40 CFR Appendix V to Part 265 - Examples of Potentially Incompatible Waste

Code of Federal Regulations, 2011 CFR

2011-07-01

... pressure, (2) fire or explosion, (3) violent reaction, (4) toxic dusts, mists, fumes, or gases, or (5... analyze his wastes so that he can avoid creating uncontrolled substances or reactions of the type listed... mixed in a way that precludes a reaction (e.g., adding acid to water rather than water to acid) or that...

40 CFR Appendix V to Part 264 - Examples of Potentially Incompatible Waste

Code of Federal Regulations, 2011 CFR

2011-07-01

... explosion, (3) violent reaction, (4) toxic dusts, mists, fumes, or gases, or (5) flammable fumes or gases... can avoid creating uncontrolled substances or reactions of the type listed below, whether they are... precludes a reaction (e.g., adding acid to water rather than water to acid) or that neutralizes them (e.g...

Evaluation of an alternative in vitro test battery for detecting reproductive toxicants in a grouping context.

PubMed

Kroese, E Dinant; Bosgra, Sieto; Buist, Harrie E; Lewin, Geertje; van der Linden, Sander C; Man, Hai-yen; Piersma, Aldert H; Rorije, Emiel; Schulpen, Sjors H W; Schwarz, Michael; Uibel, Frederik; van Vugt-Lussenburg, Barbara M A; Wolterbeek, Andre P M; van der Burg, Bart

2015-08-01

Previously we showed a battery consisting of CALUX transcriptional activation assays, the ReProGlo assay, and the embryonic stem cell test, and zebrafish embryotoxicity assay as 'apical' tests to correctly predict developmental toxicity for 11 out of 12 compounds, and to explain the one false negative [7]. Here we report on applying this battery within the context of grouping and read across, put forward as a potential tool to fill data gaps and avoid animal testing, to distinguish in vivo non- or weak developmental toxicants from potent developmental toxicants within groups of structural analogs. The battery correctly distinguished 2-methylhexanoic acid, monomethyl phthalate, and monobutyltin trichloride as non- or weak developmental toxicants from structurally related developmental toxicants valproic acid, mono-ethylhexyl phthalate, and tributyltin chloride, respectively, and, therefore, holds promise as a biological verification model in grouping and read across approaches. The relevance of toxicokinetic information is indicated. Copyright © 2014 Elsevier Inc. All rights reserved.

Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose.

PubMed

Wu, Ming-Ling; Deng, Jou-Fang

2011-01-01

Both moclobemide and fluoxetine are used in the treatment of depression, and have been shown to produce fewer side effects than conventional tricyclic antidepressants. A combination of moclobemide and fluoxetine has been used in refractory depression, however there is potential for severe serotonin toxicity. We describe a lethal case of serotonin toxicity in a 36 year-old woman after she ingested multiple drugs, including moclobemide 4500 mg, fluoxetine 200 mg, propranolol 300 mg and several benzodiazepines. The clinical features included coma, mydriasis, hyperthermia, tremor, hyperreflexia, rhabdomyolysis, renal failure and respiratory insufficiency. Eventually, the patient died of disseminated intravascular coagulation and circulatory collapse at 22.5 h postingestion. Toxicological analysis of the patient's blood confirmed high levels of moclobemide 150 μg/mL (therapeutic 1-3 μg/mL), fluoxetine 3750 ng/mL (therapeutic 47-469 ng/mL) and several benzodiazepines. In conclusion, a combination of moclobemide and fluoxetine should be avoided in depressed patients with high suicidal tendencies. Moreover, early recognition and aggressive intervention are the mainstays in the management of potentially life-threatening serotonin toxicity.

Evaluation of toxic and genotoxic potential of a wet gas scrubber effluent obtained from wooden-based biomass furnaces: A case study in the red ceramic industry in southern Brazil.

PubMed

Bortolotto, Tiago; da Silva, Jaqueline; Sant'Ana, Alex Célio; Tomazi, Kamila Osowski; Geremias, Reginaldo; Angioletto, Elídio; Pich, Claus Tröger

2017-09-01

Red ceramic industry in southern Brazil commonly uses wood biomass as furnace fuel generating great amounts of gas emissions and ash. To avoid their impact on atmospheric environment, wet scrubbing is currently being applied in several plants. However, the water leachate formed could be potentially toxic and not managed as a common water-based effluent, since the resulting wastewater could carry many toxic compounds derived from wood pyrolysis. There is a lack of studies regarding this kind of effluent obtained specifically and strictly from wooden-based biomass furnaces. Therefore, we conducted an evaluation of toxic and genotoxic potentials of this particular type of wet gas scrubber effluent. Physical-chemical analysis showed high contents of several contaminants, including phenols, sulphates and ammoniacal nitrogen, as well as the total and suspended solids. The effluent cause significant toxicity towards microcrustacean Artemia sp. (LC 50 = 34.4%) and Daphnia magna (Toxicity Factor = 6 on average) and to higher plants (Lactuca sativa L. and Allium cepa L.) with acute and sub-acute effects in several parameters. Besides, using plasmid DNA, significant damage was observed in concentrations 12.5% and higher. In cellular DNA, concentrations starting from 12.5% and 6.25% showed significant increase in Damage Index (DI) and Damage Frequency (DF), respectively. The results altogether suggest that the effluent components, such phenols, produced by wood combustion can be volatilized, water scrubbed, resulting in a toxic and genotoxic effluent which could contaminate the environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential toxicity of improperly discarded exhausted photovoltaic cells.

PubMed

Motta, C M; Cerciello, R; De Bonis, S; Mazzella, V; Cirino, P; Panzuto, R; Ciaravolo, M; Simoniello, P; Toscanesi, M; Trifuoggi, M; Avallone, B

2016-09-01

Low tech photovoltaic panels (PVPs) installed in the early '80s are now coming to the end of their life cycle and this raises the problem of their proper disposal. As panels contain potentially toxic elements, unconventional, complex and costly procedures are required to avoid environmental health risks and in countries where environmental awareness and economic resources are limited this may be especially problematic. This work was designed to investigate potential risks from improper disposal of these panels. To accomplish this aim an exhausted panel was broken into pieces and these were placed in water for 30 days. The resulting leached solution was analyzed to determine chemical release or used in toto, to determine its potential toxicity in established tests. The end points were seed germination (on Cucumis sativus and Lens culinaris) and effects on early development in three larval models: two crustaceans, Daphnia magna and Artemia salina, and the sea urchin Paracentrotus lividus. Our results show that the panels release small amounts of electrolytes (Na, Ca and Mg) into solution, along with antimony and manganese, with a concentration under the accepted maximum contaminant level, and nickel at a potentially toxic concentration. Developmental defects are seen in the plant and animal test organisms after experimental exposure to the whole solution leached from the broken panel. The toxic effects revealed in in vitro tests are sufficient to attract attention considering that they are exerted on both plants and aquatic animals and that the number of old PVPs in disposal sites will be very high. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adverse interaction between colchicine and ketoconazole in a Chinese shar pei.

PubMed

McAlister, Amber; Center, Sharon A; Bender, Hannah; McDonough, Sean P

2014-01-01

A Chinese shar pei with a 2 yr history of episodic fever, lethargy, and shifting lameness was presumptively diagnosed with familial shar pei fever but had never been treated for the syndrome. After being presented for a superficial pyoderma with possible dermatophyte coinfection, treatment with a cephalosporin and ketoconazole were prescribed. One wk later, colchicine was initiated for familial shar pei fever using cautious dose escalation. Nevertheless, gastrointestinal toxicity, skeletal muscle myopathy, and hepatotoxicity developed within 2 wk. Abrupt resolution of gastrointestinal toxicity and myopathy followed drug withdrawal. However, escalating liver enzyme activity and hyperbilirubinemia led to liver biopsy to rule out an antecedent hepatopathy. Biopsy characterized canalicular cholestasis and colchicine-associated metaphase arrest and ring mitoses reflecting repression of mitotic spindle formation. Signs of illness completely resolved 3 mo after drug discontinuation. Although avoidable adverse interactions between ketoconazole and drugs reliant on cytochrome oxidase biotransformation and/or drug efflux mediated by multiple drug-resistant transporters are well documented in humans, these are rarely reported in veterinary patients. This case exemplifies an important and avoidable ketoconazole/colchicine drug interaction from which the patient completely recovered. The dog tested negative for the canine MDR1 loss of function mutation that also might potentiate colchicine toxicity.

Environmental assessment of depleted uranium used in military armor-piercing rounds in terrestrial systems.

PubMed

Stanley, Jacob K; Coleman, Jessica G; Brasfield, Sandra M; Bednar, Anthony J; Ang, Choo Y

2014-06-01

Depleted uranium (DU) from the military testing and use of armor-piercing kinetic energy penetrators has been shown to accumulate in soils; however, little is known about the toxicity of DU geochemical species created through corrosion or weathering. The purpose of the present study was to assess the toxic effects and bioaccumulation potential of field-collected DU oxides to the model terrestrial invertebrates Eisenia fetida (earthworm) and Porcellio scaber (isopod). Earthworm studies were acute (72 h) dermal exposures or 28-d spiked soil exposures that used noncontaminated field-collected soils from the US Army's Yuma and Aberdeen Proving Grounds. Endpoints assessed in earthworm testing included bioaccumulation, growth, reproduction, behavior (soil avoidance), and cellular stress (neutral red uptake in coelomocytes). Isopod testing used spiked food, and endpoints assessed included bioaccumulation, survival, and feeding behavior. Concentration-dependent bioaccumulation of DU in earthworms was observed with a maximum bioaccumulation factor of 0.35; however, no significant reductions in survival or impacts to cellular stress were observed. Reproduction lowest-observed-effect concentrations (LOEC) of 158 mg/kg and 96 mg/kg were observed in Yuma Proving Ground and a Mississippi reference soil (Karnac Ferry), respectively. Earthworm avoidance of contaminated soils was not observed in 48-h soil avoidance studies; however, isopods were shown to avoid food spiked with 12.7% by weight DU oxides through digital tracking studies. © 2014 SETAC.

Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida.

PubMed

Rico, Andreu; Sabater, Consuelo; Castillo, María-Ángeles

2016-05-01

The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure period of 2 days; and mortality, weight loss, enzymatic activities (cholinesterase, lactate dehydrogenase and alkaline phosphatase) and histopathological effects after an exposure period of 14 days. Carbendazim was found to be highly toxic to E. fetida (LC50=2mg/kg d.w.), significantly reducing earthworm weight and showing an avoidance response at soil concentrations that are close to those predicted in rice-fields and in surrounding ecosystems. The insecticide dimethoate showed a moderate acute toxicity (LC50=28mg/kg d.w.), whereas the rest of tested pesticides showed low toxicity potential (LC50 values above 100mg/kg d.w.). For these pesticides, however, weight loss was identified as a sensitive endpoint, with NOEC values approximately 2 times or lower than the calculated LC10 values. The investigated effects on the enzymatic activities of E. fetida and the observed histopathological alterations (longitudinal and circular muscle lesions, edematous tissues, endothelial degeneration and necrosis) proved to be sensitive biomarkers to monitor pesticide contamination and are proposed as alternative measures to evaluate pesticide risks on agro-ecosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

Linking waterlogging tolerance with Mn²⁺ toxicity: a case study for barley.

PubMed

Huang, X; Shabala, S; Shabala, L; Rengel, Z; Wu, X; Zhang, G; Zhou, M

2015-01-01

Vast agricultural areas are affected by flooding, causing up to 80% yield reduction and resulting in multibillion dollar losses. Up to now, the focus of plant breeders was predominantly on detrimental effects of anoxia, while other (potentially equally important) traits were essentially neglected; one of these is soil elemental toxicity. Excess water triggers a progressive decrease in soil redox potential, thus increasing the concentration of Mn(2+) that can be toxic to plants if above a specific threshold. This work aimed to quantify the relative contribution of Mn(2+) toxicity to waterlogging stress tolerance, using barley as a case study. Twenty barley (Hordeum vulgare) genotypes contrasting in waterlogging stress tolerance were studied for their ability to cope with toxic (1 mm) amounts of Mn(2+) in the root rhizosphere. Under Mn(2+) toxicity, chlorophyll content of most waterlogging-tolerant genotypes (TX9425, Yerong, CPI-71284-48 and CM72) remained above 60% of the control value, whereas sensitive genotypes (Franklin and Naso Nijo) had 35% less chlorophyll than 35% of controls. Manganese concentration in leaves was not related to visual Mn(2+) toxicity symptoms, suggesting that various Mn(2+) tolerance mechanisms might operate in different tolerant genotypes, i.e. avoidance versus tissue tolerance. The overall significant (r = 0.60) correlation between tolerance to Mn(2+) toxicity and waterlogging in barley suggests that plant breeding for tolerance to waterlogging traits may be advanced by targeting mechanisms conferring tolerance to Mn(2+) toxicity, at least in this species. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Intra-cerebral schwannoma simulating glioma.

PubMed

Louis, Elie; Cret, Corina; Poirier, Jacques; Cornu, Philippe; Martin-Duverneuil, Nadine; Delattre, Jean-Yves; Sanson, Marc

2003-09-01

An intra-cerebral schwannoma, presenting as a cystic, calcified, enhancing frontal mass, arising in a 52-year-old woman was misdiagnosed as a glioma and treated with radiotherapy. This observation emphasizes the importance of careful histological reexamination of all brain tumors when a discrepancy appears between the initial histological diagnosis and the clinical evolution, in order to recognize rare curable entities and to avoid potentially toxic treatment.

Mutagenicity and Acute Oral Toxicity Test for Herbal Poultry Feed Supplements.

PubMed

Srinivasa Rao, Boddapati; Chandrasekaran, C V; Srikanth, H S; Sasikumar, Murugan; Edwin Jothie, R; Haseena, Begum; Bharathi, Bethapudi; Selvam, Ramasamy; Prashanth, D'Souza

2018-01-01

Herbal products are being used and trusted globally for thousands of years for their health benefits and limited side effects. Globally, a general belief amongst the consumers is that herbal supplements are always safe because they are "natural." But later, research reveals that they may not be safe. This raises concern on their safety and implications for their use as feed supplement or medicine. Toxicity testing can reveal some of the risks that may be associated with use of herbs, therefore avoiding potential harmful effects. The present study was designed to investigate five poultry feed supplements (PFS), EGMAX® (to revitalize ovarian activity), FEED-X ™ (feed efficiency enhancer), KOLIN PLUS ™ (natural replacer of synthetic choline chloride), PHYTOCEE® (natural defence enhancer), and STODI® (to prevent and control loose droppings), for their possible mutagenicity and toxicity. Bacterial reverse mutation (BRMT) and acute oral toxicity tests were employed to assess the PFS for their possible mutagenicity and toxicity. Results indicated that the PFS were devoid of mutagenic effects in BRMT and showed higher safety profile in rodent acute oral toxicity test.

Environmental Benefits and Burdens of Phosphorus Recovery from Municipal Wastewater.

PubMed

Bradford-Hartke, Zenah; Lane, Joe; Lant, Paul; Leslie, Gregory

2015-07-21

The environmental benefits and burdens of phosphorus recovery in four centralized and two decentralized municipal wastewater systems were compared using life cycle assessment (LCA). In centralized systems, phosphorus recovered as struvite from the solids dewatering liquid resulted in an environmental benefit except for the terrestrial ecotoxicity and freshwater eutrophication impact categories, with power and chemical use offset by operational savings and avoided fertilizer production. Chemical-based phosphorus recovery, however, generally required more resources than were offset by avoided fertilizers, resulting in a net environmental burden. In decentralized systems, phosphorus recovery via urine source separation reduced the global warming and ozone depletion potentials but increased terrestrial ecotoxicity and salinization potentials due to application of untreated urine to land. Overall, mineral depletion and eutrophication are well-documented arguments for phosphorus recovery; however, phosphorus recovery does not necessarily present a net environmental benefit. While avoided fertilizer production does reduce potential impacts, phosphorus recovery does not necessarily offset the resources consumed in the process. LCA results indicate that selection of an appropriate phosphorus recovery method should consider both local conditions and other environmental impacts, including global warming, ozone depletion, toxicity, and salinization, in addition to eutrophication and mineral depletion impacts.

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

Proof of Principle of Ocular sparing in dogs with sinonasal tumors treated with intensity-modulated radiation therapy

PubMed Central

Lawrence, Jessica A.; Forrest, Lisa J.; Turek, Michelle M.; Miller, Paul E.; Mackie, T. Rockwell; Jaradat, Hazim A.; Vail, David M.; Dubielzig, Richard R.; Chappell, Richard; Mehta, Minesh P.

2010-01-01

Intensity modulated radiation therapy (IMRT) allows optimization of radiation dose delivery to complex tumor volumes with rapid dose drop-off to surrounding normal tissues. A prospective study was performed to evaluate the concept of conformal avoidance using IMRT in canine sinonasal cancer. The potential of IMRT to improve clinical outcome with respect to acute and late ocular toxicity was evaluated. Thirty-one dogs with sinonasal cancer were treated definitively with IMRT using helical tomotherapy and/or dynamic multileaf collimator (DMLC) delivery. Ocular toxicity was evaluated prospectively and compared to a comparable group of historical controls treated with conventional two-dimensional radiotherapy (2D-RT) techniques. Treatment plans were devised for each dog using helical tomotherapy and DMLC that achieved the target dose to the planning treatment volume and limited critical normal tissues to the prescribed dose-volume constraints. Overall acute and late toxicities were limited and minor, detectable by an experienced observer. This was in contrast to the profound ocular morbidity observed in the historical control group treated with 2D-RT. Overall median survival for IMRT treated and 2D treated dogs was 420 days and 411 days, respectively. Compared with conventional techniques, IMRT reduced dose delivered to eyes and resulted in bilateral ocular sparing in the dogs reported herein. These data provide proof-of-principle that conformal avoidance radiotherapy can be delivered through high conformity IMRT, resulting in decreased normal tissue toxicity as compared to historical controls treated with 2D-RT. PMID:20973393

Oxygen toxicity.

PubMed

Stogner, S W; Payne, D K

1992-12-01

The objective of this article is to provide an overview of the biochemistry of oxygen metabolism, including the formation of free radicals and the role of endogenous antioxidants. Pathophysiologic correlates underlying the clinical manifestations of oxygen toxicity are reviewed and management strategies are outlined. References from basic science and clinical journals were selected from the authors' files and from a search of a computerized database of the biomedical literature. Articles selected for review included both historical and current literature concerning the biochemistry and pathophysiology of oxygen toxicity in animals and humans. The benefits of oxygen therapy have been known for many years; however, its potential toxicity has not been recognized until the last two decades. The lungs, the eyes, and, under certain conditions, the central nervous system are the organs most affected by prolonged exposure to hyperoxic environments. Free radical formation during cellular metabolism under hyperoxic conditions is recognized as the biochemical basis of oxygen injury to cells and organs. Endogenous antioxidants are a primary means of detoxifying reactive oxygen species and preventing hyperoxia-induced cellular damage. When this defense fails or is overwhelmed by the excessive production of hyperoxia-induced free-radical species, distinctive morphologic changes occur at the cellular level. The amount of hyperoxia required to cause cellular damage and the time course of these changes vary from species to species and from individual to individual within the same species. Age, nutritional status, presence of underlying diseases, and certain drugs may influence the development of oxygen toxicity. There is currently no reliably effective drug for preventing or delaying the development of oxygen toxicity in humans. Use of the lowest effective oxygen concentration, the avoidance of certain drugs, and attention to nutritional and metabolic factors remain the best means currently available to avoid or minimize oxygen toxicity. Research is continuing into more effective ways to prevent, diagnose, and treat this disorder.

How much oxygen in adult cardiac arrest?

PubMed

Dell'Anna, Antonio Maria; Lamanna, Irene; Vincent, Jean-Louis; Taccone, Fabicpro Silvio

2014-10-07

Although experimental studies have suggested that a high arterial oxygen pressure (PaO2) might aggravate post-anoxic brain injury, clinical studies in patients resuscitated from cardiac arrest (CA) have given conflicting results. Some studies found that a PaO2 of more than 300 mm Hg (hyperoxemia) was an independent predictor of poor outcome, but others reported no association between blood oxygenation and neurological recovery in this setting. In this article, we review the potential mechanisms of oxygen toxicity after CA, animal data available in this field, and key human studies dealing with the impact of oxygen management in CA patients, highlighting some potential confounders and limitations and indicating future areas of research in this field. From the currently available literature, high oxygen concentrations during cardiopulmonary resuscitation seem preferable, whereas hyperoxemia should be avoided in the post-CA care. A specific threshold for oxygen toxicity has not yet been identified. The mechanisms of oxygen toxicity after CA, such as seizure development, reactive oxygen species production, and the development of organ dysfunction, need to be further evaluated in prospective studies.

Ecotoxicological characterization of sugarcane vinasses when applied to tropical soils.

PubMed

Alves, Paulo Roger L; Natal-da-Luz, Tiago; Sousa, José Paulo; Cardoso, Elke J B N

2015-09-01

The impact of sugarcane vinasse on soil invertebrates was assessed through ecotoxicological assays. Increasing concentrations of two vinasses from different distillery plants (VA and VB), and a vinasse from a laboratory production (VC), were amended on two natural tropical Oxisols (LV and LVA) and a tropical artificial soil (TAS) to characterize the effects of the vinasses on earthworms (Eisenia andrei), enchytraeids (Enchytraeus crypticus), mites (Hypoaspis aculeifer) and collembolans (Folsomia candida). The highest concentrations of VA and VB were avoided by earthworms in all soils and by collembolans especially in the natural soils. The presence of VC in all of the tested soils did not cause avoidance behavior in these species. The reproduction of earthworms, enchytraeids and collembolans was decreased in the highest concentrations of VA and VB in the natural soils. In TAS, VB reduced the reproduction of all test species, whereas VA was toxic exclusively to E. andrei and E. crypticus. The vinasse VC only reduced the number of earthworms in TAS and enchytraeids in LVA. The reproduction of mites was reduced by VB in TAS. Vinasses from distillery plants were more toxic than the vinasse produced in laboratory. The vinasse toxicities were influenced by soil type, although this result was most likely because of the way the organisms are exposed to the contaminants in the soils. Toxicity was attributed to the vinasses' high salt content and especially the high potassium concentrations. Data obtained in this study highlights the potential risk of vinasse disposal on tropical soils to soil biota. The toxic values estimated are even more relevant when considering the usual continuous use of vinasses in crop productions. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of antimutagenic and genotoxic potential of senna (Cassia angustifolia Vahl.) aqueous extract using in vitro assays.

PubMed

Silva, C R; Monteiro, M R; Rocha, H M; Ribeiro, A F; Caldeira-de-Araujo, A; Leitão, A C; Bezerra, R J A C; Pádula, M

2008-02-01

Senna (Cassia angustifolia Vahl.) is widely used as a laxative, although potential side effects, such as toxicity and genotoxicity, have been reported. This study evaluated genotoxic and mutagenic effects of senna aqueous extract (SAE) by means of four experimental assays: inactivation of Escherichia coli cultures; bacterial growth inhibition; reverse mutation test (Mutoxitest) and DNA strand break analysis in plasmid DNA. Our results demonstrated that SAE produces single and double strand breaks in plasmid DNA in a cell free system. On the other hand, SAE was not cytotoxic or mutagenic to Escherichia coli strains tested. In effect, SAE was able to avoid H(2)O(2)-induced mutagenesis and toxicity in Escherichia coli IC203 (uvrA oxyR) and IC205 (uvrA mutM) strains, pointing to a new antioxidant/antimutagenic action of SAE.

Delivering safer immunotherapies for cancer

PubMed Central

Milling, Lauren; Zhang, Yuan; Irvine, Darrell J.

2017-01-01

Cancer immunotherapy is now a powerful clinical reality, with a steady progression of new drug approvals and a massive pipeline of additional treatments in clinical and preclinical development. However, modulation of the immune system can be a double-edged sword: Drugs that activate immune effectors are prone to serious non-specific systemic inflammation and autoimmune side effects. Drug delivery technologies have an important role to play in harnessing the power of immune therapeutics while avoiding on-target/off-tumor toxicities. Here we review mechanisms of toxicity for clinically-relevant immunotherapeutics, and discuss approaches based in drug delivery technology to enhance the safety and potency of these treatments. These include strategies to merge drug delivery with adoptive cellular therapies, targeting immunotherapies to tumors or select immune cells, and localizing therapeutics intratumorally. Rational design employing lessons learned from the drug delivery and nanomedicine fields has the potential to facilitate immunotherapy reaching its full potential. PMID:28545888

Trace elements in coal. Environmental and health significance

USGS Publications Warehouse

Finkelman, R.B.

1999-01-01

Trace elements can have profound adverse effects on the health of people burning coal in homes or living near coal deposits, coal mines, and coal- burning power plants. Trace elements such as arsenic emitted from coal- burning power plants in Europe and Asia have been shown to cause severe health problems. Perhaps the most widespread health problems are caused by domestic coal combustion in developing countries where millions of people suffer from fluorosis and thousands from arsenism. Better knowledge of coal quality characteristics may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals in coal may help to predict the behavior of the potentially toxic trace metals during coal cleaning, combustion, weathering, and leaching.

Serotonin toxicity caused by moclobemide too soon after paroxetine-selegiline.

PubMed

Wu, Ming-Ling; Deng, Jou-Fang

2009-08-01

Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is due to an overstimulation of central and peripheral serotonin receptors that lead to neuromuscular, mental and autonomic changes. Moclobemide is a reversible inhibitor of monoamine oxidase (MAO)-A, selegiline is an irreversible selective inhibitor of MAO-B, and paroxetine is a selective serotonin reuptake inhibitor. Combined use of these agents is known to cause serotonin toxicity. A 53-year-old woman had been treated with paroxetine and selegiline. After moclobemide was prescribed in place of paroxetine without a washout period, she quickly developed confusion, agitation, ataxia, diaphoresis, tremor, mydriasis, ocular clonus, hyperreflexia, tachycardia, moderately elevated blood pressure and high fever, symptoms that were consistent with serotonin toxicity. Discontinuation of the drugs, hydration and supportive care were followed by remarkable improvement of baseline status within 3 days. This case demonstrates that serotonin toxicity may occur even with small doses of paroxetine, selegiline and moclobemide in combination. Physicians managing patients with depression must be aware of the potential for serotonin toxicity and should be able to recognize and treat or, ideally, anticipate and avoid this pharmacodynamically-mediated interaction that may occur between prescribed drugs.

