those infected with TSST-1 producing bacteria actually develop mTSS, suggesting that host factors modulate disease susceptibility. Serum antibodies to the toxin protect against development of the syndrome, but not all antibodies can neutralize the toxin. We set out to determine whether risk of developing the syndrome is related to the absence of neutralizing antibody and if antibody isotypes influence the neutralization capacity. In healthy subjects, TSST-1-binding serum antibodies were exclusively of the IgG and IgM classes; however, toxin-neutralizing capacity was correlated to the TSST-1-specific IgG1 and IgG4 antibodies (r (2)=0.88, p<0.0001 and 0.33, p<0.0086, respectively) but not with IgM antibodies. Specific IgA was not detectable. Compared to healthy matched controls who were colonized vaginally with S. aureus, IgG1 anti-TSST-1 antibodies and toxin neutralizing activity was lacking in all of the acute phases and in the majority of convalescent sera, suggesting that these patients may be incapable of generating TSST-1 neutralizing antibodies. These new findings support the hypothesis that host factors are important in the development of mTSS and that the anti-toxin isotype impacts antibody functionality.

Functional Consequences of Repeated Organophosphate Exposure: Potential Non-Cholinergic Mechanisms

PubMed Central

Terry, A.V.

2012-01-01

The class of chemicals known as the “organophosphates” (OPs) comprises many of the most common agricultural and commercial pesticides that are used worldwide as well as the highly toxic chemical warfare agents. The mechanism of the acute toxicity of OPs in both target and non-target organisms is primarily attributed to inhibitory actions on various forms of cholinesterase leading to excessive peripheral and central cholinergic activity. However, there is now substantial evidence that this canonical (cholinesterase-based) mechanism cannot alone account for the wide-variety of adverse consequences of OP exposure that have been described, especially those associated with repeated exposures to levels that produce no overt signs of acute toxicity. This type of exposure has been associated with prolonged impairments in attention, memory, and other domains of cognition, as well as chronic illnesses where these symptoms are manifested (e.g., Gulf War Illness, Alzheimer’s disease). Due to their highly reactive nature, it is not surprising that OPs might alter the function of a number of enzymes and proteins (in addition to cholinesterase). However, the wide variety of long-term neuropsychiatric symptoms that have been associated with OPs suggests that some basic or fundamental neuronal process was adversely affected during the exposure period. The purpose of this review is to discuss several non-cholinesterase targets of OPs that might affect such fundamental processes and includes cytoskeletal and motor proteins involved in axonal transport, neurotrophins and their receptors, and mitochondria (especially their morphology and movement in axons). Potential therapeutic implications of these OP interactions are also discussed. PMID:22465060

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.

REDUCING UNCERTAINTY IN AIR TOXICS RISK ASSESSMENT: A MECHANISTIC EXPOSURE-DOSE-RESPONSE (EDR) MODEL FOR ASSESSING THE ACUTE NEUROTOXICITY OF VOLATILE ORGANIC COMPOUNDS (VOCS) BASED UPON A RECEPTOR-MEDIATED MODE OF ACTION

EPA Science Inventory

SUMMARY: The major accomplishment of NTD’s air toxics program is the development of an exposure-dose- response model for acute exposure to volatile organic compounds (VOCs), based on momentary brain concentration as the dose metric associated with acute neurological impairments...

Acute toxicity of live and decomposing green alga Ulva ( Enteromorpha) prolifera to abalone Haliotis discus hannai

NASA Astrophysics Data System (ADS)

Wang, Chao; Yu, Rencheng; Zhou, Mingjiang

2011-05-01

From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides") occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva ( Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

Acute Toxicity of Ammonia, Nitrite and Nitrate to Shrimp Litopenaeus vannamei Postlarvae in Low-Salinity Water.

PubMed

Valencia-Castañeda, Gladys; Frías-Espericueta, Martin G; Vanegas-Pérez, Ruth C; Pérez-Ramírez, Jesús A; Chávez-Sánchez, María C; Páez-Osuna, Federico

2018-05-12

Shrimp farming in low salinities waters is an alternative to increasing production, and counteracting disease problems in brackish and marine waters. However, in low-salinity waters, toxicity of nitrogen compounds increases, and there is no available data of its acute toxicity in shrimp postlarvae. This study determined the acute toxicity of ammonia, nitrite and nitrate in Litopenaeus vannamei postlarvae in 1 and 3 g/L salinity, as well as the safety levels. The LC 50 confirms that nitrite is more toxic than ammonia and nitrate in low salinity waters, and that its toxicity increases with a decrease in salinity. The safe levels estimated for salinities of 1 and 3 g/L were 0.54 and 0.81 mg/L for total ammonia-N, 0.17 and 0.25 mg/L for NO 2 -N, and 5.6 and 21.5 mg/L for NO 3 -N, respectively.

Ecological risk assessment of bisphenol A in surface waters of China based on both traditional and reproductive endpoints.

PubMed

Guo, Lei; Li, Zhengyan; Gao, Pei; Hu, Hong; Gibson, Mark

2015-11-01

Bisphenol A (BPA) occurs widely in natural waters with both traditional and reproductive toxicity to various aquatic species. The water quality criteria (WQC), however, have not been established in China, which hinders the ecological risk assessment for the pollutant. This study therefore aims to derive the water quality criteria for BPA based on both acute and chronic toxicity endpoints and to assess the ecological risk in surface waters of China. A total of 15 acute toxicity values tested with aquatic species resident in China were found in published literature, which were simulated with the species sensitivity distribution (SSD) model for the derivation of criterion maximum concentration (CMC). 18 chronic toxicity values with traditional endpoints were simulated for the derivation of traditional criterion continuous concentration (CCC) and 12 chronic toxicity values with reproductive endpoints were for reproductive CCC. Based on the derived WQC, the ecological risk of BPA in surface waters of China was assessed with risk quotient (RQ) method. The results showed that the CMC, traditional CCC and reproductive CCC were 1518μgL(-1), 2.19μgL(-1) and 0.86μgL(-1), respectively. The acute risk of BPA was negligible with RQ values much lower than 0.1. The chronic risk was however much higher with RQ values of between 0.01-3.76 and 0.03-9.57 based on traditional and reproductive CCC, respectively. The chronic RQ values on reproductive endpoints were about threefold as high as those on traditional endpoints, indicating that ecological risk assessment based on traditional effects may not guarantee the safety of aquatic biota. Copyright © 2015 Elsevier Ltd. All rights reserved.