Integrated Approach of Agri-nanotechnology: Challenges and Future Trends

PubMed Central

Mishra, Sandhya; Keswani, Chetan; Abhilash, P. C.; Fraceto, Leonardo F.; Singh, Harikesh Bahadur

2017-01-01

Nanotechnology representing a new frontier in modern agriculture is anticipated to become a major thrust in near future by offering potential applications. This integrating approach, i.e., agri-nanotechnology has great potential to cope with global challenges of food production/security, sustainability and climate change. However, despite the potential benefits of nanotechnology in agriculture so far, their relevance has not reached up to the field conditions. The elevating concerns about fate, transport, bioavailability, nanoparticles toxicity and inappropriateness of regulatory framework limit the complete acceptance and inclination to adopt nanotechnologies in agricultural sector. Moreover, the current research trends lack realistic approach that fail to attain comprehensive knowledge of risk assessment factors and further toxicity of nanoparticles toward agroecosystem components viz. plant, soil, soil microbiomes after their release into the environment. Hence in the present review we attempt to suggest certain key points to be addressed in the current and future agri-nanotechnology researches on the basis of recognized knowledge gaps with strong recommendation of incorporating biosynthesized nanoparticles to carry out analogous functions. In this perspective, the major points are as follows: (i) Mitigating risk assessment factors (responsible for fate, transport, behavior, bioavailability and toxicity) for alleviating the subsequent toxicity of nanoparticles. (ii) Optimizing permissible level of nanoparticles dose within the safety limits by performing dose dependent studies. (iii) Adopting realistic approach by designing the experiments in natural habitat and avoiding in vitro assays for accurate interpretation. (iv) Most importantly, translating environmental friendly and non-toxic biosynthesized nanoparticles from laboratory to field conditions for agricultural benefits. PMID:28421100

Protective effects of chlorogenic acid in 3-nitropropionic acid induced toxicity and genotoxicity.

PubMed

Alarcón-Herrera, Norberto; Flores-Maya, Saúl; Bellido, Belén; García-Bores, Ana M; Mendoza, Ernesto; Ávila-Acevedo, Guillermo; Hernández-Echeagaray, Elizabeth

2017-11-01

Mitochondrial inhibition with the toxin 3-Nitropropionic acid (3-NP) has been used to study the underlying mechanisms in striatal neurodegeneration, but few experiments have evaluated its toxicity and genotoxicity of in vivo administration. Furthermore, different antioxidant molecules may prevent degeneration induced by the toxic effects of 3-NP. Therefore, the purpose of this study was to evaluate the toxicity and genotoxicity induced by 3-NP (15 mg/kg) in the micronuclei assay method; also, we assessed chlorogenic acid (CGA, 100 mg/kg) for its anti-toxic and anti-genotoxic effect in damage produced by in vivo treatment with 3-NP. 3-NP induced toxicity and genotoxicity. CGA administered as a co-treatment with 3-NP (3-NP + CA) reduced toxicity by 32.76%, as a pre-treatment for 5 days only, followed by 3-NP treatment (P/CA, 3-NP) inhibiting toxicity by 24.04%, or as a pre-treatment, plus a co-treatment with 3-NP (P/CA, 3-NP + CA) avoided any toxic effect. CGA alone did not exhibit any toxic effect. Only P/CGA, 3-NP + CGA group, avoided toxicity and genotoxicity, suggesting that CGA could be suitable to prevent, reduce or delay toxicity and cell death. Copyright © 2017 Elsevier Ltd. 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.

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.

Is the bitter rejection response always adaptive?

PubMed

Glendinning, J I

1994-12-01

The bitter rejection response consists of a suite of withdrawal reflexes and negative affective responses. It is generally assumed to have evolved as a way to facilitate avoidance of foods that are poisonous because they usually taste bitter to humans. Using previously published studies, the present paper examines the relationship between bitterness and toxicity in mammals, and then assesses the ecological costs and benefits of the bitter rejection response in carnivorous, omnivorous, and herbivorous (grazing and browsing) mammals. If the bitter rejection response accurately predicts the potential toxicity of foods, then one would expect the threshold for the response to be lower for highly toxic compounds than for nontoxic compounds. The data revealed no such relationship. Bitter taste thresholds varied independently of toxicity thresholds, indicating that the bitter rejection response is just as likely to be elicited by a harmless bitter food as it is by a harmful one. Thus, it is not necessarily in an animal's best interest to have an extremely high or low bitter threshold. Based on this observation, it was hypothesized that the adaptiveness of the bitter rejection response depends upon the relative occurrence of bitter and potentially toxic compounds in an animal's diet. Animals with a relatively high occurrence of bitter and potentially toxic compounds in their diet (e.g., browsing herbivores) were predicted to have evolved a high bitter taste threshold and tolerance to dietary poisons. Such an adaptation would be necessary because a browser cannot "afford" to reject all foods that are bitter and potentially toxic without unduly restricting its dietary options. At the other extreme, animals that rarely encounter bitter and potentially toxic compounds in their diet (e.g., carnivores) were predicted to have evolved a low bitter threshold. Carnivores could "afford" to utilize such a stringent rejection mechanism because foods containing bitter and potentially toxic compounds constitute a small portion of their diet. Since the low bitter threshold would reduce substantially the risk of ingesting anything poisonous, carnivores were also expected to have a relatively low tolerance to dietary poisons. This hypothesis was supported by a comparison involving 30 mammal species, in which a suggestive relationship was found between quinine hydrochloride sensitivity and trophic group, with carnivores > omnivores > grazers > browsers. Further support for the hypothesis was provided by a comparison across browsers and grazers in terms of the production of tannin-binding salivary proteins, which probably represent an adaptation for reducing the bitterness and astringency of tannins.(ABSTRACT TRUNCATED AT 400 WORDS)

Assessing the fate and effects of nano aluminum oxide in the terrestrial earthworm, Eisenia fetida.

PubMed

Coleman, Jessica G; Johnson, David R; Stanley, Jacob K; Bednar, Anthony J; Weiss, Charles A; Boyd, Robert E; Steevens, Jeffery A

2010-07-01

Nano-sized aluminum is currently being used by the military and commercial industries in many applications including coatings, thermites, and propellants. Due to the potential for wide dispersal in soil systems, we chose to investigate the fate and effects of nano-sized aluminum oxide (Al2O3), the oxidized form of nano aluminum, in a terrestrial organism. The toxicity and bioaccumulation potential of micron-sized (50-200 microm, nominal) and nano-sized (11 nm, nominal) Al2O3 was comparatively assessed through acute and subchronic bioassays using the terrestrial earthworm, Eisenia fetida. Subchronic (28-d) studies were performed exposing E. fetida to nano- and micron-sized Al2O3-spiked soils to assess the effects of long-term exposure. No mortality occurred in subchronic exposures, although reproduction decreased at >or=3,000 mg/kg nano-sized Al2O3 treatments, with higher aluminum body burdens observed at 100 and 300 mg/kg; no reproductive effects were observed in the micron-sized Al2O3 treatments. In addition to toxicity and bioaccumulation bioassays, an acute (48-h) behavioral bioassay was conducted utilizing a soil avoidance wheel in which E. fetida were given a choice of habitat between control, nano-, or micron-sized Al2O3 amended soils. In the soil avoidance bioassays, E. fetida exhibited avoidance behavior toward the highest concentrations of micron- and nano-sized Al2O3 (>5,000 mg/kg) relative to control soils. Results of the present study indicate that nano-sized Al2O3 may impact reproduction and behavior of E. fetida, although at high levels unlikely to be found in the environment. Copyright (c) 2010 SETAC.

Worms taste bitter: ASH neurons, QUI-1, GPA-3 and ODR-3 mediate quinine avoidance in Caenorhabditis elegans

PubMed Central

Hilliard, Massimo A; Bergamasco, Carmela; Arbucci, Salvatore; Plasterk, Ronald HA; Bazzicalupo, Paolo

2004-01-01

An animal's ability to detect and avoid toxic compounds in the environment is crucial for survival. We show that the nematode Caenorhabditis elegans avoids many water-soluble substances that are toxic and that taste bitter to humans. We have used laser ablation and a genetic cell rescue strategy to identify sensory neurons involved in the avoidance of the bitter substance quinine, and found that ASH, a polymodal nociceptive neuron that senses many aversive stimuli, is the principal player in this response. Two G protein α subunits GPA-3 and ODR-3, expressed in ASH and in different, nonoverlapping sets of sensory neurons, are necessary for the response to quinine, although the effect of odr-3 can only be appreciated in the absence of gpa-3. We identified and cloned a new gene, qui-1, necessary for quinine and SDS avoidance. qui-1 codes for a novel protein with WD-40 domains and which is expressed in the avoidance sensory neurons ASH and ADL. PMID:14988722

Best Practices in Cancer Nanotechnology – Perspective from NCI Nanotechnology Alliance

PubMed Central

Zamboni, William C.; Torchilin, Vladimir; Patri, Anil; Hrkach, Jeff; Stern, Stephen; Lee, Robert; Nel, Andre; Panaro, Nicholas J.; Grodzinski, Piotr

2014-01-01

Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics. PMID:22669131

Considerations for Incorporating Bioavailability in Effect-Directed Analysis and Toxicity Identification Evaluation.

EPA Science Inventory

In order to avoid a bias toward highly toxic but poorly bioavailable compounds in the effect-directed analysis (EDA) of soils and sediments, approaches are discussed to consider bioavailability in EDA procedures. In parallel, complimentary approaches for making toxicity identific...

Phenytoin-induced toxic epidermal necrolysis: Review and recommendations

PubMed Central

Al-Quteimat, Osama M.

2016-01-01

Toxic epidermal necrolysis (TEN) is a serious, life-threatening skin reaction characterized by severe exfoliation and destruction of the epidermis of the skin. In most TEN cases, drugs are believed to be the causative agent; antipsychotics, antiepileptics, and other medications such as sulfonamides are among the most common causes of drug-induced TEN. Phenytoin, a commonly prescribed medication for seizure, was found to cause TEN. Evidence-based treatment guidelines are lacking, so the best strategy is to identify and avoid potential risk factors and to provide intensive supportive care. The aim of this literature review is to focus on phenytoin-induced TEN, to explore the risk factors, and to highlight the possible treatment options once phenytoin-induced TEN is confirmed. PMID:27651708

Relative toxicity testing of spacecraft materials. 2: Aircraft materials

NASA Technical Reports Server (NTRS)

Lawrence, W. H.

1980-01-01

The relative toxicity of thermodegradation (pyrolysis/combustion) products of aircraft materials was studied. Two approaches were taken to assess the biological activity of the pyrolysis/combustion products of these materials: (1) determine the acute lethality to rats from inhalation of these pyrolysates and (2) examine the tendency for sublethal exposure to the pyrolysates to disrupt behavioral (shock avoidance) performance of exposed rats. The ralative importance of lethality vs. behavioral effects in selection of a material may be dictated by whether or not individuals potentially exposed to such products, would have an opportunity to escape if they were behaviorally capable of doing so. If so, the second parameter would assume greater importance, but if not the first parameter may be of much greater importance in selecting materials.

Identification and Avoidance of Potential Artifacts and Misinterpretations in Nanomaterial Ecotoxicity Measurements

PubMed Central

2015-01-01

Novel physicochemistries of engineered nanomaterials (ENMs) offer considerable commercial potential for new products and processes, but also the possibility of unforeseen and negative consequences upon ENM release into the environment. Investigations of ENM ecotoxicity have revealed that the unique properties of ENMs and a lack of appropriate test methods can lead to results that are inaccurate or not reproducible. The occurrence of spurious results or misinterpretations of results from ENM toxicity tests that are unique to investigations of ENMs (as opposed to traditional toxicants) have been reported, but have not yet been systemically reviewed. Our objective in this manuscript is to highlight artifacts and misinterpretations that can occur at each step of ecotoxicity testing: procurement or synthesis of the ENMs and assessment of potential toxic impurities such as metals or endotoxins, ENM storage, dispersion of the ENMs in the test medium, direct interference with assay reagents and unacknowledged indirect effects such as nutrient depletion during the assay, and assessment of the ENM biodistribution in organisms. We recommend thorough characterization of initial ENMs including measurement of impurities, implementation of steps to minimize changes to the ENMs during storage, inclusion of a set of experimental controls (e.g., to assess impacts of nutrient depletion, ENM specific effects, impurities in ENM formulation, desorbed surface coatings, the dispersion process, and direct interference of ENM with toxicity assays), and use of orthogonal measurement methods when available to assess ENMs fate and distribution in organisms. PMID:24617739

Toxin constraint explains diet choice, survival and population dynamics in a molluscivore shorebird

PubMed Central

van Gils, Jan A.; van der Geest, Matthijs; Leyrer, Jutta; Oudman, Thomas; Lok, Tamar; Onrust, Jeroen; de Fouw, Jimmy; van der Heide, Tjisse; van den Hout, Piet J.; Spaans, Bernard; Dekinga, Anne; Brugge, Maarten; Piersma, Theunis

2013-01-01

Recent insights suggest that predators should include (mildly) toxic prey when non-toxic food is scarce. However, the assumption that toxic prey is energetically as profitable as non-toxic prey misses the possibility that non-toxic prey have other ways to avoid being eaten, such as the formation of an indigestible armature. In that case, predators face a trade-off between avoiding toxins and minimizing indigestible ballast intake. Here, we report on the trophic interactions between a shorebird (red knot, Calidris canutus canutus) and its two main bivalve prey, one being mildly toxic but easily digestible, and the other being non-toxic but harder to digest. A novel toxin-based optimal diet model is developed and tested against an existing one that ignores toxin constraints on the basis of data on prey abundance, diet choice, local survival and numbers of red knots at Banc d'Arguin (Mauritania) over 8 years. Observed diet and annual survival rates closely fit the predictions of the toxin-based model, with survival and population size being highest in years when the non-toxic prey is abundant. In the 6 of 8 years when the non-toxic prey is not abundant enough to satisfy the energy requirements, red knots must rely on the toxic alternative. PMID:23740782

Toxin constraint explains diet choice, survival and population dynamics in a molluscivore shorebird.

PubMed

van Gils, Jan A; van der Geest, Matthijs; Leyrer, Jutta; Oudman, Thomas; Lok, Tamar; Onrust, Jeroen; de Fouw, Jimmy; van der Heide, Tjisse; van den Hout, Piet J; Spaans, Bernard; Dekinga, Anne; Brugge, Maarten; Piersma, Theunis

2013-07-22

Recent insights suggest that predators should include (mildly) toxic prey when non-toxic food is scarce. However, the assumption that toxic prey is energetically as profitable as non-toxic prey misses the possibility that non-toxic prey have other ways to avoid being eaten, such as the formation of an indigestible armature. In that case, predators face a trade-off between avoiding toxins and minimizing indigestible ballast intake. Here, we report on the trophic interactions between a shorebird (red knot, Calidris canutus canutus) and its two main bivalve prey, one being mildly toxic but easily digestible, and the other being non-toxic but harder to digest. A novel toxin-based optimal diet model is developed and tested against an existing one that ignores toxin constraints on the basis of data on prey abundance, diet choice, local survival and numbers of red knots at Banc d'Arguin (Mauritania) over 8 years. Observed diet and annual survival rates closely fit the predictions of the toxin-based model, with survival and population size being highest in years when the non-toxic prey is abundant. In the 6 of 8 years when the non-toxic prey is not abundant enough to satisfy the energy requirements, red knots must rely on the toxic alternative.

Conditioned flavor aversion and location avoidance in hamsters from toxic extract of tall larkspur (Delphinium barbeyi)

USDA-ARS?s Scientific Manuscript database

Studies were conducted to address conditioned flavour aversion (CFA) and place avoidance learning in hamsters given injections of alkaloid extracts from tall larkspur (Delphinium barbeyi), to determine if larkspur had reinforcing or negative properties sufficient to cause place avoidance or preferen...

Preclinical evaluations of norcantharidin-loaded intravenous lipid microspheres with low toxicity.

PubMed

Lin, Xia; Zhang, Bo; Zhang, Keru; Zhang, Yu; Wang, Juan; Qi, Na; Yang, Shenshen; He, Haibing; Tang, Xing

2012-12-01

The aim of this study was to perform a systematic preclinical evaluation of norcantharidin (NCTD)-loaded intravenous lipid microspheres (NLM). Pharmacokinetics, biodistribution, antitumor efficacy and drug safety assessment (including acute toxicity, subchronic toxicity, hemolysis testing, intravenous stimulation and injection anaphylaxis) of NLM were carried out in comparison with the commercial product disodium norcantharidate injection (NI). The pharmacokinetics of NLM in rats was similar to that of NI, and a non-linear correlation was observed between AUC and dose. A comparable antitumor efficacy of NLM and NI was observed in mice inoculated with A549, BEL7402 and BCAP-37 cell lines. It was worth noting that the NLM produced a lower drug concentration in heart compared with NI, and significantly reduced the cardiac and renal toxicity. The LD(50) of NLM was twice higher than that of NI. In NLM, over 80% of NCTD was loaded in the lipid phase or bound with phospholipids. Thus, NCTD was sequestered by direct contacting with body fluids and largely avoided distribution into tissues, consequently leading to significantly reduced cardiac and renal toxicity. These preclinical results suggested that NLM could be a useful potential carrier for parenteral administration of NCTD, while providing a superior safety profile.

Diet composition modifies the toxicity of repeated soman exposure in rats.

PubMed

Langston, Jeffrey L; Myers, Todd M

2011-12-01

It was previously demonstrated that diet potently modulates the toxic effects of an acute lethal dose of the nerve agent soman. The current investigation was undertaken to examine the influence of diet on the cumulative toxicity of repeated soman administration. Rats were fed one of four distinct diets (standard, choline-enriched, glucose-enriched, or ketogenic) for four weeks prior to and throughout a repeated soman dosing and recovery regimen. Each diet group included animals exposed to an equivalent volume of saline that served as negative controls. In exposure Week 1, animals received three consecutive daily doses of 0.4 LD(50) soman. In exposure Week 2, animals received four consecutive daily doses of 0.5 LD(50) soman. In exposure Week 3, animals received five consecutive daily doses of 0.5 LD(50) soman. Week 4 constituted a post-exposure recovery evaluation. Throughout the experiment, behavioral function was assessed by a discriminated avoidance test that required intact sensory and motor function. Survival and body weight changes were recorded daily. Differences in toxicity as a function of diet composition became apparent during the first week. Specifically, rats fed the glucose-enriched diet showed pronounced intoxication during Week 1, resulting in imperfect survival, weight loss, and deteriorated avoidance performance relative to all other groups. All rats fed the glucose-enriched diet died by the end of exposure Week 2. In contrast, only 10% of animals fed the standard diet died by the end of Week 2. Also in Week 2, weight loss and disrupted avoidance performance were apparent for all groups except for those fed the ketogenic diet. This differential effect of diet composition became even more striking in Week 3 when survival in the standard and choline diet groups approximated 50%, whereas survival equaled 90% in the ketogenic diet group. Avoidance performance and weight loss measures corroborated the differential toxicity observed across diet groups. Upon cessation of soman exposure during the final week, recovery of weight and avoidance performance in survivors was comparable across diet groups. These results systematically replicate previous findings demonstrating that diet composition exacerbates or attenuates toxicity in rodents exposed acutely to organophosphorus compounds. Published by Elsevier B.V.

Hepatic Transcriptome Responses in Mice (Mus musculus) Exposed to the Nafion Membrane and Its Combustion Products

PubMed Central

Feng, Mingbao; Qu, Ruijuan; Habteselassie, Mussie; Wu, Jun; Yang, Shaogui; Sun, Ping; Huang, Qingguo; Wang, Zunyao

2015-01-01

Nafion 117 membrane (N117), an important polymer electrolyte membrane (PEM), has been widely used for numerous chemical technologies. Despite its increasing production and use, the toxicity data for N117 and its combustion products remain lacking. Toxicity studies are necessary to avoid problems related to waste disposal in landfills and incineration that may arise. In this study, we investigated the histopathological alterations, oxidative stress biomarker responses, and transcriptome profiles in the liver of male mice exposed to N117 and its combustion products for 24 days. An ion-chromatography system and liquid chromatography system coupled to a hybrid quadrupole time-of-flight mass spectrometry were used to analyze the chemical compositions of these combustion products. The transcriptomics analysis identified several significantly altered molecular pathways, including the metabolism of xenobiotics, carbohydrates and lipids; signal transduction; cellular processes; immune system; and signaling molecules and interaction. These studies provide preliminary data for the potential toxicity of N117 and its combustion products on living organisms and may fill the information gaps in the toxicity databases for the currently used PEMs. PMID:26057616

Widespread Nanoparticle-Assay Interference: Implications for Nanotoxicity Testing

PubMed Central

Ong, Kimberly J.; MacCormack, Tyson J.; Clark, Rhett J.; Ede, James D.; Ortega, Van A.; Felix, Lindsey C.; Dang, Michael K. M.; Ma, Guibin; Fenniri, Hicham; Veinot, Jonathan G. C.; Goss, Greg G.

2014-01-01

The evaluation of engineered nanomaterial safety has been hindered by conflicting reports demonstrating differential degrees of toxicity with the same nanoparticles. The unique properties of these materials increase the likelihood that they will interfere with analytical techniques, which may contribute to this phenomenon. We tested the potential for: 1) nanoparticle intrinsic fluorescence/absorbance, 2) interactions between nanoparticles and assay components, and 3) the effects of adding both nanoparticles and analytes to an assay, to interfere with the accurate assessment of toxicity. Silicon, cadmium selenide, titanium dioxide, and helical rosette nanotubes each affected at least one of the six assays tested, resulting in either substantial over- or under-estimations of toxicity. Simulation of realistic assay conditions revealed that interference could not be predicted solely by interactions between nanoparticles and assay components. Moreover, the nature and degree of interference cannot be predicted solely based on our current understanding of nanomaterial behaviour. A literature survey indicated that ca. 95% of papers from 2010 using biochemical techniques to assess nanotoxicity did not account for potential interference of nanoparticles, and this number had not substantially improved in 2012. We provide guidance on avoiding and/or controlling for such interference to improve the accuracy of nanotoxicity assessments. PMID:24618833

Release and toxicity comparison between industrial- and ...

EPA Pesticide Factsheets

Many consumer products containing ZnO have raised concern for safety in regards toenvironmental impact and the public health. Widely used sunscreens for protectingagainst UV and avoiding sunburns represent a great exposure to nano-ZnO, one of theingredients commonly applied in sunscreens. Applying nano-products on beaches mayrelease nanoparticles unintentionally into the ocean. Despite the accumulation of suchnano-products in the ocean harming or being detrimental to critical marine organisms,few studies have investigated the release and potential toxicity of nanoparticlesextracted from products and compared them with those from industrial-typenanoparticles. Results show that the cytotoxicity of both industrial- and sunscreenderivednano-ZnO to the marine diatom algae, Thalassiosira pseudonana, increasedas exposure increases over time, as measured by growth inhibition (%) of the algae ata constant concentration of nano-ZnO (10 mg/L). The extent of toxicity appeared to behigher from industrial-type nano-ZnO compared to sunscreen-extracted nano-ZnO,though the extent becomes similar when concentrations increase to 50 mg/L. On theother hand, at a fixed exposure time of 48 hrs, the cytotoxicity increases asconcentrations increase with the higher toxicity shown from the industrial-typecompared to sunscreen-induced nano-ZnO. Results indicate that while industrial-typenano-ZnO shows higher toxicity than sunscreen-derived nano-ZnO, the release andextent of toxicity from n

SU-C-BRA-06: Developing Clinical and Quantitative Guidelines for a 4DCT-Ventilation Functional Avoidance Clinical Trial

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

Vinogradskiy, Y; Waxweiler, T; Diot, Q

Purpose: 4DCT-ventilation is an exciting new imaging modality that uses 4DCTs to calculate lung ventilation. Because 4DCTs are acquired as part of routine care, calculating 4DCT-ventilation allows for lung function evaluation without additional cost or inconvenience to the patient. Development of a clinical trial is underway at our institution to use 4DCT-ventilation for thoracic functional avoidance with the idea that preferential sparing of functional lung regions can decrease pulmonary toxicity. The purpose of our work was to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial including: 1.assessing patient eligibility 2.developing trial inclusion criteria and 3.developing treatment planningmore » and dose-function evaluation strategies. Methods: 96 stage III lung cancer patients from 2 institutions were retrospectively reviewed. 4DCT-ventilation maps were calculated using the patient’s 4DCTs, deformable image registrations, and a density-change-based algorithm. To assess patient eligibility and develop trial inclusion criteria we used an observer-based binary end point noting the presence or absence of a ventilation defect and developed an algorithm based on the percent ventilation in each lung third. Functional avoidance planning integrating 4DCT-ventilation was performed using rapid-arc and compared to the patient’s clinically used plan. Results: Investigator-determined clinical ventilation defects were present in 69% of patients. Our regional/lung-thirds ventilation algorithm identified that 59% of patients have lung functional profiles suitable for functional avoidance. Compared to the clinical plan, functional avoidance planning was able to reduce the mean dose to functional lung by 2 Gy while delivering comparable target coverage and cord/heart doses. Conclusions: 4DCT-ventilation functional avoidance clinical trials have great potential to reduce toxicity, and our data suggest that 59% of lung cancer patients have lung function profiles suitable for functional avoidance. Our study used a retrospective evaluation of a large lung cancer patient database to develop the practical aspects of a 4DCT-ventilation functional avoidance clinical trial. (R.C., E.C., T.G.), NIH Research Scientist Development Award K01-CA181292 (R.C.), and State of Colorado Advanced Industries Accelerator Grant (Y.V.)« less

Effect of qualitative and quantitative variation in allelochemicals on a generalist insect: Iridoid glycosides and the southern armyworm.

PubMed

Puttick, G M; Bowers, M D

1988-01-01

The behavioral and physiological effects of plant allelochemicals have been difficult to demonstrate; it is not often clear whether the compounds are deterrent, toxic, or both. In this study, we compared the qualitative and quantitative effects of several iridoid glycosides on a generalist lepidopteran herbivore,Spodoptera eridania (Noctuidae). Larval growth and survivorship and larval preference or avoidance were measured on artificial diets containing different iridoid glycosides at different concentrations. We also tested the toxicity/deterrence of these compounds. We found that iridoid glycosides retarded larval growth significantly at relatively low concentrations and that they were usually avoided in preference tests. The toxicity/ deterrence test did not always reflect the results of these other tests. The merits of using a variety of methods for determining deterrence and/or toxicity of plant allelochemicals are discussed.

Nonprescription analgesics and their use in solid-organ transplantation: a review.

PubMed

Gabardi, Steven; Luu, Linh

2004-09-01

To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. English-language studies were selected for inclusion. Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction. A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

Ecotoxicological assessment of a high energetic and insensitive munitions compound: 2,4-dinitroanisole (DNAN).

PubMed

Dodard, Sabine G; Sarrazin, Manon; Hawari, Jalal; Paquet, Louise; Ampleman, Guy; Thiboutot, Sonia; Sunahara, Geoffrey I

2013-11-15

The high explosive nitroaromatic 2,4-dinitroanisole (DNAN) is less shock sensitive than 2,4,6-trinitrotoluene (TNT), and is proposed as a TNT replacement for melt-cast formulations. Before using DNAN in munitions and potentially leading to environmental impact, the present study examines the ecotoxicity of DNAN using selected organisms. In water, DNAN decreased green algae Pseudokirchneriella subcapitata growth (EC50 = 4.0mg/L), and bacteria Vibrio fischeri bioluminescence (Microtox, EC50 = 60.3mg/L). In soil, DNAN decreased perennial ryegrass Lolium perenne growth (EC50 =7 mg/kg), and is lethal to earthworms Eisenia andrei (LC50 = 47 mg/kg). At sub-lethal concentrations, DNAN caused an avoidance response (EC50 = 31 mg/kg) by earthworms. The presence of DNAN and 2-amino-4-nitroanisole in earthworms and plants suggested a role of these compounds in DNAN toxicity. Toxicity of DNAN was compared to TNT, tested under the same experimental conditions. These analyses showed that DNAN was equally, or even less deleterious to organism health than TNT, depending on the species and toxicity test. The present studies provide baseline toxicity data to increase the understanding of the environmental impact of DNAN, and assist science-based decision makers for improved management of potential DNAN contaminated sites. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Toxic and feeding deterrent effects of native aquatic macrophytes on exotic grass carp (Ctenopharyngodon idella).

PubMed

Murphy, Joseph E; Beckmen, Kimberlee B; Johnson, Julie K; Cope, Rhian B; Lawmaster, Todd; Beasley, Val R

2002-08-01

Declines of amphibians have been attributed to many factors including habitat degradation. The introduction of grass carp (Ctenopharyngodon idella) as a biological agent for aquatic plant control in ponds and lakes managed narrowly for human recreation has likely contributed to amphibian declines through massive plant removal and associated habitat simplification and thus degradation. This research examined the interactions among grass carp and three Midwestern aquatic plants (Jussiaea repens, Ranunculus longirostris, and R. flabellaris) that may be of value in rehabilitation of habitats needed by amphibians. The feeding preference study found that C. idella avoided eating both J. repens and R. longirostris. Ranunculus species studied to date contain a vesicant toxin called ranunculin that is released upon mastication. The study that compared the effects of R. flabellaris, J. repens and a control food administered by tube feeding to C. idella found significant lesions only in the mucosal epithelium of the individuals exposed to R.flabellaris. The avoidance by C. idella of J. repens and R. longirostris in the feeding preference study, and the significant toxicity of R. flabellaris demonstrated by the dosing study, indicate these plants warrant further examination as to their potential effectiveness in aquatic amphibian habitat rehabilitation.

Contribution of individual waste fractions to the environmental impacts from landfilling of municipal solid waste.

PubMed

Manfredi, Simone; Tonini, Davide; Christensen, Thomas H

2010-03-01

A number of LCA-based studies have reported on the environmental performance of landfilling of mixed waste, but little is known about the relative contributions of individual waste fractions to the overall impact potentials estimated for the mixed waste. In this paper, an empirical model has been used to estimate the emissions to the environment from landfilling of individual waste fractions. By means of the LCA-model EASEWASTE, the emissions estimated have been used to quantify how much of the overall impact potential for each impact category is to be attributed to the individual waste fractions. Impact potentials are estimated for 1 tonne of mixed waste disposed off in a conventional landfill with bottom liner, leachate collection and treatment and gas collection and utilization for electricity generation. All the environmental aspects are accounted for 100 years after disposal and several impact categories have been considered, including standard categories, toxicity-related categories and groundwater contamination. Amongst the standard and toxicity-related categories, the highest potential impact is estimated for human toxicity via soil (HTs; 12 mPE/tonne). This is mostly caused by leaching of heavy metals from ashes (e.g. residues from roads cleaning and vacuum cleaning bags), batteries, paper and metals. On the other hand, substantial net environmental savings are estimated for the categories Global Warming (GW; -31 mPE/tonne) and Eco-Toxicity in water chronic (ETwc; -53 mPE/tonne). These savings are mostly determined by the waste fractions characterized by a high content of biogenic carbon (paper, organics, other combustible waste). These savings are due to emissions from energy generation avoided by landfill gas utilization, and by the storage of biogenic carbon in the landfill due to incomplete waste degradation. Copyright 2009 Elsevier Ltd. All rights reserved.

Survival, Reproduction, Avoidance Behavior and Oxidative Stress Biomarkers in the Earthworm Octolasion cyaneum Exposed to Glyphosate.

PubMed

Salvio, Carla; Menone, Mirta L; Rafael, Sergio; Iturburu, Fernando G; Manetti, Pablo L

2016-03-01

The massive use of glyphosate (GLY) in several countries has increased the interest in investigating its potential adverse effects in non-target organisms. The aim of the present study was to assess the potential effects in survival and reproduction; avoidance behavior and oxidative stress under short-term (48 h) and subchronic exposures (28 days) to GLY in the earthworm Octolasion cyaneum. After 48 h no significant changes in the behavior was observed. In addition, a lower catalase activity at 498 μg GLY kg(-1) dry soil section relative to earthworms from the control section was obtained. After 28 days of exposure inhibition of glutathione S-transferase activity was observed at 535 μg GLY kg(-1) dry soil while no changes in the other endpoints were detected. These results indicate that environmentally relevant concentrations of GLY (up to 996 µg GLY kg(-1) dry soil) did not exert a toxic effect to O. cyaneum.

Corneal Injury from Presurgical Chlorhexidine Skin Preparation.

PubMed

Bever, Gregory J; Brodie, Frank L; Hwang, David G

2016-12-01

Chlorhexidine skin preparation has been shown to provide highly effective antimicrobial presurgical skin cleansing. However, there is a significant risk of ocular toxicity when it is used in periocular areas. We describe 2 cases of significant corneal damage resulting from 4% chlorhexidine gluconate preoperative skin cleanser, despite the use of protective occlusive dressing over the eyes. Because of the potential for severe corneal toxicity resulting from use of chlorhexidine, alternative agents such as 10% povidone-iodine should be considered for skin preparation near periocular areas whenever possible. If chlorhexidine gluconate must be employed near periocular areas, great care must be exercised to avoid contact with the eyes, and additional protective measures (e.g., absorbent eye pads along with tightly occlusive dressings) must be used whenever possible. Copyright © 2016 Elsevier Inc. All rights reserved.

Bioassays with terrestrial and aquatic species as monitoring tools of hydrocarbon degradation.

PubMed

Bori, Jaume; Vallès, Bettina; Ortega, Lina; Riva, Maria Carme

2016-09-01

In this study chemical analyses and ecotoxicity tests were applied for the assessment of a heavily hydrocarbon-contaminated soil prior and after the application of a remediation procedure that consisted in the stimulation of soil autochthonous populations of hydrocarbon degraders in static-ventilated biopiles. Terrestrial bioassays were applied in mixtures of test soils and artificial control soil and studied the survival and reproduction of Eisenia fetida and the avoidance response of E. fetida and Folsomia candida. Effects on aquatic organisms were studied by means of acute tests with Vibrio fischeri, Raphidocelis subcapitata, and Daphnia magna performed on aqueous elutriates from test soils. The bioremediation procedure led to a significant reduction in the concentration of hydrocarbons (from 34264 to 3074 mg kg(-1), i.e., 91 % decrease) and toxicity although bioassays were not able to report a percentage decrease of toxicity as high as the percentage reduction. Sublethal tests proved the most sensitive terrestrial bioassays and avoidance tests with earthworms and springtails showed potential as monitoring tools of hydrocarbon remediation due to their high sensitivity and short duration. The concentrations of hydrocarbons in water extracts from test soils were 130 and 100 μg L(-1) before and after remediation, respectively. Similarly to terrestrial tests, most aquatic bioassays detected a significant reduction in toxicity, which was almost negligible at the end of the treatment. D. magna survival was the most affected by soil elutriates although toxicity to the crustacean was associated to the salinity of the samples rather than to the concentration of hydrocarbons. Ecotoxicity tests with aqueous soil elutriates proved less relevant in the assessment of hydrocarbon-contaminated soils due to the low hydrosolubility of hydrocarbons and the influence of the physicochemical parameters of the aquatic medium.

Toxic effects of electrolyte and trace mineral administration in the intensive care unit.

PubMed

Besunder, J B; Smith, P G

1991-07-01

Electrolytes and trace minerals are administered routinely to ICU patients to correct deficiencies or as specific therapy for various conditions. Complications are usually related to the rate of infusion, rapidity of correction of a deficiency state, or iatrogenic poisoning with the agent. Adverse effects associated with Na+ administration included volume overload, CPM, and central nervous system bleeds. The toxic effects of K+, Ca2+, and Mg2+ are primarily related to their effects on the myocardium, nervous system, and muscle. Other than precipitating or maintaining a metabolic acidosis, Cl- administration is relatively nontoxic. Its accompanying anion (i.e., ammonium or arginine), however, may contribute significantly to patient morbidity and, possibly, mortality. Side effects observed with phosphate administration include hypocalcemia, metastatic calcification, and hypernatremia or hyperkalemia. Most of these toxicities are avoidable if appropriate precautions are taken and appropriate monitoring implemented. Finally, when administering any of these agents, the intensivist should be familiar with their toxicologic profiles and management of potential complications.

Defense mechanisms against toxic phytochemicals in the diet of domestic animals.

PubMed

Fink-Gremmels, Johanna

2010-02-01

Plant secondary metabolites (PSMs) are non-nutritional components that occur in numerous feed materials and are able to exert toxic effects in animals. The current article aims to summarize innate defense strategies developed by different animal species to avoid excessive exposure to PSMs. These mechanisms include pre-systemic degradation of PSMs by rumen microbiota, the intestinal barrier including efflux transporters of monogastric species, as well as pre-hepatic and intra-hepatic biotransformation processes. These physiological barriers determine systemic exposure and ultimately the dose-dependent adverse effects in the target animal species. Considering the large number of potentially toxic PSMs, which makes an evaluation of all individual PSMs virtually impossible, such a mechanism-oriented approach could improve the predictability of adverse effects and support the interpretation of clinical field observations. Moreover, mechanistic data related to tissue disposition and excretion pathways of PSMs for example into milk, could substantially support the assessment of the risks for consumers of foods derived from PSM-exposed animals.

Laser ablation ICP-MS profiling and semiquantitative determination of trace element concentrations in desert tortoise shells: documenting the uptake of elemental toxicants.

PubMed

Seltzer, Michaeld; Berry, Kristinh

2005-03-01

The outer keratin layer (scute) of desert tortoise shells consists of incrementally grown laminae in which various bioaccumulated trace elements are sequestered during scute deposition. Laser ablation ICP-MS examination of laminae in scutes of dead tortoises revealed patterns of trace elemental distribution from which the chronology of elemental uptake can be inferred. These patterns may be of pathologic significance in the case of elemental toxicants such as arsenic, which has been linked to both shell and respiratory diseases. Laser ablation transects, performed along the lateral surfaces of sectioned scutes, offered the most successful means of avoiding exogenous contamination that was present on the scute exterior. Semiquantitative determination of elemental concentrations was achieved using sulfur, a keratin matrix element, as an internal standard. The results presented here highlight the potential of laser ablation ICP-MS as a diagnostic tool for investigating toxic element uptake as it pertains to tortoise morbidity and mortality.

Laser ablation ICP-MS profiling and semiquantitative determination of trace element concentrations in desert tortoise shells: Documenting the uptake of elemental toxicants

USGS Publications Warehouse

Seltzer, M.D.; Berry, K.H.

2005-01-01

The outer keratin layer (scute) of desert tortoise shells consists of incrementally grown laminae in which various bioaccumulated trace elements are sequestered during scute deposition. Laser ablation ICP-MS examination of laminae in scutes of dead tortoises revealed patterns of trace elemental distribution from which the chronology of elemental uptake can be inferred. These patterns may be of pathologic significance in the case of elemental toxicants such as arsenic, which has been linked to both shell and respiratory diseases. Laser ablation transects, performed along the lateral surfaces of sectioned scutes, offered the most successful means of avoiding exogenous contamination that was present on the scute exterior. Semiquantitative determination of elemental concentrations was achieved using sulfur, a keratin matrix element, as an internal standard. The results presented here highlight the potential of laser ablation ICP-MS as a diagnostic tool for investigating toxic element uptake as it pertains to tortoise morbidity and mortality.

Effect of selected aldehydes found in the corncob hemicellulose hydrolysate on the growth and xylitol fermentation of Candida tropicalis.

PubMed

Wang, Le; Tang, Pingwah; Fan, Xiaoguang; Yuan, Qipeng

2013-01-01

The effects of four aldehydes (furfural, 5-hydroxymethylfurfural, vanillin and syringaldehyde), which were found in the corncob hemicellulose hydrolysate, on the growth and xylitol fermentation of Candida tropicalis were investigated. The results showed that vanillin was the most toxic aldehyde for the xylitol fermentation, followed by syringaldehyde, furfural and 5-hydroxymethylfurfural. Moreover, the binary combination tests revealed that furfural amplified the toxicity of other aldehydes and the toxicities of other binary combinations without furfural were simply additive. Based on the fermentation experiments, it was demonstrated that the inhibition of aldehydes could be alleviated by prolonging the fermentation incubation, increasing the initial cell concentration, enhancing the initial pH value and minimizing the furfural levels in the hydrolysate evaporation process. The strategies that we proposed to suppress the inhibitory effects of the aldehydes successfully avoided the complicated and costly detoxifications. Our findings could be potentially adopted for the industrial xylitol fermentation from hydrolysates. © 2013 American Institute of Chemical Engineers.

A comparative experimental approach to ecotoxicology in shallow-water and deep-sea holothurians suggests similar behavioural responses.

PubMed

Brown, Alastair; Wright, Roseanna; Mevenkamp, Lisa; Hauton, Chris

2017-10-01

Exploration of deep-sea mineral resources is burgeoning, raising concerns regarding ecotoxicological impacts on deep-sea fauna. Assessing toxicity in deep-sea species is technologically challenging, which promotes interest in establishing shallow-water ecotoxicological proxy species. However, the effects of temperature and hydrostatic pressure on toxicity, and how adaptation to deep-sea environmental conditions might moderate these effects, are unknown. To address these uncertainties we assessed behavioural and physiological (antioxidant enzyme activity) responses to exposure to copper-spiked artificial sediments in a laboratory experiment using a shallow-water holothurian (Holothuria forskali), and in an in situ experiment using a deep-sea holothurian (Amperima sp.). Both species demonstrated sustained avoidance behaviour, evading contact with contaminated artificial sediment. However, A. sp. demonstrated sustained avoidance of 5mgl -1 copper-contaminated artificial sediment whereas H. forskali demonstrated only temporary avoidance of 5mgl -1 copper-contaminated artificial sediment, suggesting that H. forskali may be more tolerant of metal exposure over 96h. Nonetheless, the acute behavioural response appears consistent between the shallow-water species and the deep-sea species, suggesting that H. forskali may be a suitable ecotoxicological proxy for A. sp. in acute (≤24h) exposures, which may be representative of deep-sea mining impacts. No antioxidant response was observed in either species, which was interpreted to be the consequence of avoiding copper exposure. Although these data suggest that shallow-water taxa may be suitable ecotoxicological proxies for deep-sea taxa, differences in methodological and analytical approaches, and in sex and reproductive stage of experimental subjects, require caution in assessing the suitability of H. forskali as an ecotoxicological proxy for A. sp. Nonetheless, avoidance behaviour may have bioenergetic consequences that affect growth and/or reproductive output, potentially impacting fecundity and/or offspring fitness, and thus influencing source-sink dynamics and persistence of wider deep-sea populations. Copyright © 2017 Elsevier B.V. All rights reserved.

A natural agonist of mosquito TRPA1 from the medicinal plant Cinnamosma fragrans that is toxic, antifeedant, and repellent to the yellow fever mosquito Aedes aegypti.

PubMed

Inocente, Edna Alfaro; Shaya, Marguerite; Acosta, Nuris; Rakotondraibe, L Harinantenaina; Piermarini, Peter M

2018-02-01

Plants produce various secondary metabolites that offer a potential source of novel insecticides and repellents for the control of mosquito vectors. Plants of the genus Cinnamosma are endemic to, and widely-distributed throughout, the island of Madagascar. The barks of these species are commonly used in traditional medicines for treating a wide range of maladies. The therapeutic nature of the bark is thought to be associated with its enrichment of pungent drimane sesquiterpenes, which elicit antifeedant and toxic effects in some insects. Here we test the hypothesis that a bark extract of Cinnamosma fragrans (CINEX) and its major drimane sesquiterpenes are insecticidal, antifeedant, and repellent to Aedes aegypti, the principal mosquito vector of chikungunya, dengue, yellow fever, and Zika viruses. We demonstrate that CINEX is 1) toxic to larval and adult female mosquitoes, and 2) antifeedant and repellent to adult female mosquitoes. Moreover, we show that cinnamodial (CDIAL), a sesquiterpene dialdehyde isolated from CINEX, duplicates these bioactivities and exhibits similar toxic potency against pyrethroid-susceptible and -resistant strains of Ae. aegypti. Importantly, we show that CDIAL is an agonist of heterologously-expressed mosquito Transient Receptor Potential A1 (TRPA1) channels, and the antifeedant activity of CDIAL is dampened in a TRPA1-deficient strain of Ae. aegypti (TRPA1-/-). Intriguingly, TRPA1-/- mosquitoes do not exhibit toxic resistance to CDIAL. The data indicate that modulation of TRPA1 is required for the sensory detection and avoidance of CDIAL by mosquitoes, but not for inducing the molecule's toxicity. Our study suggests that CDIAL may serve as a novel chemical platform for the development of natural product-based insecticides and repellents for controlling mosquito vectors.

Escaping from Rejection

PubMed Central

Lynch, Raymond J.; Platt, Jeffrey L.

2009-01-01

Summary Those engaged in clinical transplantation and transplantation immunology have always taken as a central objective the elucidation of means to prevent graft rejection by the recipient immune system. Conceptually, such mechanisms stem from the concept of Paul Ehrlich that all organisms can selectively avoid autotoxicity; i.e. they exhibit horror autotoxicus. Some mechanisms of horror autotoxicus now understood. T lymphocytes and B lymphocytes recognize foreign antigens but not some auto-antigens. Clonal deletion generates lacunae in what is otherwise a virtually limitless potential to recognize antigens. We call this mechanism structural tolerance. Where imperfections in structural tolerance allow self-recognition, the full activation of lymphocytes and generation of effector activity depends on delivery of accessory signals generated by infection and/or injury. The absence of accessory signals prevents or even suppresses immunological responses. We call this dichotomy of responsiveness conditional tolerance. When, despite structural and conditional tolerance, effector activity perturbs autologous cells, metabolism changes in ways that protect against injury. We use the term accommodation to refer to this acquired protection against injury. Structural and conditional tolerance and accommodation overlap in such a way that potentially toxic products can be generated to control microorganisms and neutralize toxins without overly damaging adjacent cells. The central challenge in transplantation, then, should be the orchestration of structural and conditional tolerance and accommodation in such a way that toxic products can still be generated for defense while preserving graft function and survival. Since the earliest days of transplantation, immunobiologists have sought means by which to prevent recognition and rejection of foreign tissue. The goal of these strategies is the retention of recipient immune function while selectively avoiding graft injury. While considerable theoretical and technical problems remain, an analogous problem and solution already exists in nature. Here, we discuss the mechanisms by which organisms preclude or control auto-toxicity, and for each, consider the corollaries between prevention of auto-toxicity and graft rejection. Further study of these controls, including structural and conditional tolerance and accommodation, will offer insight into new therapies for allo- and xenotransplantation. PMID:19996920

Pesticide poisoning.

PubMed

Goel, Ashish; Aggarwal, Praveen

2007-01-01

Acute poisoning with pesticides is a global public health problem and accounts for as many as 300,000 deaths worldwide every year. The majority of deaths occur due to exposure to organophosphates, organochlorines and aluminium phosphide. Organophosphate compounds inhibit acetylcholinesterase resulting in acute toxicity. Intermediate syndrome can develop in a number of patients and may lead to respiratory paralysis and death. Management consists of proper oxygenation, atropine in escalating doses and pralidoxime in high doses. It is Important to decontaminate the skin while taking precautions to avoid secondary contamination of health personnel. Organochlorine pesticides are toxic to the central nervous system and sensitize the myocardium to catecholamines. Treatment involves supportive care and avoiding exogenous sympathomimetic agents. Ingestion of paraquat causes severe inflammation of the throat, corrosive injury to the gastrointestinal tract, renal tubular necrosis, hepatic necrosis and pulmonary fibrosis. Administration of oxygen should be avoided as it produces more fibrosis. Use of immunosuppressive agents have improved outcome in patients with paraquat poisoning. Rodenticides include thallium, superwarfarins, barium carbonate and phosphides (aluminium and zinc phosphide). Alopecia is an atypical feature of thallium toxicity. Most exposures to superwarfarins are harmless but prolonged bleeding may occur. Barium carbonate Ingestion can cause severe hypokalaemia and respiratory muscle paralysis. Aluminium phosphide is a highly toxic agent with mortality ranging from 37% to 100%. It inhibits mitochondrial cytochrome c oxidase and leads to pulmonary and cardiac toxicity. Treatment is supportive with some studies suggesting a beneficial effect of magnesium sulphate. Pyrethroids and insect repellants (e.g. diethyltoluamide) are relatively harmless but can cause toxic effects to pulmonary and central nervous systems. Ethylene dibromide-a highly toxic, fumigant pesticide-produces oral ulcerations, followed by liver and renal toxicity, and is almost uniformly fatal. Physicians working in remote and rural areas need to be educated about early diagnosis and proper management using supportive care and antidotes, wherever available.

Phytoextraction of As and Fe using Hibiscus cannabinus L. from soil polluted with landfill leachate.

PubMed

Meera, M; Agamuthu, P

2012-02-01

Terrestrial plants as potential phytoremediators for remediation of surface soil contaminated with toxic metals have gained attention in clean-up technologies. The potential of kenaf (Hibiscus cannabinus L.) to offer a cost-effective mechanism to remediate Fe and As from landfill leachate-contaminated soil was investigated. Pot experiment employing soil polluted with treatments of Jeram landfill leachate was conducted for 120 days. Plants were harvested after 8th, 12th, and 16th weeks of growth. Accumulation of Fe and As was assessed based on Bioconcentration Factor and Translocation Factor. Results showed sequestration of 0.06-0.58 mg As and 66.82-461.71 mg Fe per g plant dry weight in kenaf root, which implies that kenaf root can be an bioavailable sink for toxic metals. Insignificant amount of Fe and As was observed in the aerial plant parts (< 12% of total bioavailable metals). The ability of kenaf to tolerate these metals and avoid phytotoxicity could be attributed to the stabilization of the metals in the roots and hence reduction of toxic metal mobility (TF < 1). With the application of leachate, kenaf was also found to have higher biomass and subsequently recorded 11% higher bioaccumulation capacity, indicating its suitability for phytoextraction of leachate contaminated sites.

Methods of Responsibly Managing End-of-Life Foams and Plastics Containing Flame Retardants: Part I.

PubMed

Lucas, Donald; Petty, Sara M; Keen, Olya; Luedeka, Bob; Schlummer, Martin; Weber, Roland; Barlaz, Morton; Yazdani, Ramin; Riise, Brian; Rhodes, James; Nightingale, Dave; Diamond, Miriam L; Vijgen, John; Lindeman, Avery; Blum, Arlene; Koshland, Catherine P

2018-06-01

Flame retardants (FRs) are added to foams and plastics to comply with flammability standards and test requirements in products for household and industrial uses. When these regulations were implemented, potential health and environmental impacts of FR use were not fully recognized or understood. Extensive research in the past decades reveal that exposure to halogenated FRs, such as those used widely in furniture foam, is associated with and/or causally related to numerous health effects in animals and humans. While many of the toxic FRs have been eliminated and replaced by other FRs, existing products containing toxic or potentially toxic chemical FRs will remain in use for decades, and new products containing these and similar chemicals will permeate the environment. When such products reach the end of their useful life, proper disposal methods are needed to avoid health and ecological risks. To minimize continued human and environmental exposures to hazardous FR chemicals from discarded products, waste management technologies and processes must be improved. This review discusses a wide range of issues associated with all aspects of the use and responsible disposal of wastes containing FRs, and identifies basic and applied research needs in the areas of responsible collection, pretreatment, processing, and management of these wastes.

Comparative evaluation of effects of ozonated and chlorinated thermal discharges on estuarine and fresh water organisms. First quarterly progress report, April 1979

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

Guerra, C.R.; DelMonaco, J.L.; Singletary, J.H.