Combined modality therapy for HIV-infected patients with squamous cell carcinoma of the anus: Outcomes and toxicities

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

Edelman, Scott; Johnstone, Peter

Purpose: We report toxicity and survival data of human immunodeficiency virus (HIV)-infected men with anal carcinoma treated with combined modality therapy (CMT) of radiotherapy and concurrent chemotherapy. Methods and Materials: A retrospective review was performed on the records of 17 HIV-positive patients with anal squamous cell carcinoma treated with CMT at our institution between 1991 and 2004. Radiotherapy consisted of 30.6 to 45 Gy to the pelvis, total dose of 50.4 to 59.4 Gy to initial gross disease, at 1.8 Gy/fraction. Chemotherapy consisted of 5-fluorouracil and either mitomycin C or cisplatin. The mean follow-up was 25.6 months (median, 15.6 months;more » range, 4.6-106 months). Results: Significant acute skin and hematologic toxicity developed in 8 of 17 and 9 of 17 patients, respectively. One patient died 12 days after treatment of progressive disease and sepsis. Significant late toxic sequelae developed in 3 patients: 1 anorectal ulcer, 2 dermatologic (perianal ulceration, hemorrhagic perineal sores and suspected fissure). Fourteen of 15 patients with Stage I-III disease had a complete response; 2 complete responders subsequently had a relapse in the anorectum. For all patients, actuarial 18-month survival was 67%. For patients with Stage I-III disease, survival at last follow-up by low CD4 count (<200) vs. high count (>200) was 4 of 7 vs. 7 of 8, respectively; significant acute toxicities developed in 4 of 8 vs. 6 of 9, respectively. Conclusion: For HIV patients with anal carcinoma, CMT yields reasonable local control with significant acute complications. Survival is lower than in the general population, attributable more to the underlying infection than to the malignancy.« less

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

Theberge, Valerie, E-mail: valerie.theberge.1@ulaval.c; Harel, Francois; Dagnault, Anne

Purpose: To prospectively determine the effect of deodorant use on acute skin toxicity and quality of life during breast radiotherapy (RT). Methods and Materials: Before breast RT, 84 patients were randomly assigned to the deodorant group (n = 40) or the no-deodorant group (n = 44). The patients were stratified by axillary RT and previous chemotherapy. Toxicity evaluations were always performed by the principal investigator, who was unaware of the group assignment, at the end of RT and 2 weeks after completion using the Radiation Therapy Oncology Group acute skin toxicity criteria. Symptoms of acute skin toxicity (i.e., discomfort, pain,more » pruritus, sweating) and quality of life were self-evaluated. For each criterion, the point estimate of rate difference with the 95% one-sided upper confidence limit was computed. To claim noninferiority owing to deodorant use, the 95% one-sided upper confidence limit had to be lower than the noninferiority margin, fixed to 12.8%. Results: In the deodorant vs. no-deodorant groups, Grade 2 axillary radiodermatitis occurred in 23% vs. 30%, respectively, satisfying the statistical criteria for noninferiority (p = .019). Grade 2 breast radiodermatitis occurred in 30% vs. 34% of the deodorant vs. no-deodorant groups, respectively, also satisfying the statistical criteria for noninferiority (p = .049). Similar results were observed for the self-reported evaluations. The deodorant group reported less sweating (18% vs. 39%, p = .032). No Grade 3 or 4 radiodermatitis was observed. Conclusion: According to our noninferiority margin definition, the occurrence of skin toxicity and its related symptoms were statistically equivalent in both groups. No evidence was found to prohibit deodorant use (notwithstanding the use of an antiperspirant with aluminum) during RT for breast cancer.« less

Raster-scanned carbon ion therapy for malignant salivary gland tumors: acute toxicity and initial treatment response

PubMed Central

2011-01-01

Background and purpose To investigate toxicity and efficacy in high-risk malignant salivary gland tumors (MSGT) of the head and neck. Local control in R2-resected adenoid cystic carcinoma was already improved with a combination of IMRT and carbon ion boost at only mild side-effects, hence this treatment was also offered to patients with MSGT and microscopic residual disease (R1) or perineural spread (Pn+). Methods From November 2009, all patients with MSGT treated with carbon ion therapy were evaluated. Acute side effects were scored according to CTCAE v.4.03. Tumor response was assessed according to RECIST where applicable. Results 103 patients were treated from 11/2009 to 03/2011, median follow-up is 6 months. 60 pts received treatment following R2 resections or as definitive radiation, 43 patients received adjuvant radiation for R1 and/or Pn+. 16 patients received carbon ion treatment for re-irradiation. Median total dose was 73.2 GyE (23.9 GyE carbon ions + 49,9 Gy IMRT) for primary treatment and 44.9 GyE carbon ions for re-irradiation. All treatments were completed as planned and generally well tolerated with no > CTC°III toxicity. Rates of CTC°III toxicity (mucositis and dysphagia) were 8.7% with side-effects almost completely resolved at first follow-up. 47 patients showed good treatment responses (CR/PR) according to RECIST. Conclusion Acute toxicity remains low in IMRT with carbon ion boost also in R1-resected patients and patients undergoing re-irradiation. R2-resected patients showed high rates of treatment response, though follow-up is too short to assess long-term disease control. PMID:22046954

Clinical and laboratory findings of rhabdomyolysis in opioid overdose patients in the intensive care unit of a poisoning center in 2014 in Iran

PubMed Central

Babak, Khoshideh; Mohammad, Arefi; Mazaher, Ghorbani; Fatemeh, Taghizadeh

2017-01-01

OBJECTIVES The aim of this study was to investigate the clinical and demographic characteristics and some laboratory findings of hospitalized patients with acute opioid toxicity and rhabdomyolysis. METHODS This cross-sectional study investigated 354 patients hospitalized at Baharloo Hospital in Tehran in 2014 with acute illicit drug toxicity. Data were collected using an investigator-made checklist. The collected data (such as mortality rate, demographic data, and renal function tests, as well as serum biochemical findings) were analyzed by descriptive statistics and the chi-square test. RESULTS A total of 354 patients were admitted to the hospital in 2014 with acute illicit drug toxicity, including 291 males and 63 females. The total number of patients with rhabdomyolysis was 76 (21.5% of the total), of whom 69 (90.8%) were male and 7 (9.2%) were female. Most cases of rhabdomyolysis were associated with methadone abuse, followed by opium abuse. Rhabdomyolysis was most common in those 20-29 and 30-39 years old, with methadone and opium the most commonly abused illicit drugs. The mean blood urea level was 3.8±1.0 mg/dL, and the mean serum potassium and sodium levels were 3.8±0.3 mg/dL and 140.4±4.0 mg/dL, respectively. Five patients, all of whom were male, passed away due to severe renal failure (6.5%). CONCLUSIONS Toxicity caused by opioids is associated with clinical complications and laboratory disorders, such as electrolyte disorders, which can lead to lethal or life-threatening results in some cases. Abnormal laboratory test findings should be identified in patients with opioid toxicity in order to initiate efficient treatment. PMID:29121712

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

PubMed Central

2014-01-01

Background Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. Methods A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy\\1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. Results 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Conclusions Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group. PMID:24485047

Development of an acceptable factor to estimate chronic end points from acute toxicity data

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

Venman, B.C.; Flaga, C.

1985-12-01

Acceptable daily intake (ADI) values are routinely developed for threshold toxicants from NOAELs determined from human or animal chronic or subchronic data. These NOAELs are then divided by appropriate uncertainty factors ranging from 10 to 1000 depending on the quality of the data. However, for the vast majority of chemicals used industrially, adequate toxicity data needed to use this process are not available. Thus, a procedure to estimate a chronic toxicity endpoint from acute toxicity data, such as an oral rat LD50, becomes necessary. An acute-to-chronic application factor of 0.0001 was developed, which when multiplied by an oral LD50 formore » an individual chemical, yields a surrogate chronic NOAEL. This figure can then be used to estimate an acceptable daily exposure for humans. The process used to estimate this application factor is detailed.« less

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

PubMed

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

2016-02-01

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

AQUIRE: Aquatic Toxicity Information Retrieval data base. Data file

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

Anderson, E.; Pilli, A.

The purpose of Aquatic Toxicity Information Retrieval (AQUIRE) data base is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for AQUIRE. Independently compiled data files that meet AQUIRE parameter and quality assurance criteria are also included. Selected toxicity-test results and related testing information for any individual chemical from laboratory and field aquatic toxicity tests are extracted and added to AQUIRE. Acute, sublethal, and bioconcentration effects are included for tests withmore » freshwater and marine organisms. The total number of data records in AQUIRE now equals 104,500. This includes data from 6000 references, for 5200 chemicals and 2400 test species. A major data file, Acute Toxicity of Organic Chemicals (ATOC), has been incorporated into AQUIRE. The ATOC file contains laboratory acute test data on 525 organic chemicals using juvenile fathead minnows. The complete data file can be accessed by requesting review code 5 as a search parameter.« less

Toxicity and bioaccumulation of sediment-associated contaminants using freshwater invertebrates: A review of methods and applications

USGS Publications Warehouse

Ingersoll, C.G.; Ankley, G.T.; Benoit, D.A.; Brunson, E.L.; Burton, G.A.; Dwyer, F.J.; Hoke, R.A.; Landrum, P.F.; Norberg-King, T. J.; Winger, P.V.

1995-01-01

This paper reviews recent developments in methods for evaluating the toxicity and bioaccumulation of contaminants associated with freshwater sediments and summarizes example case studies demonstrating the application of these methods. Over the past decade, research has emphasized development of more specific testing procedures for conducting 10-d toxicity tests with the amphipod Hyalella azteca and the midge Chironomus tentans. Toxicity endpoints measured in these tests are survival for H. azteca and survival and growth for C. tentans. Guidance has also been developed for conducting 28-d bioaccumulation tests with the oligochaete Lumbriculus variegatus, including determination of bioaccumulation kinetics for different compound classes. These methods have been applied to a variety of sediments to address issues ranging from site assessments to bioavailability of organic and inorganic contaminants using field-collected and laboratory-spiked samples. Survival and growth of controls routinely meet or exceed test acceptability criteria. Results of laboratory bioaccumulation studies with L. variegatus have been confirmed with comparisons to residues (PCBs, PAHs, DDT) present from synoptically collected field populations of oligochaetes. Additional method development is currently underway to develop chronic toxicity tests and to provide additional data-confirming responses observed in laboratory sediment tests with natural benthic populations.

Multiple factors govern the association between pharmacology and toxicity in a class of drugs: toward a unification of class effect terminology.

PubMed

Smith, Dennis A; Harrison, Anthony; Morgan, Paul

2011-04-18

The term class effect has gained in use to describe a side effect including toxicity common to a series of drugs. There is no definition of what constitutes a class effect, and it is not applied against a rigid set of criteria.Thus, the finding of toxicity in one of a series of drugs can raise the concern of a class effect, especially if one or more of the others shows findings even slightly related or at very much lower incidence. This is particularly problematic when the term is used loosely or speculatively on initial events that are themselves of low incidence and serious. This speculation exaggerates and distorts the scientific process in establishing the true benefit risk of the individual drugs and can lead to lengthy development times, or highly restrictive labeling, to the detriment of patient welfare. To provide better definition and application of the term, we suggest that the term class effect toxicity is only used when a clear mechanistic link has been established between a safety concern and drug class based on (I) where the primary pharmacology delivers a clear rationale for the observed findings and toxicities; and (II) where the secondary pharmacology is obligate to the class of the molecule and not subject to variation of structure, and the selectivity cannot be impacted significantly by variations in potency introduced by structural manipulation. With these categorizations, we believe class effect toxicity will be mainly confined to I with examples such as the tetracycline class of antibacterials which inhibit protein synthesis both as a mechanism of antibacterial activity and to produce hepatic injury by mitochondrial injury in the liver.