1979-01-01

The biological evaluation program incorporates three types of experimental tests: acute (96 hour) toxicity studies; behavioral (avoidance) response studies; and physiological (cough) response studies. In addition, specimens used in testing are examined for physical damage resulting from exposure to chlorine or ozoen. The objective of the acute (96 hour) toxicity study is to determine the respective lethal levels (LC/sub 50/) of chlorinated and ozonated waters. The objective of the behavioral (avoidance) response study is to determine what (if any) concentrations of ozone and of chlorine will be avoided. The objective of physiological (cough) response study is to determine what concentrationsmore » of ozone and of chlorine are physiologically detected. Ozonated and chlorinated waters were evaluated in all studies for both the addition of increased temperature and without it. Results indicate that ozone is less toxic than chlorine under the test conditions used. The lethal levels vary according to species of water quality measurements at Bergen Generating Station, New York are tabulated. (JBG)« less

Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG)

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

Anker, Christopher J., E-mail: chris.anker@UVMHealth.org; Grossmann, Kenneth F.; Atkins, Michael B.

2016-06-01

BRAF kinase gene V600 point mutations drive approximately 40% to 50% of all melanomas, and BRAF inhibitors (BRAFi) have been found to significantly improve survival outcomes. Although radiation therapy (RT) provides effective symptom palliation, there is a lack of toxicity and efficacy data when RT is combined with BRAFi, including vemurafenib and dabrafenib. This literature review provides a detailed analysis of potential increased dermatologic, pulmonary, neurologic, hepatic, esophageal, and bowel toxicity from the combination of BRAFi and RT for melanoma patients described in 27 publications. Despite 7 publications noting potential intracranial neurotoxicity, the rates of radionecrosis and hemorrhage from wholemore » brain RT (WBRT), stereotactic radiosurgery (SRS), or both do not appear increased with concurrent or sequential administration of BRAFis. Almost all grade 3 dermatitis reactions occurred when RT and BRAFi were administered concurrently. Painful, disfiguring nondermatitis cutaneous reactions have been described from concurrent or sequential RT and BRAFi administration, which improved with topical steroids and time. Visceral toxicity has been reported with RT and BRAFi, with deaths possibly related to bowel perforation and liver hemorrhage. Increased severity of radiation pneumonitis with BRAFi is rare, but more concerning was a potentially related fatal pulmonary hemorrhage. Conversely, encouraging reports have described patients with leptomeningeal spread and unresectable lymphadenopathy rendered disease free from combined RT and BRAFi. Based on our review, the authors recommend holding RT ≥3 days before and after fractionated RT and ≥1 day before and after SRS. No fatal reactions have been described with a dose <4 Gy per fraction, and time off systemic treatment should be minimized. Future prospective data will serve to refine these recommendations.« less

Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG)

PubMed Central

Anker, Christopher J.; Grossmann, Kenneth F.; Atkins, Michael B.; Suneja, Gita; Tarhini, Ahmad A.; Kirkwood, John M.

2016-01-01

BRAF kinase gene V600 point mutations drive approximately 40% to 50% of all melanomas, and BRAF inhibitors (BRAFi) have been found to significantly improve survival outcomes. Although radiation therapy (RT) provides effective symptom palliation, there is a lack of toxicity and efficacy data when RT is combined with BRAFi, including vemurafenib and dabrafenib. This literature review provides a detailed analysis of potential increased dermatologic, pulmonary, neurologic, hepatic, esophageal, and bowel toxicity from the combination of BRAFi and RT for melanoma patients described in 27 publications. Despite 7 publications noting potential intracranial neurotoxicity, the rates of radionecrosis and hemorrhage from whole brain RT (WBRT), stereotactic radiosurgery (SRS), or both do not appear increased with concurrent or sequential administration of BRAFis. Almost all grade 3 dermatitis reactions occurred when RT and BRAFi were administered concurrently. Painful, disfiguring nondermatitis cutaneous reactions have been described from concurrent or sequential RT and BRAFi administration, which improved with topical steroids and time. Visceral toxicity has been reported with RT and BRAFi, with deaths possibly related to bowel perforation and liver hemorrhage. Increased severity of radiation pneumonitis with BRAFi is rare, but more concerning was a potentially related fatal pulmonary hemorrhage. Conversely, encouraging reports have described patients with leptomeningeal spread and unresectable lymphadenopathy rendered disease free from combined RT and BRAFi. Based on our review, the authors recommend holding BRAFi and/or MEK inhibitors ≥3 days before and after fractionated RT and ≥1 day before and after SRS. No fatal reactions have been described with a dose <4 Gy per fraction, and time off systemic treatment should be minimized. Future prospective data will serve to refine these recommendations. PMID:27131079

Potential primary and secondary hazards of avicides

USGS Publications Warehouse

Schafer, E.W.; Clark, Dell O.

1984-01-01

There are six chemicals or groups of chemicals that are currently registered as avicides that can be used in some or all of the U.S. Most of these chemicals, because of their diverse chemical composition and innate toxicological effects, present somewhat different primary and secondary hazards to avian and mammalian predators and scavengers. Of the chemicals reviewed, all appear to present some degree of primary hazard to non-target birds and mammals; however, PA-14, the Starlicide family of chemicals and fenthion appear to be the least hazardous when used according to use directions. 4-Aminopyridine, endrin and strychnine, because of their high acute toxicity and lack of selectivity, must be considered potentially more hazardous. With respect to secondary hazards, the ranking of chemicals changes considerably and only PA-14 appears to present a negligible hazard. The Starlicide family of chemicals presents negligible hazards to most animal species under currently registered uses, but may be potentially hazardous to cats and owls under specific use conditions. Two chemicals, 4-aminopyridine and strychnine, are potentially more hazardous to predatory and scavenger animals due to their highly toxic nature and rapid lethal effects in target species, leaving unassimilated chemical in the gastrointestinal tract. The remaining chemicals, endrin and fenthion, have been shown to possess the potential for more significant secondary poisoning; however, because of restrictive uses, most of the potential hazards have been avoided in operational use.

Characteristic Features and Contributory Factors in Fatal Ciguatera Fish Poisoning—Implications for Prevention and Public Education

PubMed Central

Chan, Thomas Y. K.

2016-01-01

In this review, the main objective was to describe the characteristic features of fatal ciguatera fish poisoning and identify contributory factors, with a view to promote prevention and public education. Ciguatera-related deaths, although rare, have been reported from the Pacific, Caribbean, and Indian Ocean regions. The clinical features were generally dominated by convulsions and coma, with various focal neurological signs. Several contributory factors could be identified, including consumption of ciguatoxin (CTX)-rich fish parts (viscera and head) in larger amounts, the most ciguatoxic fish species (e.g., Gymnothorax flavimarginatus) and reef fish collected after storms and individuals' susceptibility. Mass ciguatera fish poisoning with mortalities also occurred when G. flavimarginatus and other ciguatoxic fish species were shared in gatherings and parties. The characteristic features of fatal ciguatera fish poisoning must be recognized early. The public should be repeatedly reminded to avoid eating the most ciguatoxic fish species and the CTX-rich parts of reef fish. To prevent mass poisoning in gatherings and parties, the most ciguatoxic fish species and potentially toxic fish species must be avoided. Particularly after hits by disastrous storms, it is important to monitor the toxicity of reef fish and the incidence rates of ciguatera. PMID:26787145

Characteristic Features and Contributory Factors in Fatal Ciguatera Fish Poisoning--Implications for Prevention and Public Education.

PubMed

Chan, Thomas Y K

2016-04-01

In this review, the main objective was to describe the characteristic features of fatal ciguatera fish poisoning and identify contributory factors, with a view to promote prevention and public education. Ciguatera-related deaths, although rare, have been reported from the Pacific, Caribbean, and Indian Ocean regions. The clinical features were generally dominated by convulsions and coma, with various focal neurological signs. Several contributory factors could be identified, including consumption of ciguatoxin (CTX)-rich fish parts (viscera and head) in larger amounts, the most ciguatoxic fish species (e.g.,Gymnothorax flavimarginatus) and reef fish collected after storms and individuals' susceptibility. Mass ciguatera fish poisoning with mortalities also occurred when G. flavimarginatus and other ciguatoxic fish species were shared in gatherings and parties. The characteristic features of fatal ciguatera fish poisoning must be recognized early. The public should be repeatedly reminded to avoid eating the most ciguatoxic fish species and the CTX-rich parts of reef fish. To prevent mass poisoning in gatherings and parties, the most ciguatoxic fish species and potentially toxic fish species must be avoided. Particularly after hits by disastrous storms, it is important to monitor the toxicity of reef fish and the incidence rates of ciguatera. © The American Society of Tropical Medicine and Hygiene.

Ecotoxicological risks of the abandoned F-Ba-Pb-Zn mining area of Osor (Spain).

PubMed

Bori, Jaume; Vallès, Bettina; Navarro, Andrés; Riva, Maria Carme

2017-06-01

Due to its potential toxic properties, metal mobilization is of major concern in areas surrounding Pb-Zn mines. In the present study, metal contents and toxicity of soils, aqueous extracts from soils and mine drainage waters from an abandoned F-Ba-Pb-Zn mining area in Osor (Girona, NE Spain) were evaluated through chemical extractions and ecotoxicity bioassays. Toxicity assessment in the terrestrial compartment included lethal and sublethal endpoints on earthworms Eisenia fetida, arthropods Folsomia candida and several plant species, whereas aquatic tests involved bacteria Vibrio fischeri, microalgae Raphidocelis subcapitata and crustaceans Daphnia magna. Total concentrations of Ba (250-5110 mg kg -1 ), Pb (940 to >5000 mg kg -1 ) and Zn (2370-11,300 mg kg -1 ) in soils exceeded intervention values to protect human health. Risks for the aquatic compartment were identified in the release of drainage waters and in the potential leaching and runoff of metals from contaminated soils, with Cd (1.98-9.15 µg L -1 ), Pb (2.11-326 µg L -1 ) and Zn (280-2900 µg L -1 ) concentrations in filtered water samples surpassing US EPA Water Quality Criteria (2016a, b). Terrestrial ecotoxicity tests were in accordance with metal quantifications and identified the most polluted soil as the most toxic. Avoidance and reproduction tests with earthworms showed the highest sensitivity to metal contamination. Aquatic bioassays performed in aqueous extracts from soils confirmed the results from terrestrial tests and also detected toxic effects caused by the mine drainage waters. Algal growth inhibition was the most sensitive aquatic endpoint. In view of the results, the application of a containment or remediative procedure in the area is encouraged.

Bio-oil production of softwood and hardwood forest industry residues through fast and intermediate pyrolysis and its chromatographic characterization.

PubMed

Torri, Isadora Dalla Vecchia; Paasikallio, Ville; Faccini, Candice Schmitt; Huff, Rafael; Caramão, Elina Bastos; Sacon, Vera; Oasmaa, Anja; Zini, Claudia Alcaraz

2016-01-01

Bio-oils were produced through intermediate (IP) and fast pyrolysis (FP), using Eucalyptus sp. (hardwood) and Picea abies (softwood), wood wastes produced in large scale in Pulp and Paper industries. Characterization of these bio-oils was made using GC/qMS and GC×GC/TOFMS. The use of GC×GC provided a broader characterization of bio-oils and it allowed tracing potential markers of hardwood bio-oil, such as dimethoxy-phenols, which might co-elute in 1D-GC. Catalytic FP increased the percentage of aromatic hydrocarbons in P. abies bio-oil, indicating its potential for fuel production. However, the presence of polyaromatic hydrocarbons (PAH) draws attention to the need of a proper management of pyrolysis process in order to avoid the production of toxic compounds and also to the importance of GC×GC/TOFMS use to avoid co-elutions and consequent inaccuracies related to identification and quantification associated with GC/qMS. Ketones and phenols were the major bio-oil compounds and they might be applied to polymer production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toxicity of the ionophore antibiotic lasalocid to soil-dwelling invertebrates: avoidance tests in comparison to classic sublethal tests.

PubMed

Žižek, Suzana; Zidar, Primož

2013-07-01

Lasalocid is a veterinary ionophore antibiotic used for prevention and treatment of coccidiosis in poultry. It enters the environment with the use of contaminated manure on agricultural land. Despite its extensive use, the effects of lasalocid on non-target soil organisms are poorly explored. We used classical subleathal ecotoxicity tests to assess the effects of lasalocid on earthworms (Eisenia andrei) and isopods (Porcellio scaber) and compared the results with tests using avoidance behaviour as the endpoint. The results showed that avoidance is a much more sensitive endpoint. For earthworms, EC50 for avoidance (12.3 mg kg(-1) dry soil) was more than five times lower than EC50 for reproduction (69.6 mg kg(-1) dry soil). In isopods the sensitivity of the behavioural response test was even higher. While the highest lasalocid concentration 202 mg kg(-1) had no significant effects on isopod growth or survival, already the lowest used concentration in the behavioural assay (4.51 mg kg(-1)) caused significant impact on isopod behaviour. Using the avoidance test results for calculating the predicted no-effect concentration (PNEC) of lasalocid to soil invertebrates, the value is close to the predicted environmental concentration (PEC). This indicates that the use of lasalocid-contaminated manure could potentially impair the habitat function of agricultural soils. Copyright © 2013 Elsevier Ltd. All rights reserved.

Terpenoid constituents of cinnamon and clove essential oils cause toxic effects and behavior repellency response on granary weevil, Sitophilus granarius.

PubMed

Plata-Rueda, Angelica; Campos, Juliana Mendonça; da Silva Rolim, Gabriela; Martínez, Luis Carlos; Dos Santos, Marcelo Henrique; Fernandes, Flávio Lemes; Serrão, José Eduardo; Zanuncio, José Cola

2018-07-30

This study evaluated toxic effects, repellency and respiration rate caused by terpenoid constituents of cinnamon and clove essential oils and against Sitophilus granarius L. (Coleoptera: Curculionidae). The lethal concentrations (LC 50 and LC 90 ), repellent effect, and behavior repellency response on adults of S. granarius after exposure to six concentrations of each essential oil and terpenoids were evaluated. The chemical composition of the cinnamon oil was also determined and primary compounds were eugenol (10.5%), trans-3-caren-2-ol (10.2%), benzyl benzoate (9.99%), caryophyllene (9.34%), eugenyl acetate (7.71%), α-phellandrene (7.41%), and α-pinene (7.14%). In clove essential oil, the primary compounds were eugenol (27.1%), caryophyllene (24.5%), caryophyllene oxide (18.3%), 2-propenoic acid (12.2%), α-humulene (10.8%), γ-cadinene (5.01%), and humulene oxide (4.84%). Cinnamon and clove essential oil was toxic to S. granarius. In toxic terpenoids compounds, eugenol has stronger contact toxicity in S. granarius than caryophyllene oxide, followed by α-pinene, α-humulene, and α-phellandrene. Insects reduced their respiratory rates after being exposed to essential oil terpenoids and avoided or reduced their mobility on terpenoid-treated surfaces. Cinnamon and clove essential oil, and their terpenoid constituents were toxic and repellent to adult S. granarius and, therefore, have the potential to prevent or retard the development of insecticide resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

PubMed Central

Dubińska-Magiera, Magda; Daczewska, Małgorzata; Lewicka, Anna; Migocka-Patrzałek, Marta; Niedbalska-Tarnowska, Joanna; Jagla, Krzysztof

2016-01-01

The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio) has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans. PMID:27869769

e-Biologics: Fabrication of Sustainable Electronics with "Green" Biological Materials.

PubMed

Lovley, Derek R

2017-06-27

The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial components as the guide for synthesis, are a potential green solution. Some e-biologics can be fabricated from renewable feedstocks with relatively low energy inputs, often while avoiding the harsh chemicals used for synthesizing more traditional electronic materials. Several are completely free of toxic components, can be readily recycled, and offer unique features not found in traditional electronic materials in terms of size, performance, and opportunities for diverse functionalization. An appropriate investment in the concerted multidisciplinary collaborative research required to identify and characterize e-biologics and to engineer materials and devices based on e-biologics could be rewarded with a new "green age" of sustainable electronic materials and devices. Copyright © 2017 Lovley.

Insecticidal Properties of Essential Oils and Some of Their Constituents on the Turkestan Cockroach (Blattodea: Blattidae).

PubMed

Gaire, Sudip; O'Connell, Mary; Holguin, Francisco O; Amatya, Anup; Bundy, Scott; Romero, Alvaro

2017-04-01

The Turkestan cockroach, Blatta lateralis (Walker), has become the most important peridomestic species in urban areas of the Southwestern United States. The aim of this study was to evaluate the use of botanical compounds to control this urban pest. We tested the acute toxicity and repellency of six botanical constituents and three essential oils on Turkestan cockroach nymphs. Chemical composition of the essential oils was also determined. Topical and fumigant assays with nymphs showed that thymol was the most toxic essential oil constituent, with a LD50 of 0.34 mg/nymph and a LC50 of 27.6 mg/liter air, respectively. Contact toxicity was also observed in assays with trans-Cinnamaldehyde, eugenol, geraniol, methyl eugenol, and p-Cymene. Methyl eugenol and geraniol had limited fumigant toxicity. The essential oils from red thyme, clove bud, and Java citronella exhibited toxicity against nymphs. Cockroaches avoided fresh dry residues of thymol and essential oils. Chemical analysis of the essential oils confirmed high contents of effective essential oil constituents. Our results demonstrated that essential oils and some of their constituents have potential as eco-friendly insecticides for the management of Turkestan cockroaches. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Predictors of Rectal Tolerance Observed in a Dose-Escalated Phase 1-2 Trial of Stereotactic Body Radiation Therapy for Prostate Cancer

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

Kim, D.W. Nathan; Cho, L. Chinsoo; Straka, Christopher

2014-07-01

Purpose: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. Methods and Materials: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. Results: At the highest dose level, 6.6% ofmore » patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm{sup 3} (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). Conclusion: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.« less

Therapeutic Properties and Biological Benefits of Marine-Derived Anticancer Peptides

PubMed Central

Kang, Hee Kyoung; Choi, Moon-Chang; Seo, Chang Ho; Park, Yoonkyung

2018-01-01

Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells through different mechanisms, such as apoptosis, disruption of the tubulin-microtubule balance, and inhibition of angiogenesis. Traditional chemotherapeutic agents have side effects and depress immune responses. Thus, the research and development of novel anticancer peptides with low toxicity to normal human cells and mechanisms of action capable of avoiding multi-drug resistance may provide a new method for anticancer treatment. This review provides useful information on the potential of marine anticancer peptides for human therapy. PMID:29558431

Parrots eat nutritious foods despite toxins.

PubMed

Gilardi, James D; Toft, Catherine A

2012-01-01

Generalist herbivores are challenged not only by the low nitrogen and high indigestibility of their plant foods, but also by physical and chemical defenses of plants. This study investigated the foods of wild parrots in the Peruvian Amazon and asked whether these foods contain dietary components that are limiting for generalist herbivores (protein, lipids, minerals) and in what quantity; whether parrots chose foods based on nutrient content; and whether parrots avoid plants that are chemically defended. We made 224 field observations of free-ranging parrots of 17 species in 8 genera foraging on 102 species of trees in an undisturbed tropical rainforest, in two dry seasons (July-August 1992-1993) and one wet season (January-February1994). We performed laboratory analyses of parts of plants eaten and not eaten by parrots and brine shrimp assays of toxicity as a proxy for vertebrates. Parrots ate seeds, fruits, flowers, leaves, bark, and insect larvae, but up to 70% of their diet comprised seeds of many species of tropical trees, in various stages of ripeness. Plant parts eaten by parrots were rich in protein, lipid, and essential minerals, as well as potentially toxic chemicals. Seeds were higher than other plant materials in protein and lipid and lower in fiber. Large macaws of three species ate foods higher in protein and lipids and lower in fiber compared to plant parts available but not eaten. Macaws ate foods that were lower in phenolic compounds than foods they avoided. Nevertheless, foods eaten by macaws contained measurable levels of toxicity. Macaws did not appear to make dietary selections based on mineral content. Parrots represent a remarkable example of a generalist herbivore that consumes seeds destructively despite plant chemical defenses. With the ability to eat toxic foods, rainforest-dwelling parrots exploited a diversity of nutritious foods, even in the dry season when food was scarce for other frugivores and granivores.

Parrots Eat Nutritious Foods despite Toxins

PubMed Central

Gilardi, James D.

2012-01-01

Background Generalist herbivores are challenged not only by the low nitrogen and high indigestibility of their plant foods, but also by physical and chemical defenses of plants. This study investigated the foods of wild parrots in the Peruvian Amazon and asked whether these foods contain dietary components that are limiting for generalist herbivores (protein, lipids, minerals) and in what quantity; whether parrots chose foods based on nutrient content; and whether parrots avoid plants that are chemically defended. Methodology/Principal Findings We made 224 field observations of free-ranging parrots of 17 species in 8 genera foraging on 102 species of trees in an undisturbed tropical rainforest, in two dry seasons (July-August 1992–1993) and one wet season (January-February1994). We performed laboratory analyses of parts of plants eaten and not eaten by parrots and brine shrimp assays of toxicity as a proxy for vertebrates. Parrots ate seeds, fruits, flowers, leaves, bark, and insect larvae, but up to 70% of their diet comprised seeds of many species of tropical trees, in various stages of ripeness. Plant parts eaten by parrots were rich in protein, lipid, and essential minerals, as well as potentially toxic chemicals. Seeds were higher than other plant materials in protein and lipid and lower in fiber. Large macaws of three species ate foods higher in protein and lipids and lower in fiber compared to plant parts available but not eaten. Macaws ate foods that were lower in phenolic compounds than foods they avoided. Nevertheless, foods eaten by macaws contained measurable levels of toxicity. Macaws did not appear to make dietary selections based on mineral content. Conclusions/Significance Parrots represent a remarkable example of a generalist herbivore that consumes seeds destructively despite plant chemical defenses. With the ability to eat toxic foods, rainforest-dwelling parrots exploited a diversity of nutritious foods, even in the dry season when food was scarce for other frugivores and granivores. PMID:22679496

Avoidance behavior of ruffe exposed to selected formulations of piscicides

USGS Publications Warehouse

Dawson, Verdel K.; Bills, Terry D.; Boogaard, Michael A.

1998-01-01

Ruffe were introduced into Duluth Harbor, Minnesota in the early 1980s, probably by release of ballast water from sea-going freighters. Since then, it has become the most abundant species in the fish community. The sensitivity of ruffe to a number of piscicides has been demonstrated, however, the feasibility of using piscicides to control populations depends on whether ruffe cart detect piscicides and move to untreated water, We used a two-choice preference resting system to evaluate avoidance or attraction reactions of ruffe during exposures to the lampricides TFM and bayluscide and the general fish toxicants rotenone and antimycin. We used a second testing system to evaluate the potential for benthic ruffe to move vertically in the water column to avoid piscicides dissolving from experimental bottom-release formulations of bayluscide and antimycin. Near-lethal concentrations of TFM and rotenone tended to repel ruffe. Antimycin and bayluscide did not seem to repel ruffe in the avoidance chamber, but bottom-release formulations (antimycin granules-0.25% a.i. And bayluscide granules-3.2% a.i.) did cause increased swimming and surfacing activity among ruffe in column tests. We conclude that TFM and rotenone could be used to trent entire bodies of water, while bottom-release formulations of antimycin and bayluscide may have more application for treating localized concentrations of ruffe.

Human health tradeoffs in wellhead drinking water treatment: Comparing exposure reduction to embedded life cycle risks.

PubMed

Gifford, Mac; Chester, Mikhail; Hristovski, Kiril; Westerhoff, Paul

2018-01-01

Treatment of drinking water decreases human health risks by reducing pollutants, but the required materials, chemicals, and energy emit pollutants and increase health risks. We explored human carcinogenic and non-carcinogenic disease tradeoffs of water treatment by comparing pollutant dose-response curves against life cycle burden using USEtox methodology. An illustrative wellhead sorbent groundwater treatment system removing hexavalent chromium or pentavalent arsenic serving 3200 people was studied. Reducing pollutant concentrations in drinking water from 20 μg L -1 to 10 μg L -1 avoided 37 potential cancer cases and 64 potential non-cancer disease cases. Human carcinogenicity embedded in treatment was 0.2-5.3 cases, and non-carcinogenic toxicity was 0.2-14.3 cases, depending on technology and degree of treatment. Embedded toxicity impacts from treating Cr(VI) using strong-base anion exchange were <10% of those from using weak base anion exchange. Acidification and neutralization contributed >90% of the toxicity impacts for treatment options requiring pH control. In scenarios where benefits exceeded burdens, tradeoffs still existed. Benefits are experienced by a local population but burdens are born externally where the materials and energy are produced, thus exporting the health risks. Even when burdens clearly exceeded benefits, cost considerations may still drive selecting a detrimental treatment level or technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

The first toxicological study of the antiozonant and research tool ethylene diurea (EDU) using a Lemna minor L. bioassay: Hints to its mode of action.

PubMed

Agathokleous, Eugenios; Mouzaki-Paxinou, Akrivi-Chara; Saitanis, Costas J; Paoletti, Elena; Manning, William J

2016-06-01

The antiozonant and research tool ethylene diurea (EDU) is widely studied as a phytoprotectant against the widespread pollutant ground-surface ozone. Although it has been extensively used, its potential toxicity in the absence of ozone is unknown and its mode of action is unclear. The purpose of this research was to toxicologically assess EDU and to further investigate its mode of action using Lemna minor L. as a model organism. Application of EDU concentrations greater than 593 mg L(-1) (practically 600 mg L(-1)) resulted in adverse inhibition of colony growth. As no-observed-toxic-effects concentration (NOEL) we recommend a concentration of 296 mg L(-1) (practically 300 mg L(-1)). A hormetic response was detected, i.e. stimulatory effects of low EDU concentrations, which may indicate overcompensation in response to disruption in homeostasis. Growth inhibition and suppressed biomass were associated with impacted chlorophyll a fluorescence (ΦPSII, qP and ETR). Furthermore, EDU increased mesophyll thickness, as indicated by frond succulence index. Applications of concentrations ≥593 mg L(-1) to uncontrolled environments should be avoided due to potential toxicity to sensitive organisms and the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Responses of Earthworm to Aluminum Toxicity in Latosol

Treesearch

Jia-En Zhang; Jiayu Yu; Ying Ouyang; Huaqin Xu

2012-01-01

Excess aluminum (Al) in soils due to acid rain leaching is toxic to water resources and harmful to soil organisms and plants. This study investigated adverse impacts of Al levels upon earthworms (Eisenia fetida) from the latosol (acidic red soil). Laboratory experiments were performed to examine the survival and avoidance of earthworms from high Al...