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

40 CFR 799.9120 - TSCA acute dermal toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... identification number. A system to randomly assign animals to test groups and control groups is required. (E... source of test animals. (2) Method of randomization in assigning animals to test and control groups. (3... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS...

Tolerance and dose-volume relationship of intrathoracic stomach irradiation after esophagectomy for patients with thoracic esophageal squamous cell carcinoma

PubMed Central

Fu, Xiao-Long; Chen, Jun-Chao; Xiang, Jia-Qing

2015-01-01

Purpose To identify the tolerance of radiation with a high prescribed dose and predictors for the development of intrathoracic stomach toxicity in patients with thoracic esophageal squamous cell carcinoma (SCC) after esophagectomy followed by gastric conduit reconstruction. Methods and Materials From 2011 to 2013, 105 patients after esophagectomy were treated with postoperative radiotherapy. The intrathoracic stomach was outlined with the calculation of a dose-volume histogram (DVH) for the initial intended treatment of 6020 cGy or 6300 cGy. The volume of the intrathoracic stomach receiving each dose was recorded at 10-Gy intervals between 10 and 40 Gy and at 5-Gy intervals between 40 and 60 Gy. The grade of toxicities was defined by the National Cancer Institute Common Toxicity Criteria version 4.0. Results The mean and maximum doses of the intrathoracic stomach were 2449 ± 986 cGy and 6519 ± 406 cGy, respectively. Sixteen (15.2%) and three (2.9%) experienced Common Toxicity Criteria Grade 2 and Grade 3 acute gastric toxicity. There were no Grade 4 toxicities. Fourteen patients (13.3%) exhibited late gastric complications possibly related to radiation. The volume percent of the intrathoracic stomach receiving at least 50 Gy (V50) was strongly associated with the degree of toxicity (p = 0.024, respectively). Multivariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicities. Conclusions The intrathoracic stomach is well tolerated with a high-dose irradiation for patients with esophageal SCC receiving radiotherapy after esophagectomy. A strong dose-volume relationship exists for the development of Grade 2 acute intrathoracic stomach toxicity in our study. PMID:26314958

Toxicity Assessment of Wild Mushrooms from the Western Ghats, India: An in Vitro and Sub-Acute in Vivo Study

PubMed Central

Sai Latha, S.; Naveen, S.; Pradeep, C. K.; Sivaraj, C.; Dinesh, M. G.; Anilakumar, K. R.

2018-01-01

Background: Poisoning by different kinds of toxic mushrooms is unfortunately becoming an increasingly important medical problem, evident from the growing number of reports worldwide since the 1950s. Mycetism being a health concern, deserves scientific attention. In this perspective, the present study aims to assess the potential effects of ingesting the selected wild mushrooms from regions of the Western Ghats, India. Methods: The preliminary cytotoxicity of the selected mushrooms was studied in vitro on the intestinal NCM460 and the Chang's liver cell lines on the basis of cell viability. Further, the hepatotoxicity was assessed by measuring biologically relevant endpoints such as membrane integrity, mitochondrial stress and oxidative status. A 28 day sub-acute toxicity study was carried out by orally administering the mushroom extracts to mice at 250 and 500 mg/kg body weight. The hematological and serum analysis as well as histological examinations were carried out to evaluate their in vivo toxicity. GC-MS analysis of the mushrooms facilitated the identification of their volatile chemical profile. Result: The in vitro intestinal cytotoxicity exhibited by these wild mushrooms in comparison to the edible mushroom indicated their potential gastrointestinal toxicity. The pathological findings in small intestine on exposure to Chlorophyllum molybdites and Agaricus endoxanthus also validates the speculations about their intestinal toxicity. The toxic insult to the hepatocytes due to Amanita angustilamellata, Entoloma crassum, and Clarkeinda trachodes was predictive of the observed in vivo hepatotoxicity which was also accompanied by renal toxicity at the higher dose of 500 mg/kg bwt. Conclusion: The potential toxicity exhibited by these representative mushrooms from the wild warrants caution about their consumption. The present work could also have broader implications for global mycetism. PMID:29487528

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

EPA Science Inventory

Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

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

EPA Science Inventory

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

ACUTE TOXICITY OF PARA-NONYLPHENOL TO SALTWATER ANIMALS

EPA Science Inventory

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

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement.

PubMed

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). In vivo toxicity studies were performed in male balb 'C' mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement.

Contrasting effects of chloride on growth, reproduction, and toxicant sensitivity in two genetically distinct strains of Hyalella azteca.

PubMed

Soucek, David J; Mount, David R; Dickinson, Amy; Hockett, J Russell; McEwen, Abigail R

2015-10-01

The strain of Hyalella azteca (Saussure: Amphipoda) commonly used for aquatic toxicity testing in the United States has been shown to perform poorly in some standardized reconstituted waters frequently used for other test species. In 10-d and 42-d experiments, the growth and reproduction of the US laboratory strain of H. azteca was shown to vary strongly with chloride concentration in the test water, with declining performance observed below 15 mg/L to 20 mg/L. In contrast to the chloride-dependent performance of the US laboratory strain of H. azteca, growth of a genetically distinct strain of H. azteca obtained from an Environment Canada laboratory in Burlington, Ontario, Canada, was not influenced by chloride concentration. In acute toxicity tests with the US laboratory strain of H. azteca, the acute toxicity of sodium nitrate increased with decreasing chloride in a pattern similar not only to that observed for control growth, but also to previous acute toxicity testing with sodium sulfate. Subsequent testing with the Burlington strain showed no significant relationship between chloride concentration and the acute toxicity of sodium nitrate or sodium sulfate. These findings suggest that the chloride-dependent toxicity shown for the US laboratory strain may be an unusual feature of that strain and perhaps not broadly representative of aquatic organisms as a whole. © 2015 SETAC.

Dermal toxicity, eye and dermal irritation and skin sensitization evaluation of a new formulation of Bacillus thuringiensis var israelensis SH-14.