Avoidance behaviour of Enchytraeus albidus: effects of benomyl, carbendazim, phenmedipham and different soil types.

PubMed

Amorim, Mónica J B; Römbke, Jörg; Soares, Amadeu M V M

2005-04-01

Enchytraeids are typical inhabitants of many soils, contributing to vital processes of this environmental compartment. Indirectly they are involved in regulating the degradation of organic matter, as well as improving the pore structure of the soil. Due to their behaviour, they are able to avoid unfavourable environmental conditions. Avoidance tests with enchytraeids, initially developed with earthworms by several authors, are quick and easy to perform. With these tests a first assessment of the toxicity of a (contaminated or spiked) soil is possible in just 48 h by using the reaction of the enchytraeids as measurement endpoint. In this period of time the organisms can choose between the control soil and the other soil (a contaminated or spiked or another soil with different physico-chemical properties). In the tests reported here, the enchytraeids were exposed to control soils spiked with the fungicides Benomyl and Carbendazim and the herbicide Phenmedipham. Several chemical concentrations were tested in order to evaluate the avoidance behaviour to toxic substances. In fact, often these short-term screening tests gave results showing avoidance at concentrations in a range similar to the acute test results but, higher than in chronic tests. Further tests are needed to decide whether the results gained in this study can be extrapolated to other chemicals. It is proposed to standardize the Enchytraeid Avoidance Test as it is currently done for the Earthworm Avoidance Test by the International Standard Organization (ISO).

Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

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

Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.

1995-11-01

The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding studymore » with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.« less

Proposed modification to avoidance test with Eisenia fetida to assess metal toxicity in agricultural soils affected by mining activities.

PubMed

Delgadillo, Víctor; Verdejo, José; Mondaca, Pedro; Verdugo, Gabriela; Gaete, Hernán; Hodson, Mark E; Neaman, Alexander

2017-06-01

Use of avoidance tests is a quick and cost-effective method of assessing contaminants in soils. One option for assessing earthworm avoidance behavior is a two-section test, which consists of earthworms being given the choice to move between a test soil and a control substrate. For ecological relevance, tested soils should be field-contaminated soils. For practical reasons, artificial soils are commonly used as the control substrate. Interpretation of the test results compromised when the test soil and the artificial substrate differ in their physico-chemical properties other than just contaminants. In this study we identified the physico-chemical properties that influence avoidance response and evaluated the usefulness of adjusting these in the control substrate in order to isolate metal-driven avoidance of field soils by earthworms. A standardized two-section avoidance test with Eisenia fetida was performed on 52 uncontaminated and contaminated (Cu >155mgkg -1 , As >19mgkg -1 ) agricultural soils from the Aconcagua River basin and the Puchuncaví Valley in Chile. Regression analysis indicated that the avoidance response was determined by soil organic matter (OM), electrical conductivity (EC) and total soil Cu. Organic matter content of the artificial substrate was altered by peat additions and EC by NaCl so that these properties matched those of the field soils. The resultant EC 80 for avoidance (indicative of soils of "limited habitat") was 433mg Cu kg -1 (339 - 528mgkg -1 95% confidence intervals). The earthworm avoidance test can be used to assess metal toxicity in field-contaminated soils by adjusting physico-chemical properties (OM and EC) of the artificial control substrate in order to mimic those of the field-collected soil. Copyright © 2017 Elsevier Inc. All rights reserved.

Thinking outside the liver: Induced pluripotent stem cells for hepatic applications

PubMed Central

Subba Rao, Mekala; Sasikala, Mitnala; Reddy, D Nageshwar

2013-01-01

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications. PMID:23801830

Thinking outside the liver: induced pluripotent stem cells for hepatic applications.

PubMed

Subba Rao, Mekala; Sasikala, Mitnala; Nageshwar Reddy, D

2013-06-14

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.

Toxicity of thermal degradation products of spacecraft materials

NASA Technical Reports Server (NTRS)

Lawrence, W. H.; Turner, J. E.; Sanford, C.; Foster, S.; Baldwin, E.; Oconnor, J.

1982-01-01

Three polymeric materials were evaluated for relative toxicity of their pyrolysis products to rats by inhalation: Y-7683 (LS 200), Y-7684 (Vonar 3 on Fiberglass), and Y-7685 (Vonar 3 on N W Polyester). Criteria employed for assessing relative toxicity were (1) lethality from in-chamber pyrolysis, (2) lethality from an outside-of-chamber pyrolysis MSTL Procedure, and (3) disruption of trained rats' shock-avoidance performance during sub-lethal exposures to in-chamber pyrolysis of the materials.

An alternative approach to combination vaccines: intradermal administration of isolated components for control of anthrax, botulism, plague and staphylococcal toxic shock

PubMed Central

Morefield, Garry L; Tammariello, Ralph F; Purcell, Bret K; Worsham, Patricia L; Chapman, Jennifer; Smith, Leonard A; Alarcon, Jason B; Mikszta, John A; Ulrich, Robert G

2008-01-01

Background Combination vaccines reduce the total number of injections required for each component administered separately and generally provide the same level of disease protection. Yet, physical, chemical, and biological interactions between vaccine components are often detrimental to vaccine safety or efficacy. Methods As a possible alternative to combination vaccines, we used specially designed microneedles to inject rhesus macaques with four separate recombinant protein vaccines for anthrax, botulism, plague and staphylococcal toxic shock next to each other just below the surface of the skin, thus avoiding potentially incompatible vaccine mixtures. Results The intradermally-administered vaccines retained potent antibody responses and were well- tolerated by rhesus macaques. Based on tracking of the adjuvant, the vaccines were transported from the dermis to draining lymph nodes by antigen-presenting cells. Vaccinated primates were completely protected from an otherwise lethal aerosol challenge by Bacillus anthracis spores, botulinum neurotoxin A, or staphylococcal enterotoxin B. Conclusion Our results demonstrated that the physical separation of vaccines both in the syringe and at the site of administration did not adversely affect the biological activity of each component. The vaccination method we describe may be scalable to include a greater number of antigens, while avoiding the physical and chemical incompatibilities encountered by combining multiple vaccines together in one product. PMID:18768085

Highly sensitive avoidance plays a key role in sensory adaptation to deep-sea hydrothermal vent environments.

PubMed

Ogino, Tetsuya; Maegawa, Shingo; Shigeno, Shuichi; Fujikura, Katsunori; Toyohara, Haruhiko

2018-01-01

The environments around deep-sea hydrothermal vents are very harsh conditions for organisms due to the possibility of exposure to highly toxic compounds and extremely hot venting there. Despite such extreme environments, some indigenous species have thrived there. Alvinellid worms (Annelida) are among the organisms best adapted to high-temperature and oxidatively stressful venting regions. Although intensive studies of the adaptation of these worms to the environments of hydrothermal vents have been made, little is known about the worms' sensory adaptation to the severe chemical conditions there. To examine the sensitivity of the vent-endemic worm Paralvinella hessleri to low pH and oxidative stress, we determined the concentration of acetic acid and hydrogen peroxide that induced avoidance behavior of this worm, and compared these concentrations to those obtained for related species inhabiting intertidal zones, Thelepus sp. The concentrations of the chemicals that induced avoidance behavior of P. hessleri were 10-100 times lower than those for Thelepus sp. To identify the receptors for these chemicals, chemical avoidance tests were performed with the addition of ruthenium red, a blocker of transient receptor potential (TRP) channels. This treatment suppressed the chemical avoidance behavior of P. hessleri, which suggests that TRP channels are involved in the chemical avoidance behavior of this species. Our results revealed for the first time hypersensitive detection systems for acid and for oxidative stress in the vent-endemic worm P. hessleri, possibly mediated by TRP channels, suggesting that such sensory systems may have facilitated the adaptation of this organism to harsh vent environments.

Earthworms lost from pesticides application in potato crops

NASA Astrophysics Data System (ADS)

Garcia-Santos, Glenda; Forrer, Karin; Binder, Claudia R.

2010-05-01

Bioturbation from earthworm's activity contributes to soil creep and soil carbon dynamics, and provide enough aeration conditions for agricultural practices all over the world. In developing countries where there is a long term misuse of pesticides for agricultural purposes, lost of these benefits from earthworms activity might already yielded negative effects in the current crop production. Little research has been performed on earthworms avoidance to pesticides in developing countries located in the tropics. Furthermore, the complete avoidance reaction (from attraction to 100% avoidance) from earthworms to most of the pesticides used in potato cultivation in developing countries like Colombia is incomplete as yet. Hence the aim of this study is to assess the lost of earthworm on the soils caused by different concentrations of pesticides and associated agricultural impacts caused by a lost in the soil bioturbation. As a first stage, we have studied earthworm's avoidance to pesticide concentration in a potato agricultural area located in Colombia. Local cultivated Eisenia fetida were exposed to four of the most frequent applied active ingredients in potato crops i.e. carbofuran, mancozeb, methamidophos and chlorpyriphos. Adult earthworm toxicity experiments were carried out in two soils, untreated grasslands under standard (ISO guidelines) and undisturbed conditions, and exposed to six different concentrations of the active ingredients. The results of the avoidance reaction on the standard soils were significant for carbofuran, mancoceb and chlorpyrifos. For each of the three active ingredients, we found i) overuse of pesticide, ii) applied dose of carbofuran, mancoceb and chlorpyrifos by the farmers potentially caused 20%, 11% and 9% of earthworms avoidance on the cultivated soils, respectively.

The consequences of lifetime and evolutionary exposure to toxic prey: changes in avoidance behaviour through ontogeny.

PubMed

Robbins, T R; Langkilde, T

2012-10-01

Responses to novel threats (e.g. invasive species) can involve genetic changes or plastic shifts in phenotype. There is controversy over the relative importance of these processes for species survival of such perturbations, but we are realizing they are not mutually exclusive. Native eastern fence lizards (Sceloporus undulatus) have adapted to top-down predation pressure imposed by the invasive red imported fire ant (Solenopsis invicta) via changes in adult (but not juvenile) lizard antipredator behaviour. Here, we examine the largely ignored, but potentially equally important, bottom-up effect of fire ants as toxic prey for lizards. We test how fire ant consumption (or avoidance) is affected by lifetime (via plasticity) and evolutionary (via natural selection) exposure to fire ants by comparing field-caught and laboratory-reared lizards, respectively, from fire ant-invaded and uninvaded populations. More naive juveniles from invaded populations ate fire ants than did adults, reflecting a natural ontogenetic dietary shift away from ants. Laboratory-reared lizards from the invaded site were less likely to eat fire ants than were those from the uninvaded site, suggesting a potential evolutionary shift in feeding behaviour. Lifetime and evolutionary exposure interacted across ontogeny, however, and field-caught lizards from the invaded site exhibited opposite ontogenetic trends; adults were more likely to eat fire ants than were juveniles. Our results suggest that plastic and evolutionary processes may both play important roles in permitting species survival of novel threats. We further reveal how complex interactions can shape adaptive responses to multimodal impacts imposed by invaders: in our system, fire ants impose stronger bottom-up selection than top-down selection, with each selection regime changing differently across lizard ontogeny. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Evolutionary Responses to Invasion: Cane Toad Sympatric Fish Show Enhanced Avoidance Learning

PubMed Central

Caller, Georgina; Brown, Culum

2013-01-01

The introduced cane toad (Bufo marinus) poses a major threat to biodiversity due to its lifelong toxicity. Several terrestrial native Australian vertebrates are adapting to the cane toad’s presence and lab trials have demonstrated that repeated exposure to B. marinus can result in learnt avoidance behaviour. Here we investigated whether aversion learning is occurring in aquatic ecosystems by comparing cane toad naïve and sympatric populations of crimson spotted rainbow fish (Melanotaenia duboulayi). The first experiment indicated that fish from the sympatric population had pre-existing aversion to attacking cane toad tadpoles but also showed reduced attacks on native tadpoles. The second experiment revealed that fish from both naïve and sympatric populations learned to avoid cane toad tadpoles following repeated, direct exposure. Allopatric fish also developed a general aversion to tadpoles. The aversion learning abilities of both groups was examined using an experiment involving novel distasteful prey items. While both populations developed a general avoidance of edible pellets in the presence of distasteful pellets, only the sympatric population significantly reduced the number of attacks on the novel distasteful prey item. These results indicate that experience with toxic prey items over multiple generations can enhance avoidance leaning capabilities via natural selection. PMID:23372788

Larkspur (Delphinium spp.) poisoning in livestock.

PubMed

Pfister, J A; Gardner, D R; Panter, K E; Manners, G D; Ralphs, M H; Stegelmeier, B L; Schoch, T K

1999-02-01

Larkspurs (Delphinium spp.) are toxic plants that contain numerous diterpenoid alkaloids which occur as one of two structural types: (1) lycotonine, and (2) 7,8-methylenedioxylycoctonine (MDL-type). Among the lycoctonine type alkaloids are three N-(methylsuccinimido) anthranoyllycoctonine (MSAL-type) alkaloids which appear to be most toxic: methyllycaconitine (MLA), 14-deacetylnudicauline (DAN), and nudicauline. An ester function at C-18 is an important structural requirement for toxicity. Intoxication results from neuromuscular paralysis, as nicotinic acetylcholine receptors in the muscle and brain are blocked by toxic alkaloids. Clinical signs include labored breathing, rapid and irregular heartbeat, muscular weakness, and collapse. Toxic alkaloid concentration generally declines in tall larkspurs with maturation, but alkaloid concentration varies over years and from plant to plant, and is of little use for predicting consumption by cattle. Knowledge of toxic alkaloid concentration is valuable for management purposes when cattle begin to eat larkspur. Cattle generally begin consuming tall larkspur after flowering racemes are elongated, and consumption increases as larkspur matures. Weather is also a major factor in cattle consumption, as cattle tend to eat more larkspur during or just after summer storms. Management options that may be useful for livestock producers include conditioning cattle to avoid larkspur (food aversion learning), grazing tall larkspur ranges before flowering (early grazing) and after seed shatter (late grazing), grazing sheep before cattle, herbicidal control of larkspur plants, and drug therapy for intoxicated animals. Some potentially fruitful research avenues include examining alkaloid chemistry in low and plains larkspurs, developing immunologic methods for analyzing larkspur alkaloids, developing drug therapy, and devising grazing regimes specifically for low and plains larkspur.

[Safety evaluation and risk control measures of Cassiae Semen].

PubMed

Zhao, Yi-Meng; Wu, Li; Zhang, Shuo; Zhang, Li; Gao, Xue-Min; Sun, Xiao-Bo; Wang, Chun

2017-11-01

In this study, the authors reviewed domestic and foreign literatures, conducted the textual research on origin and development of Cassia Semen, studied records in ancient books and ancient and modern literatures, clinical adverse reactions and relevant experimental studies in recent years, and summarized the clinical features and influencing factors related to the safety of Cassiae Semen. According to the findings,Cassia Semen's safety risks are mainly liver and kidney system damages, with the main clinical features of fatigue, anorexia, disgusting of oil, yellow urine and gray stool; digestive system injury, with the main clinical features of diarrhea, abdominal distension, nausea and loose stool; reproductive system damage, with the main clinical features of vaginal bleeding. Allergic reactions and clinical adverse events, with the main clinical features for numb mouth, itching skin, nausea and vomiting, diarrhea, wheezing and lip cyanosis were also reported. The toxicological studies on toxic components of Cassiae Semen obtusifolia were carried out through acute toxicity test, subacute toxicity test, subchronic toxicity test and chronic toxicity test. Risk factors might include patients, compatibility and physicians. Physicians should strictly abide by the medication requirements in the Pharmacopoeia, pay attention to rational compatibility, appropriate dosage,correct usage and appropriate processing, control the dosage below 15 g to avoid excessive intake, strictly control the course of treatment to avoid accumulated poisoning caused by long-term administration. At the same time, clinicians should pay attention to the latest research progress, update the knowledge structure, quickly find the latest and useful materials from clinical practice, scientific research and drug information and other literatures, make evaluation and judgment for the materials, establish a traditional Chinese medicine intelligence information library, and strengthen the control over adverse effects with a pre-warning consciousness. The authors suggested standardizing clinical medication of Cassiae Semen, and avoiding misuse or excessive use; clinicians should prescribe it in strict accordance with there commended usage and dosage in the Pharmacopoeia, and focus on the safety signal accumulation in clinic, while strengthening studies for toxic substance basis and toxicity mechanism, in order to give full play to Cassiae Semen's clinical efficacy and reduce its adverse reactions. Copyright© by the Chinese Pharmaceutical Association.

Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy.

PubMed

Lee, Tsair-Fwu; Liou, Ming-Hsiang; Ting, Hui-Min; Chang, Liyun; Lee, Hsiao-Yi; Wan Leung, Stephen; Huang, Chih-Jen; Chao, Pei-Ju

2015-08-20

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration.

Ozone Contamination in Aircraft Cabins. Appendix B: Overview papers. Flight 8 planning to avoid high ozone

NASA Technical Reports Server (NTRS)

Belmont, A. D.

1979-01-01

The problem of preventing cabin ozone from exceeding a given standard was investigated. Statistical analysis of vertical distribution of ozone is summarized. The cost, logistics, maintenance, ability to forecast ozone, and avoiding high ozone concentrations are presented. Filtering approaches and the requirements to remove ozone toxicity are discussed.

Proactive aquatic ecotoxicological assessment of room-temperature ionic liquids

USGS Publications Warehouse

Kulacki, K.J.; Chaloner, D.T.; Larson, J.H.; Costello, D.M.; Evans-White, M. A.; Docherty, K.M.; Bernot, R.J.; Brueseke, M.A.; Kulpa, C.F.; Lamberti, G.A.

2011-01-01

Aquatic environments are being contaminated with a myriad of anthropogenic chemicals, a problem likely to continue due to both unintentional and intentional releases. To protect valuable natural resources, novel chemicals should be shown to be environmentally safe prior to use and potential release into the environment. Such proactive assessment is currently being applied to room-temperature ionic liquids (ILs). Because most ILs are water-soluble, their effects are likely to manifest in aquatic ecosystems. Information on the impacts of ILs on numerous aquatic organisms, focused primarily on acute LC50 and EC50 endpoints, is now available, and trends in toxicity are emerging. Cation structure tends to influence IL toxicity more so than anion structure, and within a cation class, the length of alkyl chain substituents is positively correlated with toxicity. While the effects of ILs on several aquatic organisms have been studied, the challenge for aquatic toxicology is now to predict the effects of ILs in complex natural environments that often include diverse mixtures of organisms, abiotic conditions, and additional stressors. To make robust predictions about ILs will require coupling of ecologically realistic laboratory and field experiments with standard toxicity bioassays and models. Such assessments would likely discourage the development of especially toxic ILs while shifting focus to those that are more environmentally benign. Understanding the broader ecological effects of emerging chemicals, incorporating that information into predictive models, and conveying the conclusions to those who develop, regulate, and use those chemicals, should help avoid future environmental degradation. ?? 2011 Bentham Science Publishers Ltd.

Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics

PubMed Central

Jończyk-Matysiak, Ewa; Weber-Dąbrowska, Beata; Owczarek, Barbara; Międzybrodzki, Ryszard; Łusiak-Szelachowska, Marzanna; Łodej, Norbert; Górski, Andrzej

2017-01-01

Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes—contained in granules—that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy. The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy. PMID:28613272

Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics.

PubMed

Jończyk-Matysiak, Ewa; Weber-Dąbrowska, Beata; Owczarek, Barbara; Międzybrodzki, Ryszard; Łusiak-Szelachowska, Marzanna; Łodej, Norbert; Górski, Andrzej

2017-06-14

Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes-contained in granules-that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy . The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy.

Rheological alteration of erythrocytes exposed to carbon nanotubes.

PubMed

Heo, Yujin; Li, Cheng-Ai; Kim, Duckjong; Shin, Sehyun

2017-01-01

Single-walled carbon nanotubes (SWNTs) have been increasingly used in a variety of biomedical applications, such as in vivo delivery of drugs and tumor imaging. Potential exposure of SWNTs to human red blood cells (RBCs) may cause serious toxicity including alteration of mechanical properties of cells. The present study investigated the cellular response to exposure of SWNTs with measuring rheological characteristics of RBCs, including hemolysis, deformability, aggregation, and morphological changes. RBCs were exposed to two different dispersion-state samples (i.e. individual SWNTs and bundled SWNTs) in chitosan hydroxyphenyl acetamide (CHPA) solutions. The concentrations of SWNTs were carefully chosen to avoid any hemorheological alterations due to hemolysis. Rheological characteristics were measured using microfluidic-laser diffractometry and aggregometry. Our results show that the bundled SWNTs had higher hemolytic activity than did the individual SWNTs. RBC aggregation apparently decreased as the concentration of SWNTs or incubation time increased. Additionally, bundled SWNTs caused significant alterations in the shape and fusion of RBCs. In conclusion, bundled SWNTs were found to be more toxic than individual SWNTs. These results provide important insights into the interactions between RBCs and SWNTs and will facilitate assessment of the risk of nanomaterial toxicity of blood.

Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects

PubMed Central

Patterson, Stephen; Wyllie, Susan

2014-01-01

There is an urgent need for new, safer, and effective treatments for the diseases caused by the protozoan parasites Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. In the search for more effective drugs to treat these ‘neglected diseases’ researchers have chosen to reassess the therapeutic value of nitroaromatic compounds. Previously avoided in drug discovery programs owing to potential toxicity issues, a nitro drug is now being used successfully as part of a combination therapy for human African trypanosomiasis. We describe here the rehabilitation of nitro drugs for the treatment of trypanosomatid diseases and discuss the future prospects for this compound class. PMID:24776300

[Not Available].

PubMed

Charbonneau, Annie

2013-07-01

Methylene blue is used in medical practice for various reasons. Recent findings point to a potential interaction with serotonin reuptake inhibitors (SRIs) that could lead to serotonergic toxicity. To describe the risk of serotonergic toxicity associated with the interaction between methylene blue and SRIs. Relevant publications were searched systematically via MEDLINE (1946 to March 21, 2013) and Embase (1974 to 2013, week 11) with the following search terms: "methylene blue", "methylthioninium", "monoamine oxidase inhibitors", "serotonin reup-take inhibitors", and "serotonin syndrome". No restrictions were applied in relation to the indication for methylene blue or the language of publication. The reference lists of identified articles were also searched. Eighteen case reports and 2 case series were identified for inclusion. To date, no randomized controlled trials have been published. The first case report indicating suspicion of an interaction between methylene blue and SRIs was published in 2003. Seventeen other case reports describing the same type of interaction have been published since then. The 2 case series provided data from about 325 parathyroidectomies in which methylene blue was used for staining. The 17 patients who experienced central nervous system toxicity were all taking SRIs in the preoperative period. When administered in combination with SRIs, methylene blue may lead to serotonergic toxicity at doses as low as 0.7 mg/kg. Methylene blue would seem to have monoamine oxidase A inhibitory properties. Precautions should be taken to avoid this interaction. [Publisher's translation].

Evaluation of the safety of ancient strains of wheat in coeliac disease reveals heterogeneous small intestinal T cell responses suggestive of coeliac toxicity.

PubMed

Šuligoj, Tanja; Gregorini, Armando; Colomba, Mariastella; Ellis, H Julia; Ciclitira, Paul J

2013-12-01

Coeliac disease is a chronic small intestinal immune-mediated enteropathy triggered by dietary gluten in genetically predisposed individuals. Since it is unknown if all wheat varieties are equally toxic to coeliac patients seven Triticum accessions showing different origin (ancient/modern) and ploidy (di-, tetra- hexaploid) were studied. Selected strains of wheat were ancient Triticum monococcum precoce (AA genome) and Triticum speltoides (BB genome), accessions of Triticum turgidum durum (AABB genome) including two ancient (Graziella Ra and Kamut) and two modern (Senatore Cappelli and Svevo) durum strains of wheat and Triticum aestivum compactum (AABBDD genome). Small intestinal gluten-specific T-cell lines generated from 13 coeliac patients were tested with wheat accessions by proliferation assays. All strains of wheat independent of ploidy or ancient/modern origin triggered heterogeneous responses covering wide ranges of stimulation indices. Ancient strains of wheat, although previously suggested to be low or devoid of coeliac toxicity, should be tested for immunogenicity using gluten-specific T-cell lines from multiple coeliac patients rather than gluten-specific clones to assess their potential toxicity. Our findings provide further evidence for the need for a strict gluten-free diet in coeliac patients, including avoidance of ancient strains of wheat. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Diet composition exacerbates or attenuates soman toxicity in rats: implied metabolic control of nerve agent toxicity.

PubMed

Myers, Todd M; Langston, Jeffrey L

2011-06-01

To evaluate the role of diet composition on nerve agent toxicity, rats were fed four distinct diets ad libitum for 28 d prior to challenge with 110 μg/kg (1.0 LD(50), sc) soman. The four diets used were a standard rodent diet, a choline-enriched diet, a glucose-enriched diet, and a ketogenic diet. Body weight was recorded throughout the study. Toxic signs and survival were evaluated at key times for up to 72 h following soman exposure. Additionally, acquisition of discriminated shuttlebox avoidance performance was characterized beginning 24h after soman challenge and across the next 8 d (six behavioral sessions). Prior to exposure, body weight was highest in the standard diet group and lowest in the ketogenic diet group. Upon exposure, differences in soman toxicity as a function of diet became apparent within the first hour, with mortality in the glucose-enriched diet group reaching 80% and exceeding all other groups (in which mortality ranged from 0 to 6%). At 72 h after exposure, mortality was 100% in the glucose-enriched diet group, and survival approximated 50% in the standard and choline-enriched diet groups, but equaled 87% in the ketogenic diet group. Body weight loss was significantly reduced in the ketogenic and choline-enriched diet groups, relative to the standard diet group. At 1 and 4h after exposure, rats in the ketogenic diet group had significantly lower toxic sign scores than all other groups. The ketogenic diet group performed significantly better than the standard diet group on two measures of active avoidance performance. The exacerbated soman toxicity observed in the glucose-enriched diet group coupled with the attenuated soman toxicity observed in the ketogenic diet group implicates glucose availability in the toxic effects of soman. This increased glucose availability may enhance acetylcholine synthesis and/or utilization, thereby exacerbating peripheral and central soman toxicity. Published by Elsevier B.V.