PubMed

Arteaga, M E; Mancebo, A; Molier, T; Gómez, D; González, C; Bada, A M; González, B; Rojas, N M; Rodríguez, G

2014-02-01

Bacillus thuringiensis (Bt) is the best known and most widely used of all pesticidal microbes. The aim of this study was to assess the toxicity of a new formulation of Bacillus thuringiensis var israelensis SH-14 in rats through acute dermal toxicity, dermal and eye irritation experiments. The acute dermal toxicity and dermal and eye irritation studies were performed using rabbits according to the United States Environmental Protection Agency guidelines 885.3100, 870.2500 and 870.2500, respectively. The skin sensitization study was carried out in accordance to the EPA OPPTS 870.2600 using guinea pigs. There was no mortality and no evidence of treatment-related toxicity in acute dermal toxicity test. No dermal responses, including erythema/eschar or edema, were found in rabbits treated with the new formulation of Bti SH-14. Minimum response was observed after eye application of test substance. No skin sensitization reactions were observed after the challenge with the new formulation of Bti SH-14 in the Bti SH-14-treated guinea pigs. In summary, the present study demonstrated that the new formulation of Bti SH-14 is not acutely toxic via dermal route, has low eye irritation and would not cause dermal irritation or hypersensitivity to tested animals. Copyright © 2013 Elsevier Inc. All rights reserved.

Acute Toxicity and Cytotoxicity of Pereskia aculeata, a Highly Nutritious Cactaceae Plant.

PubMed

Silva, Debora O; Seifert, Mauricio; Nora, Fabiana R; Bobrowski, Vera L; Freitag, Rogerio A; Kucera, Heidi R; Nora, Leonardo; Gaikwad, Nilesh W

2017-04-01

Pereskia aculeata is a Cactaceae plant with valuable nutritional properties, including terrific amounts of protein, minerals, vitamins, and fiber. However, P. aculeata is reported to contain antinutrients and alkaloids in its leaves. In addition, in a study on growth and development, Wistar rats fed with P. aculeata and casein as protein source grew less than the control group (fed with casein only). Therefore, in this study, we evaluated, for the first time, the oral acute toxicity of P. aculeata in rats and also the cytotoxicity behavior of the plant on lettuce seeds. The acute toxicity research was carried out using dried P. aculeata ethanolic extract, in three different doses, administered by gavage to 24 female Wistar rats. The rats were then examined for signs of toxicity, food intake, body weight, and fecal excretion fluctuations, as well as histopathological alterations, using eight different body tissues. The acute toxicity study did not show any difference among the groups in either clinical evaluation or histopathological analyses. For the cytotoxicity study, dried P. aculeata ethanolic extract was applied on lettuce seeds in five different concentrations. These seeds were evaluated for germination, root and shoot length, and mitotic index. The results show that P. aculeata extract affects lettuce root and shoot growth, but not germination or mitotic index. In conclusion, the acute toxicity on rats and the cytogenotoxicity on lettuce of P. aculeata are neglectable, validating the potential of this plant to be used as a functional food.

Impact of glyphosate and glyphosate-based herbicides on the freshwater environment.

PubMed

Annett, Robert; Habibi, Hamid R; Hontela, Alice

2014-05-01

Glyphosate [N-(phosphonomethyl) glycine] is a broad spectrum, post emergent herbicide and is among the most widely used agricultural chemicals globally. Initially developed to control the growth of weed species in agriculture, this herbicide also plays an important role in both modern silviculture and domestic weed control. The creation of glyphosate tolerant crop species has significantly increased the demand and use of this herbicide and has also increased the risk of exposure to non-target species. Commercially available glyphosate-based herbicides are comprised of multiple, often proprietary, constituents, each with a unique level of toxicity. Surfactants used to increase herbicide efficacy have been identified in some studies as the chemicals responsible for toxicity of glyphosate-based herbicides to non-target species, yet they are often difficult to chemically identify. Most glyphosate-based herbicides are not approved for use in the aquatic environment; however, measurable quantities of the active ingredient and surfactants are detected in surface waters, giving them the potential to alter the physiology of aquatic organisms. Acute toxicity is highly species dependant across all taxa, with toxicity depending on the timing, magnitude, and route of exposure. The toxicity of glyphosate to amphibians has been a major focus of recent research, which has suggested increased sensitivity compared with other vertebrates due to their life history traits and reliance on both the aquatic and terrestrial environments. This review is designed to update previous reviews of glyphosate-based herbicide toxicity, with a focus on recent studies of the aquatic toxicity of this class of chemicals. Copyright © 2014 John Wiley & Sons, Ltd.

Acute eosinophilic pneumonia secondary to heroin inhalation.

PubMed

Eyüpoğlu, Damla; Ortaç Ersoy, Ebru; Rollas, Kazım; Topeli, Arzu

2017-06-01

Smoking heroin (chasing the dragon), is a method of inhaling heroin via heating the drug on a tin-foil above a flame. It also has been associated both with the indirect effects of heroin overdose and with direct pulmonary toxicity. We describe a case of acute eosinophilic pneumonia secondary to heroin inhalation in our medical intensive care unit. She presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed bilateral infiltrations. Examination of bronchoalveolar lavage fluid revealed significant eosinophilia. She was diagnosed with acute eosinophilic pneumonia. After heroin abstinence and corticosteroid therapy, remission was achieved rapidly and the patient was discharge on the fourth day of her hospital stay.

Toxicity potential of disinfection agent in tannery wastewater.

PubMed

Tisler, Tatjana; Zagorc-Koncan, Jana; Cotman, Magda; Drolc, Andreja

2004-09-01

Wastewater from a tannery was investigated using chemical-specific analyses and assessment of the acute toxicity of the whole effluent over a 2-year period. The wastewater samples were overloaded with organic and inorganic compounds, and measured concentrations of the chemical parameters as well as dilution factors estimating acute toxicity, frequently exceeded the permissible limits for the discharge of wastewater from a tannery into the receiving stream. In the later part of the monitoring programme, the toxicity of the samples was significantly increased in comparison to the previous samples. The agent for hide disinfection was assumed to be the reason for the increased toxicity of the wastewater samples, and the extremely high acute and chronic toxicity of the agent to bacteria, algae, daphnids, and fish confirmed this suspicion. The most sensitive species was Daphnia magna; the 48 h EC50 was 0.70 x 10(-5)v/v% and the 21d IC25 was 0.40 x 10(-6)v/v% of the agent. After withdrawal of this highly toxic agent for hide disinfection from the technological process in the tannery, the toxicity of the wastewater declined to the previous level.

The mysid Siriella armata as a model organism in marine ecotoxicology: comparative acute toxicity sensitivity with Daphnia magna.

PubMed

Pérez, Sara; Beiras, Ricardo

2010-01-01

Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (\\24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers (microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20 degrees C, with 16 h light: 8 h dark photoperiod for 96 h. Each neonate was fed daily with 10-15 nauplii of Artemia salina. Acute (96 h) LC50 values, in increasing order, were 46.9 lg/L for Cu, 99.3 lg/L for Cd, 466.7 lg/L for Zn and 8.5 mg/L for SDS. The LC(10), NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC(50) values were 56.2 lg/L for Cu, 571.5 lg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests.

Combinatorial QSAR Modeling of Rat Acute Toxicity by Oral Exposure

EPA Science Inventory

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

Toxicity study of Vernonia cinerea.

PubMed

Latha, L Yoga; Darah, I; Jain, K; Sasidharan, S

2010-01-01

The methanol extract of Vernonia cinerea Less (Asteraceae), which exhibited antimicrobial activity, was tested for toxicity. In an acute toxicity study using mice, the median lethal dose (LD(50)) of the extract was greater than 2000 mg/kg, and we found no pathological changes in macroscopic examination by necropsy of mice treated with extract. As well as the oral acute toxicity study, the brine shrimp lethality test was also done. Brine shrimp test LC(50) values were 3.87 mg/mL (6 h) and 2.72 mg/mL (24 h), exhibiting no significant toxicity result. In conclusion, the methanol extract of V. cinerea did not produce toxic effects in mice and brine shrimp.

Acute toxicity of two generic drilling fluids and six additives, alone and combined, to mysids (Mysidopsis bahia)

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

Parrish, P.R.; Macauley, J.M.; Montgomery, R.M.

1988-01-01

Toxicity tests were conducted with two laboratory-prepared generic drilling fluids (muds) and six commonly used drilling-fluid additives to determine their toxicity, alone and combined, to mysids (Mysidopsis bahia). In 25 tests, the acute toxicity of combinations of one, two, or three of the drilling-fluid additives mixed with either drilling fluid was less than the toxicity predicted from the empirical 96-h LC50s for drilling fluid additive(s) and/or drilling fluid alone; the observed 96-h LC50s of the mixtures were from 1.3 to 23.6 times the values predicted from the presumption of additive toxicity.

Glossary of Aquatic Ecological Terms,

DTIC Science & Technology

1972-02-01

changes. ACUTE TOXICITY Any toxic effect that is produced within a short period of time, usually 24-96 hours. Although the effect most frequently...considered is mortality, the end result of acute toxicity is not necessarily death. Any harmful biolopical effect may be the result. (See Chronic...manufacture of organic compounds within an organism. (See Metabolism ) 4. *1 -ib- ~:2~ ’ A- 3 I ANADROHOUS Pertaining to fishes that speid most of their

Effects of TNT leakage from dumped ammunition on fish and invertebrates in static brackish water systems.

PubMed

Ek, Helene; Nilsson, Eva; Dave, Göran

2008-01-01

The objective of the present study was to study the release and effect of TNT from dumped ammunition. Cleaved artillery shells were placed in static brackish water systems for 5 months, and another 12 months with 5 cm sediment burial. The toxicity was determined in bioassays with crustaceans (Nitocra spinipes and Hyalella azteca) and/or European flounder (Platichtys flesus). The water phase was analysed for TNT using colorimetric method and GC-MS. This study showed a rapid release of TNT to acutely toxic concentrations when the cleaved ammuniton was not covered with sediment under static conditions, but that the release was effectively inhibited by sediment burial of the artillery shells. Hence, at least in a short-term perspective, acute adverse effects of sediment-buried ammunition on aquatic organisms should be greatly reduced.

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

EPA Science Inventory

Abstract for presentation

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

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

Sediment quality assessment using survival and embryo malformation tests in amphipod crustaceans: The Gulf of Riga, Baltic Sea AS case study

NASA Astrophysics Data System (ADS)

Strode, Evita; Jansons, Mintauts; Purina, Ingrida; Balode, Maija; Berezina, Nadezhda A.

2017-08-01

The aim of this study was to assess the toxicity of bottom sediment and to estimate the potential effects of contaminated sediment on health of benthic organisms in the Gulf of Riga (eastern Baltic Sea). Two endpoints were used: survival rate (acute toxicity test) of five crustacean amphipod species and frequency of embryo malformation (samples were collected from the field) in the two species. Toxic resistance of living animals to sediment quality was measured as survival rate (%) at 25 study sites from 2010-2012. Significant differences in the toxic resistance between species were found: 80-100% for Monoporeia affinis, 70-95% for Corophium volutator, 38-88% for Pontogammarus robustoides, 38-100% for Bathyporeia pilosa and 60-100% for Hyalella azteca. Reproductive disorders, measured as percentage (%) of malformed embryos per female, varied in the ranges of 0.0-9.5% in deep water species M. affinis and 0.3-7.5% in littoral species P. robustoides. Both the acute toxicity test and embryo malformation test (only M. affinis was used) indicated moderate and poor sediment quality at 20% and 12% accordingly in the study sites, low toxicity of sediment was estimated in 64% of cases, and no toxicity was recorded in the rest of the cases (4%). Additionally, sediment toxicity test using aquatic organisms was combined with sediment chemical analysis (trace metals) and the Benthic Quality Index (macrozoobenthos) was based on data collected from 13 sites in the Gulf of Riga in 2010 and used for triad sediment quality assessment. According to this combined approach, 23% of the bottom sediments were classified as likely impacted and 23% as possibly impacted (central and southern part of the Gulf). However, the remaining 54% was identified as likely un-impacted. The sediment quality assessment with single survival test or chemical analyses showed better sediment quality in the Gulf than the triad method. The embryo malformation test appeared to be more sensitive to pollution than acute toxicity survival test, that allow us to recommend the inclusion of this novel biomarker in environmental monitoring, while combining it with other tests. In general, our results indicate good or moderate states of sediments and minimal effects of the toxic contamination in them on the Gulf of Riga ecosystem.

Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

PubMed Central

Sim, K. S.; Sri Nurestri, A. M.; Sinniah, S. K.; Kim, K. H.; Norhanom, A. W.

2010-01-01

Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

PubMed

Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

2014-12-01

A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies. Copyright © 2014 Elsevier Inc. All rights reserved.

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

USGS Publications Warehouse

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

2016-01-01

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

Preclinical safety assessments of nano-sized constructs on cardiovascular system toxicity: A case for telemetry.

PubMed

Cheah, Hoay Yan; Kiew, Lik Voon; Lee, Hong Boon; Japundžić-Žigon, Nina; Vicent, Marίa J; Hoe, See Ziau; Chung, Lip Yong

2017-11-01

While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to CVS toxicity. We conclude the review by outlining the merits of telemetry coupled with spectral analysis, baroreceptor reflex sensitivity analysis and echocardiography as an appropriate integrated strategy for the assessment of the acute and chronic impact of NSCs on the CVS. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

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

Amsbaugh, Mark J.; Grosshans, David R., E-mail: dgrossha@mdanderson.org; McAleer, Mary Frances

2012-08-01

Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas,more » and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.« less

Pulmonary toxicity following exposure to a tile coating product containing alkylsiloxanes. A clinical and toxicological evaluation

PubMed Central

Nørgaard, A. W.; Hansen, J. S.; Sørli, J. B.; Jacobsen, P.; Lynggard, F.; Levin, M.; Nielsen, G. D.; Wolkoff, P.; Ebbehøj, N. E.; Larsen, S. T.

2014-01-01

Context Coating products are widely used for making surfaces water and dirt repellent. However, on several occasions the use of these products has been associated with lung toxicity. Objective In the present study, we evaluated the toxic effects of an aerosolized tile-coating product. Methods Thirty-nine persons, who reported respiratory and systemic symptoms following exposure to the tile-coating product, were clinically examined. The product was analysed chemically and furthermore, the exposure scenario was reconstructed using a climate chamber and the toxicological properties of the product were studied using in vivo and by in vitro surfactometry. Results The symptoms developed within few hours and included coughing, tachypnoea, chest pain, general malaise and fever. The physical examination revealed perihilar lung infiltrates on chest radiograph and reduced blood oxygen saturation. The acute symptoms resolved gradually within 1–3 days and no delayed symptoms were observed. By means of mass spectrometry and X-ray spectroscopy, it was shown that the product contained non-fluorinated alkylsiloxanes. The exposure conditions in the supermarket were reconstructed under controlled conditions in a climate chamber and particle and gas exposure levels were monitored over time allowing estimation of human exposure levels. Mice exposed to the product developed symptoms of acute pulmonary toxicity in a concentration-and time-dependent manner. The symptoms of acute pulmonary toxicity likely resulted from inhibition of the pulmonary surfactant function as demonstrated by in vitro surfactometry. Among these patients only a partial association between the level of exposure and the degree of respiratory symptoms was observed, which could be because of a high inter-individual difference in sensitivity and time-dependent changes in the chemical composition of the aerosol. Conclusion Workers need to cautiously apply surface coating products because the contents can be highly toxic through inhalation, and the aerosols can disperse to locations remote from the worksite and affect bystanders. PMID:24815546

Early Clinical Outcome With Concurrent Chemotherapy and Extended-Field, Intensity-Modulated Radiotherapy for Cervical Cancer

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

Beriwal, Sushil; Gan, Gregory N.; Heron, Dwight E.

2007-05-01

Purpose: To assess the early clinical outcomes with concurrent cisplatin and extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix. Methods and Materials: Thirty-six patients with Stage IB2-IVA cervical cancer treated with EF-IMRT were evaluated. The pelvic lymph nodes were involved in 19 patients, and of these 19 patients, 10 also had para-aortic nodal disease. The treatment volume included the cervix, uterus, parametria, presacral space, upper vagina, and pelvic, common iliac, and para-aortic nodes to the superior border of L1. Patients were assessed for acute toxicities according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0.more » All late toxicities were scored with the Radiation Therapy Oncology Group late toxicity score. Results: All patients completed the prescribed course of EF-IMRT. All but 2 patients received brachytherapy. Median length of treatment was 53 days. The median follow-up was 18 months. Acute Grade {>=}3 gastrointestinal, genitourinary, and myelotoxicity were seen in 1, 1, and 10 patients, respectively. Thirty-four patients had complete response to treatment. Of these 34 patients, 11 developed recurrences. The first site of recurrence was in-field in 2 patients (pelvis in 1, pelvis and para-aortic in 1) and distant in 9 patients. The 2-year actuarial locoregional control, disease-free survival, overall survival, and Grade {>=}3 toxicity rates for the entire cohort were 80%, 51%, 65%, and 10%, respectively. Conclusion: Extended-field IMRT with concurrent chemotherapy was tolerated well, with acceptable acute and early late toxicities. The locoregional control rate was good, with distant metastases being the predominant mode of failure. We are continuing to accrue a larger number of patients and longer follow-up data to further extend our initial observations with this approach.« less

Soil bioretention protects juvenile salmon and their prey from the toxic impacts of urban stormwater runoff.