LCA of management strategies for RDF incineration and gasification bottom ash based on experimental leaching data.

PubMed

Di Gianfilippo, Martina; Costa, Giulia; Pantini, Sara; Allegrini, Elisa; Lombardi, Francesco; Astrup, Thomas Fruergaard

2016-01-01

The main characteristics and environmental properties of the bottom ash (BA) generated from thermal treatment of waste may vary significantly depending on the type of waste and thermal technology employed. Thus, to ensure that the strategies selected for the management of these residues do not cause adverse environmental impacts, the specific properties of BA, in particular its leaching behavior, should be taken into account. This study focuses on the evaluation of potential environmental impacts associated with two different management options for BA from thermal treatment of Refuse Derived Fuel (RDF): landfilling and recycling as a filler for road sub bases. Two types of thermal treatment were considered: incineration and gasification. Potential environmental impacts were evaluated by life-cycle assessment (LCA) using the EASETECH model. Both non-toxicity related impact categories (i.e. global warming and mineral abiotic resource depletion) and toxic impact categories (i.e. human toxicity and ecotoxicity) were assessed. The system boundaries included BA transport from the incineration/gasification plants to the landfills and road construction sites, leaching of potentially toxic metals from the BA, the avoided extraction, crushing, transport and leaching of virgin raw materials for the road scenarios, and material and energy consumption for the construction of the landfills. To provide a quantitative assessment of the leaching properties of the two types of BA, experimental leaching data were used to estimate the potential release from each of the two types of residues. Specific attention was placed on the sensitivity of leaching properties and the determination of emissions by leaching, including: leaching data selection, material properties and assumptions related to emission modeling. The LCA results showed that for both types of BA, landfilling was associated with the highest environmental impacts in the non-toxicity related categories. For the toxicity related categories, the two types of residues behaved differently. For incineration BA the contribution of metal leaching to the total impacts had a dominant role, with the highest environmental loads resulting for the road scenario. For the gasification BA, the opposite result was obtained, due to the lower release of contaminants observed for this material compared to incineration BA. Based on the results of this study, it may be concluded that, depending on the type of BA considered, its leaching behavior may significantly affect the results of a LCA regarding its management strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Behavioral technology and its application to fire toxicology research

NASA Technical Reports Server (NTRS)

Russo, D. M.

1978-01-01

The application of behavioral technology to the toxicity testing of pyrolysis/combustion (P/C) products is discussed and two categories of behavioral tests commonly employed in fire toxicology programs are reviewed. Data are presented from a comparison of carbon monoxide (CO) induced incapacitation in rats performing in a rotating wheel or under a Sidmon free-operant schedule of shock avoidance. Rats performing in the rotating wheel were behaviorally incapacitated at CO concentrations and carboxyhemoglobin levels significantly lower than those which incapacitated operant avoidance animals. It is concluded that different measures of behavioral incapacitation may vary since incapacitation is a function of the particular toxic mechanism at work and the behavioral requirements of the specific task employed in the test procedure.

e-Biologics: Fabrication of Sustainable Electronics with “Green” Biological Materials

PubMed Central

2017-01-01

ABSTRACT The growing ubiquity of electronic devices is increasingly consuming substantial energy and rare resources for materials fabrication, as well as creating expansive volumes of toxic waste. This is not sustainable. Electronic biological materials (e-biologics) that are produced with microbes, or designed with microbial components as the guide for synthesis, are a potential green solution. Some e-biologics can be fabricated from renewable feedstocks with relatively low energy inputs, often while avoiding the harsh chemicals used for synthesizing more traditional electronic materials. Several are completely free of toxic components, can be readily recycled, and offer unique features not found in traditional electronic materials in terms of size, performance, and opportunities for diverse functionalization. An appropriate investment in the concerted multidisciplinary collaborative research required to identify and characterize e-biologics and to engineer materials and devices based on e-biologics could be rewarded with a new “green age” of sustainable electronic materials and devices. PMID:28655820

Immunotherapy for bladder cancer

PubMed Central

Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James SA

2015-01-01

It is nearly 40 years since Bacillus Calmette–Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy

PubMed Central

Lee, Tsair-Fwu; Liou, Ming-Hsiang; Ting, Hui-Min; Chang, Liyun; Lee, Hsiao-Yi; Wan Leung, Stephen; Huang, Chih-Jen; Chao, Pei-Ju

2015-01-01

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration. PMID:26289304

Effects of a fire-retardant chemical to fathead minnows in experimental streams

USGS Publications Warehouse

Calfee, R.D.; Little, E.E.

2003-01-01

Background. Each year millions of liters of fire-retardant chemicals are applied to wildfires across the nation. Recent laboratory studies with long-term fire-retardant chemicals indicate a significant photoenhanced toxicity of products containing sodium ferrocyanide corrosion inhibitors. Our objective of this study was to determine the toxicity of fire-retardant chemicals to fathead minnows during exposure in experimental outdoor streams. Methods. Stream tests were conducted to determine the potential toxicity of a pulse of exposure as might occur when fire retardant chemical is rinsed from the watershed by rainfall. Two artificial 55-meter experimental streams were dosed with different concentrations of Fire-Trol?? GTS-R, or uncontaminated for a control. Replicate groups of fathead minnows were added to screened containers (10 fish per container) and exposed to retardant chemicals in the recirculating flow of the stream for up to 6 hours. Results and Discussion. Under field conditions toxicity of GTS-R only occurred in the presence of sunlight. When GTS-R was tested on sunny days, 100% mortality occurred. However, when tested during heavily overcast conditions, no mortality occurred. Conclusions. Lethal concentrations of cyanide were measured when GTS-R with YPS exposures were conducted under sunny conditions, but not under cloudy conditions, indicating that a minimum UV level is necessary to induce toxicity as well as the release of cyanide from YPS. The toxicity observed with GTS-R was likely associated with lethal concentrations of cyanide. Rainwater runoff following applications of this fire-retardant at the recommended rate could result in lethal concentrations in small ponds and streams receiving limited water flow under sunny conditions. Recommendations and Outlook. In addition to avoiding application to aquatic habitats, it is important to consider characteristics of the treated site including soil binding affinity and erosive properties.

Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

PubMed

Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

2016-10-01

Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations. Copyright © 2016 Elsevier Inc. All rights reserved.

The phytoremediation potential of native plants on New Zealand dairy farms.

PubMed

Hahner, Jason L; Robinson, Brett H; Hong-Tao, Zhong; Dickinson, Nicholas M

2014-01-01

Ecological restoration of marginal land and riparian zones in agricultural landscapes in New Zealand enhances the provision of above-ground ecosystem services. We investigated whether native endemic plant assemblages have remediation potential, through modifying soil nutrient and trace element mobility. Analysis of native plant foliage in situ indicated that selective uptake of a range of commonly deficient trace elements including Zn, B, Cu, Mn and Co could provide a browse crop to avoid deficiencies of these elements in livestock, although some native plants may enhance the risk of Mo and Cd toxicity. Native plant rhizospheres were found to modify soil physico-chemistry and are likely to influence lateral and vertical fluxes of chemical elements in drainage waters. Native plants on marginal land in agricultural landscapes could add value to dairy production systems whilst helping to resolve topical environmental issues.

An empirical study of the toxic capsule crisis in China: risk perceptions and behavioral responses.

PubMed

Feng, Tianjun; Keller, L Robin; Wu, Ping; Xu, Yifan

2014-04-01

The outbreak of the toxic capsule crisis during April 2012 aroused widespread public concern about the risk of chromium-contaminated capsules and drug safety in China. In this article, we develop a conceptual model to investigate risk perceptions of the pharmaceutical drug capsules and behavioral responses to the toxic capsule crisis and the relationship between associated factors and these two variables. An online survey was conducted to test the model, including questions on the measures of perceived efficacy of the countermeasures, trust in the State FDA (Food and Drug Administration), trust in the pharmaceutical companies, trust in the pharmaceutical capsule producers, risk perception, concern, need for information, information seeking, and risk avoidance. In general, participants reported higher levels of risk perception, concern, and risk avoidance, and lower levels of trust in the three different stakeholders. The results from the structural equation modeling procedure suggest that perceived efficacy of the countermeasures is a predictor of each of the three trust variables; however, only trust in the State FDA has a dampening impact on risk perception. Both risk perception and information seeking are significant determinants of risk avoidance. Risk perception is also positively related to concern. Information seeking is positively related to both concern and need for information. The theoretical and policy implications are also discussed. © 2013 Society for Risk Analysis.

Cardiac Amyloidosis

MedlinePlus

... adding salt to food, and avoiding eating in restaurants. Daily weighing can be helpful: a weight gain ... effective but toxic therapy, and very careful patient selection is needed. View this table: View inline View ...

Phenocopy of warfarin syndrome in an infant born to a mother with sickle cell anemia and severe transfusional iron overload.

PubMed

Xie, Yi; Pivnick, Eniko K; Cohen, Harris L; Adams-Graves, Patricia E; Pourcyrous, Massroor; Aygun, Banu; Hankins, Jane S

2013-08-01

Neonatal chondrodysplasia punctata (CDP) is characterized by epiphyseal stippling and midfacial hypoplasia. CDP is usually inherited, but can be acquired because of maternal vitamin K deficiency. We describe an infant with CDP born to a teenager with sickle cell anemia and transfusional iron overload. The mother had severe liver fibrosis, elevated liver iron concentration (34 mg Fe/g), and coagulopathy, but no gestational use of warfarin. Fetal abnormalities were attributed to vitamin K deficiency secondary to liver dysfunction from iron toxicity. Treatment of iron overload among women with sickle cell anemia of childbearing potential is important to avoid possible CDP in newborns.

Estrogen-induced myelotoxicity in dogs: A review

PubMed Central

Sontas, Hasan B.; Dokuzeylu, Banu; Turna, Ozge; Ekici, Hayri

2009-01-01

Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone marrow toxicity in dogs. The condition is characterized by hematologic abnormalities including thrombocytopenia, anemia, and leukocytosis or leukopenia. Despite intensive therapy with blood or platelet-rich transfusions, broad-spectrum antibiotics, steroids, and bone marrow stimulants, prognosis is unfavorable. Due to the the risk of stimulating the development of uterine diseases and the potential for inducing aplastic anemia, estrogen use in dogs is best avoided where possible. This paper describes the causes of estrogen-induced myelotoxicity, the clinical presentation of the patients, the diagnosis, and the treatment options in the dog. PMID:20046604

Recurrent Streptococcus agalactiae Toxic Shock Syndrome Triggered by a Tumor Necrosis Factor-α Inhibitor

PubMed Central

Yoshida, Masataka; Takazono, Takahiro; Tashiro, Masato; Saijo, Tomomi; Morinaga, Yoshitomo; Yamamoto, Kazuko; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Sawai, Toyomitsu; Nishino, Tomoya; Izumikawa, Koichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

2016-01-01

Streptococcal toxic shock syndrome caused by group B streptococcus (GBS) is a rare, but lethal disease. We experienced a 45-year-old woman with pustular psoriasis who developed toxic shock-like syndrome during infliximab treatment. Surprisingly, similar episodes recurred three times in one year with restarting of infliximab treatments. In the third episode, GBS were detected in blood, urine, and vaginal secretion cultures. These episodes of shock syndrome were possibly due to GBS. To the best of our knowledge, this is the first case report of recurrent streptococcal toxic shock syndrome possibly caused by GBS which was induced by anti-TNF-α inhibitor therapy. The restarting of biological agents in patients with a history of toxic shock syndrome should therefore be avoided as much as possible. PMID:27803422

Recurrent Streptococcus agalactiae Toxic Shock Syndrome Triggered by a Tumor Necrosis Factor-α Inhibitor.

PubMed

Yoshida, Masataka; Takazono, Takahiro; Tashiro, Masato; Saijo, Tomomi; Morinaga, Yoshitomo; Yamamoto, Kazuko; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Sawai, Toyomitsu; Nishino, Tomoya; Izumikawa, Koichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

Streptococcal toxic shock syndrome caused by group B streptococcus (GBS) is a rare, but lethal disease. We experienced a 45-year-old woman with pustular psoriasis who developed toxic shock-like syndrome during infliximab treatment. Surprisingly, similar episodes recurred three times in one year with restarting of infliximab treatments. In the third episode, GBS were detected in blood, urine, and vaginal secretion cultures. These episodes of shock syndrome were possibly due to GBS. To the best of our knowledge, this is the first case report of recurrent streptococcal toxic shock syndrome possibly caused by GBS which was induced by anti-TNF-α inhibitor therapy. The restarting of biological agents in patients with a history of toxic shock syndrome should therefore be avoided as much as possible.

In Vitro Exposures in Diesel Exhaust Atmospheres: Resuspension of PM from Filters Verses Direct Deposition of PM from Air

PubMed Central

Lichtveld, Kim M.; Ebersviller, Seth M.; Sexton, Kenneth G.; Vizuete, William; Jaspers, Ilona; Jeffries, Harvey E.

2012-01-01

One of the most widely used in vitro particulate matter (PM) exposures methods is the collection of PM on filters, followed by resuspension in a liquid medium, with subsequent addition onto a cell culture. To avoid disruption of equilibria between gases and PM, we have developed a direct in vitro sampling and exposure method (DSEM) capable of PM-only exposures. We hypothesize that the separation of phases and post-treatment of filter-collected PM significantly modifies the toxicity of the PM compared to direct deposition, resulting in a distorted view of the potential PM health effects. Controlled test environments were created in a chamber that combined diesel exhaust with an urban-like mixture. The complex mixture was analyzed using both the DSEM and concurrently-collected filter samples. The DSEM showed that PM from test atmospheres produced significant inflammatory response, while the resuspension exposures at the same exposure concentration did not. Increasing the concentration of resuspended PM sixteen times was required to yield measurable IL-8 expression. Chemical analysis of the resuspended PM indicated a total absence of carbonyl compounds compared to the test atmosphere during the direct-exposures. Therefore, collection and resuspension of PM into liquid modifies its toxicity and likely leads to underestimating toxicity. PMID:22834915

Combination of biochar amendment and mycoremediation for polycyclic aromatic hydrocarbons immobilization and biodegradation in creosote-contaminated soil.

PubMed

García-Delgado, Carlos; Alfaro-Barta, Irene; Eymar, Enrique

2015-03-21

Soils impregnated with creosote contain high concentrations of polycyclic aromatic hydrocarbons (PAH). To bioremediate these soils and avoid PAH spread, different bioremediation strategies were tested, based on natural attenuation, biochar application, wheat straw biostimulation, Pleurotus ostreatus mycoremediation, and the novel sequential application of biochar for 21 days and P. ostreatus 21 days more. Soil was sampled after 21 and 42 days after the remediation application. The efficiency and effectiveness of each remediation treatment were assessed according to PAH degradation and immobilization, fungal and bacterial development, soil eco-toxicity and legal considerations. Natural attenuation and biochar treatments did not achieve adequate PAH removal and soil eco-toxicity reduction. Biostimulation showed the highest bacterial development but low PAH degradation rate. Mycoremediation achieved the best PAH degradation rate and the lowest bioavailable fraction and soil eco-toxicity. This bioremediation strategy achieved PAH concentrations below Spanish legislation for contaminated soils (RD 9/2005). Sequential application of biochar and P. ostreatus was the second treatment most effective for PAH biodegradation and immobilization. However, the activity of P. ostreatus was increased by previous biochar application and PAH degradation efficiency was increased. Therefore, the combined strategy for PAH degradation have high potential to increase remediation efficiency. Copyright © 2014 Elsevier B.V. All rights reserved.

Combinations of chlorocatechols and heavy metals cause DNA degradation in vitro but must not result in increased mutation rates in vivo.

PubMed

Schweigert, N; Belkin, S; Leong-Morgenthaler, P; Zehnder, A J; Eggen, R I

1999-01-01

Chlorocatechols introduced into the environment directly or as a result of degradation processes are highly toxic, particularly when combined with heavy metals. With in vitro DNA degradation assays, the high reactivity of chlorocatechols combined with heavy metals could be shown, whereby copper was shown to be more active than iron. Structure-activity analysis showed that the degradation potential of the chlorocatechols decreased with an increasing number of chloratoms. The addition of reactive oxygen species scavengers allowed the identification of hydrogen peroxide as an important agent leading to DNA damage in this reaction. The potential of other reactive compounds, however, can neither be determined nor excluded with this approach. Exposure of Escherichia coli and Salmonella typhimurium cultures to the same mixtures of chlorocatechols and copper surprisingly did not lead to an enhanced mutation rate. This phenomenon was explained by doing marker gene expression measurements and toxicity tests with E. coli mutants deficient in oxidative stress defense or DNA repair. In catechol-copper-exposed cultures an increased peroxide level could indeed be demonstrated, but the highly efficient defense and repair systems of E. coli avoid the phenotypical establishment of mutations. Increased mutation rates under chronic exposure, however, cannot be excluded.

A novel bio-safe phase separation process for preparing open-pore biodegradable polycaprolactone microparticles.

PubMed

Salerno, Aurelio; Domingo, Concepción

2014-09-01

Open-pore biodegradable microparticles are object of considerable interest for biomedical applications, particularly as cell and drug delivery carriers in tissue engineering and health care treatments. Furthermore, the engineering of microparticles with well definite size distribution and pore architecture by bio-safe fabrication routes is crucial to avoid the use of toxic compounds potentially harmful to cells and biological tissues. To achieve this important issue, in the present study a straightforward and bio-safe approach for fabricating porous biodegradable microparticles with controlled morphological and structural features down to the nanometer scale is developed. In particular, ethyl lactate is used as a non-toxic solvent for polycaprolactone particles fabrication via a thermal induced phase separation technique. The used approach allows achieving open-pore particles with mean particle size in the 150-250 μm range and a 3.5-7.9 m(2)/g specific surface area. Finally, the combination of thermal induced phase separation and porogen leaching techniques is employed for the first time to obtain multi-scaled porous microparticles with large external and internal pore sizes and potential improved characteristics for cell culture and tissue engineering. Samples were characterized to assess their thermal properties, morphology and crystalline structure features and textural properties. Copyright © 2014 Elsevier B.V. All rights reserved.

50 CFR 600.510 - Gear avoidance and disposal.

Code of Federal Regulations, 2011 CFR

2011-10-01

... any marine resource, including marine mammals and birds, except in cases of emergency involving the..., fishing gear, net scraps, bale straps, plastic bags, oil drums, petroleum containers, oil, toxic chemicals...

Health impacts of domestic coal use in China

USGS Publications Warehouse

Finkelman, R.B.; Belkin, H.E.; Zheng, B.

1999-01-01

Domestic coal combustion has had profound adverse effects on the health of millions of people worldwide. In China alone several hundred million people commonly burn raw coal in unvented stoves that permeate their homes with high levels of toxic metals and organic compounds. At least 3,000 people in Guizhou Province in southwest China are suffering from severe arsenic poisoning. The primary source of the arsenic appears to be consumption of chili peppers dried over fires fueled with high-arsenic coal. Coal samples in the region were found to contain up to 35,000 ppm arsenic. Chili peppers dried over high-arsenic coal fires adsorb 500 ppm arsenic on average. More than 10 million people in Guizhou Province and surrounding areas suffer from dental and skeletal fluorosis. The excess fluorine is caused by eating corn dried over burning briquettes made from high-fluorine coals and high-fluorine clay binders. Polycyclic aromatic hydrocarbons formed during coal combustion are believed to cause or contribute to the high incidence of esophageal and lung cancers in parts of China. Domestic coal combustion also has caused selenium poisoning and possibly mercury poisoning. Better knowledge of coal quality parameters may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals and macerals in coal may help predict the behavior of the potentially toxic components during coal combustion.

Health impacts of domestic coal use in China

PubMed Central

Finkelman, Robert B.; Belkin, Harvey E.; Zheng, Baoshan

1999-01-01

Domestic coal combustion has had profound adverse effects on the health of millions of people worldwide. In China alone several hundred million people commonly burn raw coal in unvented stoves that permeate their homes with high levels of toxic metals and organic compounds. At least 3,000 people in Guizhou Province in southwest China are suffering from severe arsenic poisoning. The primary source of the arsenic appears to be consumption of chili peppers dried over fires fueled with high-arsenic coal. Coal samples in the region were found to contain up to 35,000 ppm arsenic. Chili peppers dried over high-arsenic coal fires adsorb 500 ppm arsenic on average. More than 10 million people in Guizhou Province and surrounding areas suffer from dental and skeletal fluorosis. The excess fluorine is caused by eating corn dried over burning briquettes made from high-fluorine coals and high-fluorine clay binders. Polycyclic aromatic hydrocarbons formed during coal combustion are believed to cause or contribute to the high incidence of esophageal and lung cancers in parts of China. Domestic coal combustion also has caused selenium poisoning and possibly mercury poisoning. Better knowledge of coal quality parameters may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals and macerals in coal may help predict the behavior of the potentially toxic components during coal combustion. PMID:10097053

Seed chemistry of Sophora chrysophylla (mamane) in relation to diet of specialist avian seed predator Loxioides bailleui (palila) in Hawaii

USGS Publications Warehouse

Banko, P.C.; Cipollini, M.L.; Breton, G.W.; Paulk, E.; Wink, M.; Izhaki, Ido

2002-01-01

This study describes the chemical ecology of a tritrophic interaction among species endemic to the island of Hawaii, USA: a tree (Sophora chrysophylla: mamane), an endangered bird (Loxioides bailleui; palila), and moth larvae (Cydia spp.). Palila and Cydia both specialize on the seed embryos of mamane but avoid eating the seed coats. Palila actively seek out and feed mamane embryos and Cydia larvae to their nestlings. Because mamane embryos contain potentially toxic levels of alkaloids, including broadly toxic quinolizidine alkaloids, and because insects often sequester alkaloids from their food plants, we focus on the questions of why palila forage upon mamane embryos and why they supplement their diet with Cydia larvae. Our data show that mamane embryos contain high amounts of potentially toxic alkaloids, but are well balanced nutritionally and contain lipids, carbohydrates, proteins, amino acids, and minerals at levels that are likely to be sufficient for maintenance and breeding. Mamane seed coats contain lower levels of alkaloids and nutrients, somewhat higher levels of phenolics, and much higher levels of nondigestible fiber. Taken together, these results suggest that palila have evolved tolerance to high levels of alkaloids and that they forage upon embryos primarily because of their availability in the habitat and high nutritional reward. Our data also suggest that Cydia are used by palila because they are readily accessible, nontoxic, and nutritious; the larvae apparently do not sequester alkaloids while feeding upon mamane seeds. Our results are interpreted with respect to the likelihood of current and historical coadaptive responses in this ecologically isolated and simplified island setting.

Comparative assessment of button cells using a normalized index for potential pollution by heavy metals.

PubMed

Moreno-Merino, Luis; Jiménez-Hernández, Maria Emilia; de la Losa, Almudena; Huerta-Muñoz, Virginia

2015-09-01

Many household batteries worldwide still end up in landfills or are incinerated due to inefficient collection and recycling schemes. Toxic heavy metals from improperly discarded button cells pose a serious risk to human health and the environment, as they can pollute air, soil and water. This paper analyses a series of button cells selected from batteries available on the retail market, and compares their polluting potential. A total of 64 batteries were subjected to chemical analyses of 19 elements - including metals and metalloids - , and energy density measurements. The samples were from four different brands of each of the four most common button cell technologies (alkaline, zinc-air, silver oxide and lithium). An energy-normalized index - the Weighted Potential Pollution Index (WPPI) - was proposed to compare the polluting potential of the different batteries. The higher the battery WPPI score, the greater the content in toxic elements and the lower the energy output. The results of the chemical composition and energy density varied depending on the construction technology of the button cells. However, significant differences in both variables were also found when comparing different brands within the same technology. The differences in WPPI values confirmed the existence of a significant margin to reduce the environmental impact of discarded button cells simply by avoiding the most polluting options. The choice of the battery with the most favourable WPPI produced a reduction in potential pollution of 3-53% for silver oxide batteries, 4-39% for alkaline, 20-28% for zinc-air and 12-26% for lithium. Comparative potential pollution could be assessed when selecting batteries using an energy-normalized index such as WPPI to reduce the environmental impact of improperly disposed button cells. Published by Elsevier B.V.

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

PubMed

Aguirrebengoa, Koldo

2014-11-01

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

Clinical consequences of toxic envenomations by Hymenoptera.

PubMed

Schmidt, Justin O

2018-05-19

Many familiar Hymenoptera are brightly colored and can sting painfully-thus, their threat and clinical importance may be exaggerated. Most stinging insects only sting to defend themselves or their colonies from predators. The clinical nature of Hymenoptera envenomations contrasts that of other venomous animals, including other arthropods, primarily because allergic reaction, not direct intoxication, is the usual main concern. This review focuses mainly on the clinical features of direct toxicity to Hymenoptera envenomations, which can induce a high incidence of acute renal failure, liver failure, multiple organ failures, and death. Toxic mass envenomations by honeybees usually entail many hundreds or more stings per victim. In contrast to honeybee toxic envenomations, hornet sting envenomations can be clinically threatening with only 20-200 stings needed to cause kidney and other organ failures. Many lethal envenomations by honeybees occur in rural areas in the New World and Africa and are not recorded or documented. In contrast, deaths by hornets occur mainly to Asia. The most frequent and important envenomating taxa are honeybees, hornets, yellowjacket wasps, paper wasps, fire ants, and jack jumper ants. Occasional envenomating taxa include bumblebees, bullet ants, harvester ants, solitary wasps, solitary bees, and various ants of lesser clinical importance. Envenomations by Hymenoptera usually can be avoided if one considers that bees, wasps and ants "view" us as potential threats or predators, and that with information about the biology of stinging Hymenoptera, humans can minimize adverse incidents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design of a high-throughput human neural crest cell migration assay to indicate potential developmental toxicants.