PubMed

McIntyre, J K; Davis, J W; Hinman, C; Macneale, K H; Anulacion, B F; Scholz, N L; Stark, J D

2015-08-01

Green stormwater infrastructure (GSI), or low impact development, encompasses a diverse and expanding portfolio of strategies to reduce the impacts of stormwater runoff on natural systems. Benchmarks for GSI success are usually framed in terms of hydrology and water chemistry, with reduced flow and loadings of toxic chemical contaminants as primary metrics. Despite the central goal of protecting aquatic species abundance and diversity, the effectiveness of GSI treatments in maintaining diverse assemblages of sensitive aquatic taxa has not been widely evaluated. In the present study we characterized the baseline toxicity of untreated urban runoff from a highway in Seattle, WA, across six storm events. For all storms, first flush runoff was toxic to the daphniid Ceriodaphnia dubia, causing up to 100% mortality or impairing reproduction among survivors. We then evaluated whether soil media used in bioretention, a conventional GSI method, could reduce or eliminate toxicity to juvenile coho salmon (Oncorhynchus kisutch) as well as their macroinvertebrate prey, including cultured C. dubia and wild-collected mayfly nymphs (Baetis spp.). Untreated highway runoff was generally lethal to salmon and invertebrates, and this acute mortality was eliminated when the runoff was filtered through soil media in bioretention columns. Soil treatment also protected against sublethal reproductive toxicity in C. dubia. Thus, a relatively inexpensive GSI technology can be highly effective at reversing the acutely lethal and sublethal effects of urban runoff on multiple aquatic species. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acute lethal toxicity, hyperkalemia associated with renal injury and hepatic damage after intravenous administration of cadmium nitrate in rats.

PubMed

Dote, Emi; Dote, Tomotaro; Shimizu, Hiroyasu; Shimbo, Yukari; Fujihara, Michiko; Kono, Koichi

2007-01-01

Cadmium nitrate Cd(NO(3))(2) (CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD(50) of CdN was determined to be 5.5 mg/kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-beta-D-glucosaminidase/creatinine, beta(2)-microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN.

A Qualitative Analysis of Acute Skin Toxicity among Breast Cancer Radiotherapy Patients

PubMed Central

Schnur, Julie B.; Ouellette, Suzanne C.; DiLorenzo, Terry A.; Green, Sheryl; Montgomery, Guy H.

2013-01-01

Objectives One of the most common acute side effects of breast cancer radiotherapy is treatment induced skin changes, referred to as skin toxicity. Yet no research to date has focused expressly on skin toxicity-related quality of life in breast cancer radiotherapy patients. Therefore, our aim was to use qualitative approaches to better understand the impact of skin toxicity on quality of life. Methods Semi-structured interviews were conducted with 20 women (Stage 0-III breast cancer), during their last week of external beam radiotherapy. Each interview was transcribed verbatim, and thematic analysis was performed. Results Three themes were identified based on the interview responses: First, skin changes affect multiple dimensions of quality of life. They cause physical discomfort, body image disturbance, emotional distress, and impair both day-to-day functioning and satisfaction with radiation treatment. Second, individual differences affect women’s experiences. Generally African-American women, younger women, women who are not currently in a relationship, women who are being treated during the summer, and women who are more invested in their appearance are more distressed by skin toxicity. Third, women use a variety of symptom management strategies including self-medication, complementary/alternative medicine approaches, and psychological strategies. Conclusions Implications of results are: 1) Skin toxicity affects numerous dimensions of quality of life, and assessment approaches and psychosocial interventions should address this; 2) individual differences may affect the experience of skin toxicity, and should be considered in treatment and education approaches; and 3) participants’ own creativity and problem-solving should be used to improve the treatment experience. PMID:20238306

Antifouling Activity of Synthetic Alkylpyridinium Polymers Using the Barnacle Model

PubMed Central

Piazza, Veronica; Dragić, Ivanka; Sepčić, Kristina; Faimali, Marco; Garaventa, Francesca; Turk, Tom; Berne, Sabina

2014-01-01

Polymeric alkylpyridinium salts (poly-APS) isolated from the Mediterranean marine sponge, Haliclona (Rhizoniera) sarai, effectively inhibit barnacle larva settlement and natural marine biofilm formation through a non-toxic and reversible mechanism. Potential use of poly-APS-like compounds as antifouling agents led to the chemical synthesis of monomeric and oligomeric 3-alkylpyridinium analogues. However, these are less efficient in settlement assays and have greater toxicity than the natural polymers. Recently, a new chemical synthesis method enabled the production of poly-APS analogues with antibacterial, antifungal and anti-acetylcholinesterase activities. The present study examines the antifouling properties and toxicity of six of these synthetic poly-APS using the barnacle (Amphibalanus amphitrite) as a model (cyprids and II stage nauplii larvae) in settlement, acute and sub-acute toxicity assays. Two compounds, APS8 and APS12-3, show antifouling effects very similar to natural poly-APS, with an anti-settlement effective concentration that inhibits 50% of the cyprid population settlement (EC50) after 24 h of 0.32 mg/L and 0.89 mg/L, respectively. The toxicity of APS8 is negligible, while APS12-3 is three-fold more toxic (24-h LC50: nauplii, 11.60 mg/L; cyprids, 61.13 mg/L) than natural poly-APS. This toxicity of APS12-3 towards nauplii is, however, 60-fold and 1200-fold lower than that of the common co-biocides, Zn- and Cu-pyrithione, respectively. Additionally, exposure to APS12-3 for 24 and 48 h inhibits the naupliar swimming ability with respective IC50 of 4.83 and 1.86 mg/L. PMID:24699112

ESTIMATION OF ACUTE TOXICITY BY FITTING A DOSE-TIME RESPONSE SURFACE

EPA Science Inventory

In acute toxicity testing, organisms are continuously exposed to progressively increasing concentrations of a chemical and deaths of test organisms are recorded at several selected times. he results of the test are traditionally summarized by a dose-response curve, and the time c...

EVALUATION OF MINIMUM DATA REQUIREMENTS FOR ACUTE TOXICITY VALUE EXTRAPOLATION WITH AQUATIC ORGANISMS

EPA Science Inventory

Buckler, Denny R., Foster L. Mayer, Mark R. Ellersieck and Amha Asfaw. 2003. Evaluation of Minimum Data Requirements for Acute Toxicity Value Extrapolation with Aquatic Organisms. EPA/600/R-03/104. U.S. Environmental Protection Agency, National Health and Environmental Effects Re...

COMPARATIVE TOXICITY OF FLUORANTHENE TO FRESHWATER AND SALTWATER SPECIES UNDER FLUORESCENT AND ULTRAVIOLET LIGHT

EPA Science Inventory

The acute and chronic toxicity of fluoranthene was determined for a diverse group of freshwater and saltwater species under both standard laboratory fluorescent light and ultraviolet (UV) light test conditions. Acute tests with 21 species demonstrated that fluoranthene was not le...