PubMed

Nyffeler, Johanna; Karreman, Christiaan; Leisner, Heidrun; Kim, Yong Jun; Lee, Gabsang; Waldmann, Tanja; Leist, Marcel

2017-01-01

Migration of neural crest cells (NCCs) is one of the pivotal processes of human fetal development. Malformations arise if NCC migration and differentiation are impaired genetically or by toxicants. In the currently available test systems for migration inhibition of NCC (MINC), the manual generation of a cell-free space results in extreme operator dependencies, and limits throughput. Here a new test format was established. The assay avoids scratching by plating cells around a commercially available circular stopper. Removal of the stopper barrier after cell attachment initiates migration. This microwell-based circular migration zone NCC function assay (cMINC) was further optimized for toxicological testing of human pluripotent stem cell (hPSC)-derived NCCs. The challenge of obtaining data on viability and migration by automated image processing was addressed by developing a freeware. Data on cell proliferation were obtained by labelling replicating cells, and by careful assessment of cell viability for each experimental sample. The role of cell proliferation as an experimental confounder was tested experimentally by performing the cMINC in the presence of the proliferation-inhibiting drug cytosine arabinoside (AraC), and by a careful evaluation of mitotic events over time. Data from these studies led to an adaptation of the test protocol, so that toxicant exposure was limited to 24 h. Under these conditions, a prediction model was developed that allows classification of toxicants as either inactive, leading to unspecific cytotoxicity, or specifically inhibiting NC migration at non-cytotoxic concentrations.

Irresistible ants: exposure to novel toxic prey increases consumption over multiple temporal scales.

PubMed

Herr, Mark W; Robbins, Travis R; Centi, Alan; Thawley, Christopher J; Langkilde, Tracy

2016-07-01

As species become increasingly exposed to novel challenges, it is critical to understand how evolutionary (i.e., generational) and plastic (i.e., within lifetime) responses work together to determine a species' fate or predict its distribution. The introduction of non-native species imposes novel pressures on the native species that they encounter. Understanding how native species exposed to toxic or distasteful invaders change their feeding behavior can provide insight into their ability to cope with these novel threats as well as broader questions about the evolution of this behavior. We demonstrated that native eastern fence lizards do not avoid consuming invasive fire ants following repeated exposure to this toxic prey. Rather fence lizards increased their consumption of these ants following exposure on three different temporal scales. Lizards ate more fire ants when they were exposed to this toxic prey over successive days. Lizards consumed more fire ants if they had been exposed to fire ants as juveniles 6 months earlier. Finally, lizards from populations exposed to fire ants over multiple generations consumed more fire ants than those from fire ant-free areas. These results suggest that the potentially lethal consumption of fire ants may carry benefits resulting in selection for this behavior, and learning that persists long after initial exposure. Future research on the response of native predators to venomous prey over multiple temporal scales will be valuable in determining the long-term effects of invasion by these novel threats.

Removal of toxic metals from leachates from hazardous solid wastes and reduction of toxicity to microtox by the use of calcium alginate beads containing humic acid.

PubMed

Pandey, Ashok K; Pandey, Shri Dhar; Misra, Virendra

2002-06-01

Improper disposal of hazardous wastes can lead to release of potentially harmful substances through leaching such as heavy metals, which ultimately contaminate soil, sediment surface water, and groundwater through runoff. To remove these toxic metals and avoid any adverse effect on the ecosystem, a novel approach involving calcium alginate (CA) beads containing humic acid (HA) was used. For this, 10% leachates of the waste obtained from two major industrial units with electroplating processess were prepared at neutral pH and analyzed by atomic absorption spectrophotometry (AAS). Both leachates contained Cd, Cu, Cr, Ni, Mn, Fe, and Zn. The concentrations of Ni, Mn, Fe, and Zn in the waste were found to be significant. The leachates analyzed were passed through columns packed with calcium alginate beads with or without humic acid. The concentrations of various metals in beads and in different fractions collected after adsorption were measured. Data recorded indicate that calcium alginate beads containing humic acids are more efficient in removal of all metals in substantial amounts from the two leachates. Along with removal of metals, this process led to considerable detoxification of the leachates as tested by Microtox assay, indicated by earlier protection and higher EC(50). The significance of the results in relation to removal of toxic metals by beads containing humic acid is discussed. (c) 2002 Elsevier Science (USA).

Feeding inhibition in Corbicula fluminea (O.F. Muller, 1774) as an effect criterion to pollutant exposure: Perspectives for ecotoxicity screening and refinement of chemical control.

PubMed

Castro, Bruno Branco; Silva, Carlos; Macário, Inês Patrunilho Efe; Oliveira, Bruno; Gonçalves, Fernando; Pereira, Joana Luísa

2018-03-01

Bivalves are commonly used in biomonitoring programs to track pollutants. Several features, including its filter-feeding abilities, cumulatively argue in favour of the use of the Asian clam (Corbicula fluminea) as a biosentinel and an ecotoxicological model. Filtration in bivalves is very sensitive to external stimuli and its control is dictated by regulation of the opening/closure of the valves, which may be used as an avoidance defence against contaminants. Here, we investigate the filter-feeding behaviour of the Asian clam as an endpoint for assessing exposure to pollutants, driven by two complementary goals: (i) to generate relevant and sensitive toxicological information based on the ability of C. fluminea to clear an algal suspension, using the invasive species as a surrogate for native bivalves; (ii) to gain insight on the potential of exploring this integrative response in the refinement of chemical control methods for this pest. Clearance rates and proportion of algae removed were measured using a simple and reproducible protocol. Despite some variation across individuals and size classes, 50-90% of food particles were generally removed within 60-120 min by clams larger than 20 mm. Removal of algae was sensitive to an array of model contaminants with biocide potential, including fertilizers, pesticides, metals and salts: eight out of nine tested substances were detected at the μg l -1 or mg l -1 range and triggered valve closure, decreasing filter-feeding in a concentration-dependent manner. For most toxicants, a good agreement between mortality (96 h - LC 50 within the range 0.4-5500 mg l -1 ) and feeding (2 h - IC 50 within the range 0.005-2317 mg l -1 ) was observed, demonstrating that a 120-min assay can be used as a protective surrogate of acute toxicity. However, copper sulphate was very strongly avoided by the clams (IC 50  = 5.3 μg l -1 ); on the contrary, dichlorvos (an organophosphate insecticide) did not cause feeding depression, either by being undetected by the clams' chemosensors and/or by interfering with the valve closure mechanism. Such an assay has a large potential as a simple screening tool for industry, environmental agencies and managers. The ability of dichlorvos to bypass the Asian clam's avoidance strategy puts it in the spotlight as a potential agent to be used alone or combined with others in eradication programs of this biofouler in closed or semi-closed industrial settings. Copyright © 2018 Elsevier B.V. All rights reserved.

Disseminated sporotrichosis with extensive cutaneous involvement in a patient with AIDS.

PubMed

Ware, A J; Cockerell, C J; Skiest, D J; Kussman, H M

1999-02-01

Sporotrichosis most commonly presents as a localized, lymphocutaneous infection that follows trauma, such as an injury from a rose thorn. In patients infected with HIV, it may be widespread and disseminated. We describe a patient with AIDS who developed disseminated sporotrichosis, a rare opportunistic fungal infection that may affect these patients. The condition remained undiagnosed because of failure to recognize characteristic histopathologic findings and failure of clinicians to interface closely with the microbiology laboratory. The condition was difficult to treat, requiring systemic administration of amphotericin. While localized sporotrichosis is an innocuous disorder that responds well to therapy, in immunocompromised hosts, it is potentially life-threatening and may require prolonged therapy with potentially toxic medications such as amphotericin B. It is important that clinicians be aware of the presentation of this unusual opportunistic infection and that they maintain close communication with pathology and clinical microbiology laboratories to ensure that proper stains and cultures are performed to avoid potential misdiagnosis.

Nanomedicine in pulmonary delivery

PubMed Central

Mansour, Heidi M; Rhee, Yun-Seok; Wu, Xiao

2009-01-01

The lung is an attractive target for drug delivery due to noninvasive administration via inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action for the treatment of respiratory diseases, and the availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery offer many advantages such as the potential to achieve relatively uniform distribution of drug dose among the alveoli, achievement of improved solubility of the drug from its own aqueous solubility, a sustained drug release which consequently reduces dosing frequency, improves patient compliance, decreases incidence of side effects, and the potential of drug internalization by cells. This review focuses on the current status and explores the potential of colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with special attention to their pharmaceutical aspects. Manufacturing processes, in vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines in pulmonary delivery are also discussed. PMID:20054434

Prenatal Care

MedlinePlus

... and prescription medicines you are using. These include dietary or herbal supplements. Some medicines are not safe during pregnancy. At the same time, stopping medicines you need also can be harmful. Avoid contact with toxic substances or materials at ...

[Individualized monitoring of the therapy with gentamycin using pharmacokinetic methods. Which method to choose?].

PubMed

Carvalho, A; Fonseca, C; Falcão, F; Pereira, T A; Freitas, O; Parrinha, A; Costa, M; Rodrigues, M J; Ceia, F; Luís, A S

1996-01-01

Gentamicin has an excellent cost/efficacy ratio for gram negative infections treatment. Its use is often limited in clinical practice by its narrow safety margins and a high incidence of toxicity. Gentamicin related nephrotoxicity is a major adverse effect, mostly in patients with other concomitant potential risk factors. As many other Authors we have found in our Internal Medicine Service during 1992 a gentamicin related nephrotoxicity incidence of 22.5%. Various empiric methods and nomograms have shown a significant incidence of error in predicting individualized gentamicin dosage regimens. Pharmacokinetics methods have demonstrated much better results regarding efficacy and toxicity. The aim of this prospective study carried out during 1993-1994 was to individualize by pharmacokinetics methods dosage regimens of gentamicin in patients with one or more concomitant risk factors of nephrotoxicity. The purpose of pharmacokinetics dosage regimens has been to achieve trough serum concentrations of gentamicin in therapeutics range-0.5 to 2 micrograms/ml-on the first 24 to 48 hours of treatment, and the maintenance in this range during all the treatment, avoiding both toxic and under therapeutic levels. The incidence of gentamicin related nephrotoxicity has been evaluated in this population. Twenty patients were studied: 18 males and 2 females aged 59.6 years (19 to 85). All had one or more potential risk factors for nephrotoxicity-65 years or more: 13, previous renal failure: 6, other nephrotoxic drugs: 10, diuretics: 4, dehydration: 5, congestive heart failure: 5, diabetes: 3, hypertension: 3. For the first 10 patients gentamicin dosage regimens have been determined by Sawchuk-Zaske pharmacokinetics method and for the subsequent 10 patients by Bayesian method. The two subpopulations had no significant differences regarding mean age, sex and potential risk factors for nephrotoxicity. Results of Sawchuk-Zaske method: 53 trough gentamicin serum concentration were obtained; 86.8% were within the therapeutic range, 7.5% were toxic and 5.7% were under therapeutic. Results of Bayesian method: 44 determinations of gentamicin through concentrations were obtained; 86.3% within therapeutic range, 2.4% were toxic and 11.3% were under therapeutic. A great variability in pharmacokinetic patient's profile has been found and explains the great variability of individualized dosage regimens of gentamicin (30 to 320 mg/day). No patients had gentamicin related nephrotoxicity. Both pharmacokinetics methods lead to a efficient and save employment of gentamicin in patients with previous renal failure and other potential risk factors for nephrotoxicity.

The repellent and persistent toxic effects of essential oils against the poultry red mite, Dermanyssus gallinae.

PubMed

Nechita, I S; Poirel, M T; Cozma, V; Zenner, L

2015-12-15

The economic impact of the poultry red mite, Dermanyssus gallinae, the lack of new acaricides, the occurrence of resistance and tighter legislation have all led to the need to find new ways to control this pest. One promising alternative method of control focuses on employing repellent and/or toxic effects of selected plant essential oils against D. gallinae. Ten essential oils (basil, thyme, coriander, eucalyptus, lavender, lemon, fir tree, oregano, mint, and juniper) were tested for the persistence of toxic and repellent effects. In filter-paper toxicity bioassays against D. gallinae, the best results were observed for lavender (more than 97% mortality after 48 and 72 h) and thyme (84% at 72 h) at a dose of 0.12 mg/cm(2). In addition, two oils showed significant persistent toxic effects 15 and 30 days post application to filter papers. Thyme was the most effective (100% mortality at 72 h), followed by lavender (nearly 80% mortality after 72 h). Out of the ten oils tested for their repellent effect, thyme was the strongest, with nearly 80% of the tested area avoided by mites; oregano caused a 60% avoidance and lavender exhibited an effect close to 40%. All other oils exhibited a repellent effect of less than 30%. None of the experiments showed a repellent effect for HM (commercial alimentary oil) or negative controls. We found that the thyme and lavender essential oils exhibited promising results when tested in vitro for toxic and repellent effects against D. gallinae; thus, we suggest that future experiments focus on in vivo tests using these oils in farm units. Copyright © 2015 Elsevier B.V. All rights reserved.

Dense white trichome production by plants as possible mimicry of arthropod silk or fungal hyphae that deter herbivory.

PubMed

Yamazaki, Kazuo; Lev-Yadun, Simcha

2015-01-07

Some spiders are well-known to mimic flowers or other plant surfaces in order to be cryptic to both their prey and their predators. We propose that dense, thread-like white trichomes of some plants from Estonia, Greece, Israel and Japan visually mimic spider webs, lepidopteran and spider-mite web nests and plant-pathogenic fungi, and that it may result in reduced herbivory, since various herbivores avoid spider- or other arthropod webs to circumvent predation or toxic attacks, or refrain from colonizing plants that have already been occupied by other herbivores and pathogens. Spiders and other web-forming arthropods are also the prey of certain vertebrate predators and wasps, and therefore such predators may be attracted to these web-like plant structures and prey on the invertebrate herbivores occupying them. We do not dismiss the possibility that these web-like structures may also have other defensive or physiological functions or that they are not classic mimics but rather exploit the herbivore׳s perceptual state concerning the avoidance of potentially risky objects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Toxicology research for precautionary decision-making and the role of Human & Experimental Toxicology.

PubMed

Grandjean, P

2015-12-01

A key aim of toxicology is the prevention of adverse effects due to toxic hazards. Therefore, the dissemination of toxicology research findings must confront two important challenges: one being the lack of information on the vast majority of potentially toxic industrial chemicals and the other being the strict criteria for scientific proof usually required for decision-making in regard to prevention. The present study ascertains the coverage of environmental chemicals in four volumes of Human & Experimental Toxicology and the presentation and interpretation of research findings in published articles. Links in SciFinder showed that the 530 articles published in four selected volumes between 1984 and 2014 primarily dealt with metals (126 links) and other toxicants that have received substantial attention in the past. Thirteen compounds identified by US authorities in 2006 as high-priority substances, for which toxicology documentation is badly needed, were not covered in the journal issues at all. When reviewing published articles, reliance on p values was standard, and non-significant findings were often called 'negative.' This tradition may contribute to the perceived need to extend existing research on toxic hazards that have already been well characterized. Several sources of bias towards the null hypothesis can affect toxicology research, but are generally not considered, thus adding to the current inclination to avoid false positive findings. In this regard, toxicology is particularly prone to bias because of the known paucity of false positives and, in particular, the existence of a vast number of toxic hazards which by default are considered innocuous due to lack of documentation. The Precautionary Principle could inspire decision-making on the basis of incomplete documentation and should stimulate a change in toxicology traditions and in toxicology research publication. © The Author(s) 2015.

From the Cover: A polymer library approach to suicide gene therapy for cancer

NASA Astrophysics Data System (ADS)

Anderson, Daniel G.; Peng, Weidan; Akinc, Akin; Hossain, Naushad; Kohn, Anat; Padera, Robert; Langer, Robert; Sawicki, Janet A.

2004-11-01

Optimal gene therapy for cancer must (i) deliver DNA to tumor cells with high efficiency, (ii) induce minimal toxicity, and (iii) avoid gene expression in healthy tissues. To this end, we generated a library of >500 degradable, poly(-amino esters) for potential use as nonviral DNA vectors. Using high-throughput methods, we screened this library in vitro for transfection efficiency and cytotoxicity. We tested the best performing polymer, C32, in mice for toxicity and DNA delivery after intratumor and i.m. injection. C32 delivered DNA intratumorally 4-fold better than one of the best commercially available reagents, jetPEI (polyethyleneimine), and 26-fold better than naked DNA. Conversely, the highest transfection levels after i.m. administration were achieved with naked DNA, followed by polyethyleneimine; transfection was rarely observed with C32. Additionally, polyethyleneimine induced significant local toxicity after i.m. injection, whereas C32 demonstrated no toxicity. Finally, we used C32 to deliver a DNA construct encoding the A chain of diphtheria toxin (DT-A) to xenografts derived from LNCaP human prostate cancer cells. This construct regulates toxin expression both at the transcriptional level by the use of a chimeric-modified enhancer/promoter sequence of the human prostate-specific antigen gene and by DNA recombination mediated by Flp recombinase. C32 delivery of the A chain of diphtheria toxin DNA to LNCaP xenografts suppressed tumor growth and even caused 40% of tumors to regress in size. Because C32 transfects tumors locally at high levels, transfects healthy muscle poorly, and displays no toxicity, it may provide a vehicle for the local treatment of cancer. prostate | cationic polymers

Implications for current regulatory waste toxicity characterisation methods from analysing metal and metalloid leaching from photovoltaic modules

NASA Astrophysics Data System (ADS)

Collins, Mary Kayla; Anctil, Annick

2017-07-01

The appropriateness of regulatory methods to characterise the toxicity of photovoltaic (PV) modules was investigated to quantify potential environmental impacts for modules disposed of in landfills. Because solar energy is perceived as a green technology, it is important to ensure that end-of-life issues will not be detrimental to solar energy's success. United States Environmental Protection Agency Method 1311, California waste extraction test, and modified versions of both were performed on a multi-crystalline silicon module and cells and a copper indium gallium diselenide (CIGS) module. Variations in metal leachate concentrations were found with changes in testing parameters. Lead concentrations from the multi-crystalline module ranged from 16.2 to 50.2 mg/L. Cadmium concentrations from the CIGS module ranged from 0.1 to 3.52 mg/L. This raises doubt that regulatory methods can adequately characterise PV modules. The results are useful for developing end-of-life procedures, which is a positive step towards avoiding an e-waste problem and continuing trends of increasing installation and cost reduction in the PV market.

A Robust Epoxy Resins @ Stearic Acid-Mg(OH)2 Micronanosheet Superhydrophobic Omnipotent Protective Coating for Real-Life Applications.

PubMed

Si, Yifan; Guo, Zhiguang; Liu, Weimin

2016-06-29

Superhydrophobic coating has extremely high application value and practicability. However, some difficult problems such as weak mechanical strength, the need for expensive toxic reagents, and a complex preparation process are all hard to avoid, and these problems have impeded the superhydrophobic coating's real-life application for a long time. Here, we demonstrate one kind of omnipotent epoxy resins @ stearic acid-Mg(OH)2 superhydrophobic coating via a simple antideposition route and one-step superhydrophobization process. The whole preparation process is facile, and expensive toxic reagents needed. This omnipotent coating can be applied on any solid substrate with great waterproof ability, excellent mechanical stability, and chemical durability, which can be stored in a realistic environment for more than 1 month. More significantly, this superhydrophobic coating also has four protective abilities, antifouling, anticorrosion, anti-icing, and flame-retardancy, to cope with a variety of possible extreme natural environments. Therefore, this omnipotent epoxy resins @ stearic acid-Mg(OH)2 superhydrophobic coating not only satisfies real-life need but also has great application potential in many respects.

Genetic risk variants as therapeutic targets for Crohn's disease.

PubMed

Gabbani, Tommaso; Deiana, Simona; Marocchi, Margherita; Annese, Vito

2017-04-01

The pathogenesis of Inflammatory bowel diseases (IBD) is multifactorial, with interactions between genetic and environmental factors. Despite the existence of genetic factors being largely demonstrated by epidemiological data and several genetic studies, only a few findings have been useful in term of disease prediction, disease progression and targeting therapy. Areas covered: This review summarizes the results of genome-wide association studies in Crohn's disease, the role of epigenetics and the recent discovery by genetic studies of new pathogenetic pathways. Furthermore, it focuses on the importance of applying genetic data to clinical practice, and more specifically how to better target therapy and predict potential drug-related toxicity. Expert opinion: Some genetic markers identified in Crohn`s disease have allowed investigators to hypothesize about, and in some cases, prove the usefulness of new specific therapeutic agents. However, the heterogeneity and complexity of this disease has so far limited the daily clinical use of genetic information. Finally, the study of the implications of genetics on therapy, either to predict efficacy or avoid toxicity, is considered still to be in its infancy.

Effect of Fungal Colonization of Wheat Grains with Fusarium spp. on Food Choice, Weight Gain and Mortality of Meal Beetle Larvae (Tenebrio molitor)

PubMed Central

Guo, Zhiqing; Döll, Katharina; Dastjerdi, Raana; Karlovsky, Petr; Dehne, Heinz-Wilhelm; Altincicek, Boran

2014-01-01

Species of Fusarium have significant agro-economical and human health-related impact by infecting diverse crop plants and synthesizing diverse mycotoxins. Here, we investigated interactions of grain-feeding Tenebrio molitor larvae with four grain-colonizing Fusarium species on wheat kernels. Since numerous metabolites produced by Fusarium spp. are toxic to insects, we tested the hypothesis that the insect senses and avoids Fusarium-colonized grains. We found that only kernels colonized with F. avenaceum or Beauveria bassiana (an insect-pathogenic fungal control) were avoided by the larvae as expected. Kernels colonized with F. proliferatum, F. poae or F. culmorum attracted T. molitor larvae significantly more than control kernels. The avoidance/preference correlated with larval feeding behaviors and weight gain. Interestingly, larvae that had consumed F. proliferatum- or F. poae-colonized kernels had similar survival rates as control. Larvae fed on F. culmorum-, F. avenaceum- or B. bassiana-colonized kernels had elevated mortality rates. HPLC analyses confirmed the following mycotoxins produced by the fungal strains on the kernels: fumonisins, enniatins and beauvericin by F. proliferatum, enniatins and beauvericin by F. poae, enniatins by F. avenaceum, and deoxynivalenol and zearalenone by F. culmorum. Our results indicate that T. molitor larvae have the ability to sense potential survival threats of kernels colonized with F. avenaceum or B. bassiana, but not with F. culmorum. Volatiles potentially along with gustatory cues produced by these fungi may represent survival threat signals for the larvae resulting in their avoidance. Although F. proliferatum or F. poae produced fumonisins, enniatins and beauvericin during kernel colonization, the larvae were able to use those kernels as diet without exhibiting increased mortality. Consumption of F. avenaceum-colonized kernels, however, increased larval mortality; these kernels had higher enniatin levels than F. proliferatum or F. poae-colonized ones suggesting that T. molitor can tolerate or metabolize those toxins. PMID:24932485

Taking action on developmental toxicity: Scientists’ duties to protect children

PubMed Central

2012-01-01

Background Although adaptation and proper biological functioning require developmental programming, pollutant interference can cause developmental toxicity or DT. Objectives This commentary assesses whether it is ethical for citizens/physicians/scientists to allow avoidable DT. Methods Using conceptual, economic, ethical, and logical analysis, the commentary assesses what major ethical theories and objectors would say regarding the defensibility of allowing avoidable DT. Results The commentary argues that (1) none of the four major ethical theories (based, respectively, on virtue, natural law, utility, or equity) can consistently defend avoidable DT because it unjustifiably harms, respectively, individual human flourishing, human life, the greatest good, and equality. (2) Justice also requires leaving “as much and as good” biological resources for all, including future generations possibly harmed if epigenetic change is heritable. (3) Scientists/physicians have greater justice-based duties, than ordinary/average citizens, to help stop DT because they help cause it and have greater professional abilities/opportunities to help stop it. (4) Scientists/physicians likewise have greater justice-based duties, than ordinary/average citizens, to help stop DT because they benefit more from it, given their relatively greater education/consumption/income. The paper shows that major objections to (3)-(4) fail on logical, ethical, or scientific grounds, then closes with practical suggestions for implementing its proposals. Conclusions Because allowing avoidable DT is ethically indefensible, citizens---and especially physicians/scientists---have justice-based duties to help stop DT. PMID:22963689

Taking action on developmental toxicity: scientists' duties to protect children.

PubMed

Shrader-Frechette, Kristin

2012-09-10

Although adaptation and proper biological functioning require developmental programming, pollutant interference can cause developmental toxicity or DT. This commentary assesses whether it is ethical for citizens/physicians/scientists to allow avoidable DT. Using conceptual, economic, ethical, and logical analysis, the commentary assesses what major ethical theories and objectors would say regarding the defensibility of allowing avoidable DT. The commentary argues that (1) none of the four major ethical theories (based, respectively, on virtue, natural law, utility, or equity) can consistently defend avoidable DT because it unjustifiably harms, respectively, individual human flourishing, human life, the greatest good, and equality. (2) Justice also requires leaving "as much and as good" biological resources for all, including future generations possibly harmed if epigenetic change is heritable. (3) Scientists/physicians have greater justice-based duties, than ordinary/average citizens, to help stop DT because they help cause it and have greater professional abilities/opportunities to help stop it. (4) Scientists/physicians likewise have greater justice-based duties, than ordinary/average citizens, to help stop DT because they benefit more from it, given their relatively greater education/consumption/income. The paper shows that major objections to (3)-(4) fail on logical, ethical, or scientific grounds, then closes with practical suggestions for implementing its proposals. Because allowing avoidable DT is ethically indefensible, citizens---and especially physicians/scientists---have justice-based duties to help stop DT.

Pyrrolizidine alkaloid-containing toxic plants (Senecio, Crotalaria, Cynoglossum, Amsinckia, Heliotropium, and Echium spp.).

PubMed

Stegelmeier, Bryan L

2011-07-01

Pyrrolizidine alkaloid (PA)-containing plants are found throughout the world and are probably the most common plant cause of poisoning of livestock, wildlife, and humans. PAs are potent liver toxins that under some conditions can be carcinogenic. This article briefly introduces high-risk North American PA-containing plants, summarizing their toxicity and subsequent pathology. Current diagnostic techniques, treatments, and strategies to avoid losses to PA poisoning are also reviewed. Published by Elsevier Inc.

Gustatory processing and taste memory in Drosophila

PubMed Central

Masek, Pavel; Keene, Alex C.

2018-01-01

Taste allows animals to discriminate the value and potential toxicity of food prior to ingestion. Many tastants elicit an innate attractive or avoidance response that is modifiable with nutritional state and prior experience. A powerful genetic tool kit, well-characterized gustatory system, and standardized behavioral assays make the fruit fly, Drosophila melanogaster, an excellent system for investigating taste processing and memory. Recent studies have used this system to identify the neural basis for acquired taste preference. These studies have revealed a role for dopamine-mediated plasticity of the mushroom bodies that modulate the threshold of response to appetitive tastants. The identification of neural circuitry regulating taste memory provides a system to study the genetic and physiological processes that govern plasticity within a defined memory circuit. PMID:27328844

KrioBlast TM as a New Technology of Hyper-fast Cryopreservation of Cells and Tissues. Part I. Thermodynamic Aspects and Potential Applications in Reproductive and Regenerative Medicine.

PubMed

Katkov, I I; Bolyukh, V F; Sukhikh, G T

2018-03-01

Kinetic (dynamic) vitrification is a promising trend in cryopreservation of biological materials because it allows avoiding the formation of lethal intracellular ice and minimizes harmful effects of highly toxic penetrating cryoprotectants. A uniform cooling protocol and the same instruments can be used for practically all types of cells. In modern technologies, the rate of cooling is essentially limited by the Leidenfrost effect. We describe a novel platform for kinetic vitrification of biological materials KrioBlast TM that realizes hyper-fast cooling and allows overcoming the Leidenfrost effect. This opens prospects for creation of a novel technology of cell cryopreservation for reproductive and regenerative medicine.

Toxicity of smelter slag-contaminated sediments from Upper Lake Roosevelt and associated metals to early life stage White Sturgeon (Acipenser transmontanus Richardson, 1836)

USGS Publications Warehouse

Little, E.E.; Calfee, R.D.; Linder, G.

2014-01-01

The toxicity of five smelter slag-contaminated sediments from the upper Columbia River and metals associated with those slags (cadmium, copper, zinc) was evaluated in 96-h exposures of White Sturgeon (Acipenser transmontanus Richardson, 1836) at 8 and 30 days post-hatch. Leachates prepared from slag-contaminated sediments were evaluated for toxicity. Leachates yielded a maximum aqueous copper concentration of 11.8 μg L−1 observed in sediment collected at Dead Man's Eddy (DME), the sampling site nearest the smelter. All leachates were nonlethal to sturgeon that were 8 day post-hatch (dph), but leachates from three of the five sediments were toxic to fish that were 30 dph, suggesting that the latter life stage is highly vulnerable to metals exposure. Fish maintained consistent and prolonged contact with sediments and did not avoid contaminated sediments when provided a choice between contaminated and uncontaminated sediments. White Sturgeon also failed to avoid aqueous copper (1.5–20 μg L−1). In water-only 96-h exposures of 35 dph sturgeon with the three metals, similar toxicity was observed during exposure to water spiked with copper alone and in combination with cadmium and zinc. Cadmium ranging from 3.2 to 41 μg L−1 or zinc ranging from 21 to 275 μg L−1 was not lethal, but induced adverse behavioral changes including a loss of equilibrium. These results suggest that metals associated with smelter slags may pose an increased exposure risk to early life stage sturgeon if fish occupy areas contaminated by slags.

Ecotoxicity of boric acid in standard laboratory tests with plants and soil organisms.

PubMed

Princz, Juliska; Becker, Leonie; Scheffczyk, Adam; Stephenson, Gladys; Scroggins, Rick; Moser, Thomas; Römbke, Jörg

2017-05-01

To verify the continuous sensitivity of ecotoxicological tests (mainly the test organisms), reference substances with known toxicity are regularly tested. Ideally, this substance(s) would lack specificity in its mode action, be bioavailable and readily attainable with cost-effective means of chemical characterization. Boric acid has satisfied these criteria, but has most recently been characterized as a substance of very high concern, due to reproductive effects in humans, thus limiting its recommendation as an ideal reference toxicant. However, there is probably no other chemical for which ecotoxicity in soil has been so intensively studied; an extensive literature review yielded lethal (including avoidance) and sublethal data for 38 taxa. The ecotoxicity data were evaluated using species sensitivity distributions, collectively across all taxa, and separately according to species type, endpoints, soil type and duration. The lack of specificity in the mode of action yielded broad toxicity among soil taxa and soil types, and provided a collective approach to assessing species sensitivity, while taking into consideration differences in test methodologies and exposure durations. Toxicity was species-specific with Folsomia candida and enchytraied species demonstrating the most sensitivity; among plants, the following trend occurred: dicotyledonous (more sensitive) ≫ monocotyledonous ≫ gymnosperm species. Sensitivity was also time and endpoint specific, with endpoints such as lethality and avoidance being less sensitive than reproduction effects. Furthermore, given the breadth of data and toxicity demonstrated by boric acid, lessons learned from its evaluation are discussed to recommend the properties required by an ideal reference substance for the soil compartment.

Stereotactic Body Radiation Therapy Boost After Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer: A Phase 1 Dose Escalation Study

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

Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org; Department of Radiation Oncology, Tufts Medical Center, Tufts University, Boston, Massachusetts; Leonard, Kara Lynne

Purpose: Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD). Methods and Materials: Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (<120 cc and <60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients permore » cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated. Results: Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at <24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P<.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively. Conclusions: SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.« less

Decoloration and detoxification of effluents by ionizing radiation

NASA Astrophysics Data System (ADS)

Borrely, Sueli I.; Morais, Aline V.; Rosa, Jorge M.; Badaró-Pedroso, Cintia; da Conceição Pereira, Maria; Higa, Marcela C.

2016-07-01

Three distinct textile samples were investigated for color and toxicity (S1-chemical/textile industry; S2-final textile effluent; S3 - standard textile produced effluent-untreated blue). Radiation processing of these samples were carried out at Dynamitron Electron Beam Accelerator and color and toxicity removal were determined: color removal by radiation was 96% (40 kGy, S1); 55% (2.5 kGy, S2) and 90% (2.5 kGy, S3). Concerning toxicity assays, Vibrio fischeri luminescent bacteria demonstrated higher reduction after radiation than the other systems: removal efficiencies were 33% (20 kGy, S1); 55% (2.5 kGy, S2) and 33% (2.5 kGy, S3). Daphnia similis and Brachionus plicatilis fitted well for S3 effluents. Hard toxic volumes into biological treatment plant may be avoided if radiation would be previously applied in a real plant. Results reveled how indispensable is to run toxicity to more than one living-organism.

Active avoidance from a crude oil soluble fraction by an Andean paramo copepod.

PubMed

Araújo, Cristiano V M; Moreira-Santos, Matilde; Sousa, José P; Ochoa-Herrera, Valeria; Encalada, Andrea C; Ribeiro, Rui

2014-09-01

Several oil spills due to ruptures in the pipeline oil systems have occurred at the Andean paramo. A sample of this crude oil was mixed with water from a nearby Andean lagoon and the toxicity of the soluble fraction was assessed through lethal and avoidance assays with a locally occurring copepod (Boeckella occidentalis intermedia). The integration of mortality and avoidance aimed at predicting the immediate decline of copepod populations facing an oil leakage. The 24-h median lethal PAH concentration was 42.7 (26.4-91.6) µg L(-1). In the 12-h avoidance assay, 30% avoidance was recorded at the highest PAH concentration (19.4 µg L(-1)). The mortality at this PAH concentration would be of 25% and, thus, the population immediate decline would be of 55%. The inclusion of non-forced exposure testing with the quantification of the avoidance response in environmental risk assessments is, therefore, supported due to underestimation of the lethal assays.

Mitochondrial toxicity in human pregnancy: an update on clinical and experimental approaches in the last 10 years.

PubMed

Morén, Constanza; Hernández, Sandra; Guitart-Mampel, Mariona; Garrabou, Glòria

2014-09-22

Mitochondrial toxicity can be one of the most dreadful consequences of exposure to a wide range of external agents including pathogens, therapeutic agents, abuse drugs, toxic gases and other harmful chemical substances. However, little is known about the effects of mitochondrial toxicity on pregnant women exposed to these agents that may exert transplacental activity and condition fetal remodeling. It has been hypothesized that mitochondrial toxicity may be involved in some adverse obstetric outcomes. In the present study, we investigated the association between exposure to mitochondrial toxic agents and pathologic conditions ranging from fertility defects, detrimental fetal development and impaired newborn health due to intra-uterine exposure. We have reviewed data from studies in human subjects to propose mechanisms of mitochondrial toxicity that could be associated with the symptoms present in both exposed pregnant and fetal patients. Since some therapeutic interventions or accidental exposure cannot be avoided, further research is needed to gain insight into the molecular pathways leading to mitochondrial toxicity during pregnancy. The ultimate objective of these studies should be to reduce the mitochondrial toxicity of these agents and establish biomarkers for gestational monitoring of harmful effects.

Neuraxial Analgesia In Neonates And Infants: Review of Clinical and Preclinical Strategies for the Development of Safety and Efficacy Data

PubMed Central

Walker, Suellen M.; Yaksh, Tony L.

2015-01-01

Neuraxial agents provide robust pain control, have the potential to improve outcomes, and are an important component of the perioperative care of children. Opioids or clonidine improve analgesia when added to perioperative epidural infusions; analgesia is significantly prolonged by addition of clonidine, ketamine, neostigmine or tramadol to single shot caudal injections of local anesthetic; and neonatal intrathecal anesthesia/analgesia is increasing in some centers. However, it is difficult to determine the relative risk-benefit of different techniques and drugs without detailed and sensitive data related to analgesia requirements, side-effects, and follow-up. Current data related to benefits and complications in neonates and infants are summarized, but variability in current neuraxial drug use reflects the relative lack of high quality evidence. Recent preclinical reports of adverse effects of general anesthetics on the developing brain have increased awareness of the potential benefit of neuraxial anesthesia/analgesia to avoid or reduce general anesthetic dose requirements. However, the developing spinal cord is also vulnerable to drug-related toxicity, and although there are well-established preclinical models and criteria for assessing spinal cord toxicity in adult animals, until recently there had been no systematic evaluation during early life. Therefore, the second half of this review presents preclinical data evaluating age-dependent changes in the pharmacodynamic response to different spinal analgesics, and recent studies evaluating spinal toxicity in specific developmental models. Finally, we advocate use of neuraxial agents with the widest demonstrable safety margin and suggest minimum standards for preclinical evaluation prior to adoption of new analgesics or preparations into routine clinical practice. PMID:22798528

Heavy metal toxicity to bacteria - are the existing growth media accurate enough to determine heavy metal toxicity?

PubMed

Rathnayake, I V N; Megharaj, Mallavarapu; Krishnamurti, G S R; Bolan, Nanthi S; Naidu, Ravi

2013-01-01

A new minimal medium was formulated considering the limitations of the existing media for testing heavy metal sensitivity to bacteria. Toxicity of cadmium and copper to three bacteria was investigated in the new medium and compared with three other media commonly used to study the effect of the toxic metals. Based on speciation data arrived at using ion-selective electrodes, the available free-metal concentration in solution was highest in the MES-buffered medium. This finding was strongly supported by the estimated EC(50) values for the metals tested based on the toxicity bioassays. The free-ionic cadmium and copper concentrations in the medium provide more accurate determination of metal concentrations that affects the bacteria, than with most of other existing media. This will avoid doubts on other media and misleading conclusions relevant to the toxicity of heavy metals to bacteria and provides a better option for the study of metal-bacteria interactions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Stereotactic Radiosurgery of the Postoperative Resection Cavity for Brain Metastases: Prospective Evaluation of Target Margin on Tumor Control

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

Choi, Clara Y.H.; Chang, Steven D.; Gibbs, Iris C.

2012-10-01

Purpose: Given the neurocognitive toxicity associated with whole-brain irradiation (WBRT), approaches to defer or avoid WBRT after surgical resection of brain metastases are desirable. Our initial experience with stereotactic radiosurgery (SRS) targeting the resection cavity showed promising results. We examined the outcomes of postoperative resection cavity SRS to determine the effect of adding a 2-mm margin around the resection cavity on local failure (LF) and toxicity. Patients and Methods: We retrospectively evaluated 120 cavities in 112 patients treated from 1998-2009. Factors associated with LF and distant brain failure (DF) were analyzed using competing risks analysis, with death as a competingmore » risk. The overall survival (OS) rate was calculated by the Kaplan-Meier product-limit method; variables associated with OS were evaluated using the Cox proportional hazards and log rank tests. Results: The 12-month cumulative incidence rates of LF and DF, with death as a competing risk, were 9.5% and 54%, respectively. On univariate analysis, expansion of the cavity with a 2-mm margin was associated with decreased LF; the 12-month cumulative incidence rates of LF with and without margin were 3% and 16%, respectively (P=.042). The 12-month toxicity rates with and without margin were 3% and 8%, respectively (P=.27). On multivariate analysis, melanoma histology (P=.038) and number of brain metastases (P=.0097) were associated with higher DF. The median OS time was 17 months (range, 2-114 months), with a 12-month OS rate of 62%. Overall, WBRT was avoided in 72% of the patients. Conclusion: Adjuvant SRS targeting the resection cavity of brain metastases results in excellent local control and allows WBRT to be avoided in a majority of patients. A 2-mm margin around the resection cavity improved local control without increasing toxicity compared with our prior technique with no margin.« less

Prenatal exposure of a girl with autism spectrum disorder to 'horsetail' (Equisetum arvense) herbal remedy and alcohol: a case report

PubMed Central

2011-01-01

Introduction Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences are thought to play a causal role. In humans, throughout embryonic and fetal life, brain development is exquisitely susceptible to injury caused by exposure to toxic chemicals present in the environment. Although the use of herbal supplements during pregnancy is relatively common, little information is available on their association with fetal neurodevelopment. This is, to the best of our knowledge, the first report in the literature to associate a new plausible mechanism of neurodevelopmental toxicity with a case of autism spectrum disorder through a vitamin deficiency potentiated by concomitant use of herbal supplements and ethanol exposure. Case presentation We describe the pediatric environmental history of a three-year-old Caucasian girl with an autism spectrum disorder. We utilized her pediatric environmental history to evaluate constitutional, genetic, and environmental factors pertinent to manifestation of neurodevelopment disorders. Both parents reported prenatal exposure to several risk factors of interest. A year prior to conception the mother began a weight loss diet and ingested 1200 mg/day of 'horsetail' (Equisetum arvense) herbal remedies containing thiaminase, an enzyme that with long-term use can lead to vitamin deficiency. The mother reported a significant weight loss during the pregnancy and a deficiency of B-complex vitamins. Thiamine (vitamin B1) deficiency could have been potentiated by the horsetail's thiaminase activity and ethanol exposure during pregnancy. No other risk factors were identified. Conclusions A detailed and careful pediatric environmental history, which includes daily intake, herbal remedies and ethanol exposure, should be obtained from all patients with autism spectrum disorder. Maternal consumption of ethanol and of herbal supplements with suspected or potential toxicity should be avoided during pregnancy. The prospective parents should perform preconception planning before pregnancy. PMID:21453474

Lanthanide-Substituted Magnetite Nanoparticles Using a New Mixed Precursor Method by Thermoanaerobacter ethanolicus

NASA Astrophysics Data System (ADS)

Moon, J.; Roh, Y.; Yeary, L. W.; Lauf, R. J.; Phelps, T. J.

2006-12-01

A metal reducing bacterium, Thermoanaerobacter ethanolicus successfully converted the precursor of L (lanthanide)-mixed akaganeite (LxFe1-xOOH) phase to L-substituted magnetite (LyFe3-yO4) while avoiding the potentially toxic effects of soluble L-ions. Antibiotic elements, lanthanide (Nd, Gd, Tb, Ho, and Er)-substituted magnetites were produced by microbial fermentation using LxFe1-xOOH, where x was up to 0.02 which is equivalent to 0.72 mM. Combining lanthanides into the akaganeite precursor phase mitigated some of the toxicity when compared to the traditional method by using pure akaganeite and the dissolved L-salt form. This new technique showed that an upper limit of L-concentrations between 0.02 and 0.1 mM might suppress bacterial activity. At the equivalent L-cation mole fraction, the traditional method increased the concentration of soluble toxic L ions in the final media. The precursor method enabled production of microbially synthesized L- substituted magnetite with an L-concentration 36-fold greater than could be obtained when the lanthanides were added as soluble salts. These results were confirmed by protein assay. The increase of L-concentration in the magnetite evidently manipulates its physical properties such as decreasing Curie temperature and decreasing saturation magnetism of L-substituted magnetite. This mixed precursor method can therefore be used to extend the application for nanofermentation and other bacterial synthesis fields where there is a need for economically low-energy consumable microbial production of nanoscale materials that should involve toxic or inhibitory elements to bacterial growth.

Additives for reducing the toxicity of respirable crystalline silica. SILIFE project

NASA Astrophysics Data System (ADS)

Monfort, Eliseo; López-Lilao, Ana; Escrig, Alberto; Jesus Ibáñez, Maria; Bonvicini, Guliana; Creutzenberg, Otto; Ziemann, Christina

2017-10-01

Prolonged inhalation of crystalline silica particles has long been known to cause lung inflammation and development of the granulomatous and a fibrogenic lung disease known as silicosis. The International Agency for Research on Cancer (IARC) has classified Respirable Crystalline Silica (RCS) in the form of quartz and cristobalite from occupational sources as carcinogenic for humans (category 1). In this regard, numerous studies suggest that the toxicity of quartz is conditioned by the surface chemistry of the quartz particles and by the density and abundance of silanol groups. Blocking these groups to avoid their interaction with cellular membranes would theoretically be possible in order to reduce or even to eliminate the toxic effect. In this regard, the main contribution of the presented research is the development of detoxifying processes based on coating technologies at industrial scale, since the previous studies reported on literature were carried out at lab scale. The results obtained in two European projects showed that the wet method to obtain quartz surface coatings (SILICOAT project) allows a good efficiency in inhibiting the silica toxicity, and the preliminary results obtained in an ongoing project (SILIFE) suggest that the developed dry method to coat quartz surface is also very promising. The development of both coating technologies (wet and a dry) should allow these coating technologies to be applied to a high variety of industrial activities in which quartz is processed. For this reason, a lot of end-users of quartz powders will be potentially benefited from a reduced risk associated to the exposure to RCS.

Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells.

PubMed

Kogel, U; Gonzalez Suarez, I; Xiang, Y; Dossin, E; Guy, P A; Mathis, C; Marescotti, D; Goedertier, D; Martin, F; Peitsch, M C; Hoeng, J

2015-12-01

Cigarette smoking causes serious and fatal diseases. The best way for smokers to avoid health risks is to quit smoking. Using modified risk tobacco products (MRTPs) may be an alternative to reduce the harm caused for those who are unwilling to quit smoking, but little is known about the toxic effects of MRTPs, nor were the molecular mechanisms of toxicity investigated in detail. The toxicity of an MRTP and the potential molecular mechanisms involved were investigated in high-content screening tests and whole genome transcriptomics analyses using human bronchial epithelial cells. The prototypic (p)MRTP that was tested had less impact than reference cigarette 3R4F on the cellular oxidative stress response and cell death pathways. Higher pMRTP aerosol extract concentrations had impact on pathways associated with the detoxification of xenobiotics and the reduction of oxidative damage. A pMRTP aerosol concentration up to 18 times higher than the 3R4F caused similar perturbation effects in biological networks and led to the perturbation of networks related to cell stress, and proliferation biology. These results may further facilitate the development of a systems toxicology-based impact assessment for use in future risk assessments in line with the 21st century toxicology paradigm, as shown here for an MRTP. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessing subunit dependency of the Plasmodium proteasome using small molecule inhibitors and active site probes.

PubMed

Li, Hao; van der Linden, Wouter A; Verdoes, Martijn; Florea, Bogdan I; McAllister, Fiona E; Govindaswamy, Kavitha; Elias, Joshua E; Bhanot, Purnima; Overkleeft, Herman S; Bogyo, Matthew

2014-08-15

The ubiquitin-proteasome system (UPS) is a potential pathway for therapeutic intervention for pathogens such as Plasmodium, the causative agent of malaria. However, due to the essential nature of this proteolytic pathway, proteasome inhibitors must avoid inhibition of the host enzyme complex to prevent toxic side effects. The Plasmodium proteasome is poorly characterized, making rational design of inhibitors that induce selective parasite killing difficult. In this study, we developed a chemical probe that labels all catalytic sites of the Plasmodium proteasome. Using this probe, we identified several subunit selective small molecule inhibitors of the parasite enzyme complex. Treatment with an inhibitor that is specific for the β5 subunit during blood stage schizogony led to a dramatic decrease in parasite replication while short-term inhibition of the β2 subunit did not affect viability. Interestingly, coinhibition of both the β2 and β5 catalytic subunits resulted in enhanced parasite killing at all stages of the blood stage life cycle and reduced parasite levels in vivo to barely detectable levels. Parasite killing was achieved with overall low host toxicity, something that has not been possible with existing proteasome inhibitors. Our results highlight differences in the subunit dependency of the parasite and human proteasome, thus providing a strategy for development of potent antimalarial drugs with overall low host toxicity.

Plant Insecticide L-Canavanine Repels Drosophila via the Insect Orphan GPCR DmX

PubMed Central

Framery, Bérénice; Bockaert, Joël; Parmentier, Marie-Laure; Grau, Yves

2009-01-01

For all animals, the taste sense is crucial to detect and avoid ingesting toxic molecules. Many toxins are synthesized by plants as a defense mechanism against insect predation. One example of such a natural toxic molecule is l-canavanine, a nonprotein amino acid found in the seeds of many legumes. Whether and how insects are informed that some plants contain l-canavanine remains to be elucidated. In insects, the taste sense relies on gustatory receptors forming the gustatory receptor (Gr) family. Gr proteins display highly divergent sequences, suggesting that they could cover the entire range of tastants. However, one cannot exclude the possibility of evolutionarily independent taste receptors. Here, we show that l-canavanine is not only toxic, but is also a repellent for Drosophila. Using a pharmacogenetic approach, we find that flies sense food containing this poison by the DmX receptor. DmXR is an insect orphan G-protein–coupled receptor that has partially diverged in its ligand binding pocket from the metabotropic glutamate receptor family. Blockade of DmXR function with an antagonist lowers the repulsive effect of l-canavanine. In addition, disruption of the DmXR encoding gene, called mangetout (mtt), suppresses the l-canavanine repellent effect. To avoid the ingestion of l-canavanine, DmXR expression is required in bitter-sensitive gustatory receptor neurons, where it triggers the premature retraction of the proboscis, thus leading to the end of food searching. These findings show that the DmX receptor, which does not belong to the Gr family, fulfills a gustatory function necessary to avoid eating a natural toxin. PMID:19564899

Mineralogical and geochemical characterization of waste rocks from a gold mine in northeastern Thailand: application for environmental impact protection.

PubMed

Assawincharoenkij, Thitiphan; Hauzenberger, Christoph; Ettinger, Karl; Sutthirat, Chakkaphan

2018-02-01

Waste rocks from gold mining in northeastern Thailand are classified as sandstone, siltstone, gossan, skarn, skarn-sulfide, massive sulfide, diorite, and limestone/marble. Among these rocks, skarn-sulfide and massive sulfide rocks have the potential to generate acid mine drainage (AMD) because they contain significant amounts of sulfide minerals, i.e., pyrrhotite, pyrite, arsenopyrite, and chalcopyrite. Moreover, both sulfide rocks present high contents of As and Cu, which are caused by the occurrence of arsenopyrite and chalcopyrite, respectively. Another main concern is gossan contents, which are composed of goethite, hydrous ferric oxide (HFO), quartz, gypsum, and oxidized pyroxene. X-ray maps using electron probe micro-analysis (EPMA) indicate distribution of some toxic elements in Fe-oxyhydroxide minerals in the gossan waste rock. Arsenic (up to 1.37 wt.%) and copper (up to 0.60 wt.%) are found in goethite, HFO, and along the oxidized rim of pyroxene. Therefore, the gossan rock appears to be a source of As, Cu, and Mn. As a result, massive sulfide, skarn-sulfide, and gossan have the potential to cause environmental impacts, particularly AMD and toxic element contamination. Consequently, the massive sulfide and skarn-sulfide waste rocks should be protected from oxygen and water to avoid an oxidizing environment, whereas the gossan waste rocks should be protected from the formation of AMD to prevent heavy metal contamination.

Publication visibility of sensitive public health data: when scientists bury their results.

PubMed

Rier, David A

2004-10-01

What happens when the scientific tradition of openness clashes with potential societal risks? The work of American toxic-exposure epidemiologists can attract media coverage and lead the public to change health practices, initiate lawsuits, or take other steps a study's authors might consider unwarranted. This paper, reporting data from 61 semi-structured interviews with U.S. toxic-exposure epidemiologists, examines whether such possibilities shaped epidemiologists' selection of journals for potentially sensitive papers. Respondents manifested strong support for the norm of scientific openness, but a significant minority had or would/might, given the right circumstances, publish sensitive data in less visible journals, so as to prevent unwanted media or public attention. Often, even those advocating such limited "burial" upheld openness, claiming that less visible publication allowed them to avoid totally withholding the data from publication. However, 15% of the sample had or would, for the most sensitive types of data, withhold publication altogether. Rather than respondents explaining their actions in terms of an expected split between "pure science" and "social advocacy" models, even those publishing in the more visible journals often described their actions in terms of their "responsibility". Several practical limitations (particularly involving broader access to scientific literature via the Internet) of the strategy of burial are discussed, and some recommendations are offered for scientists, the media, and the public.

Avoiding false positives and optimizing identification of true ...

EPA Pesticide Factsheets

The potential for chemicals to affect endocrine signaling is commonly evaluated via in vitro receptor binding and gene activation, but these assays, especially antagonism assays, have potential artifacts that must be addressed for accurate interpretation. Results are presented from screening 94 chemicals from 54 chemical groups for estrogen receptor (ER) activation in a competitive rainbow trout ER (rtER) binding assay and a trout liver slice vitellogenin mRNA expression assay. Results from true competitive agonists and antagonists, and inactive chemicals with little or no indication of ER binding or gene activation were easily interpreted. However, results for numerous industrial chemicals were more challenging to interpret, including chemicals with: (1) apparent competitive binding curves but no gene activation, (2) apparent binding and gene inhibition with evidence of either cytotoxicity or changes in assay media pH, (3) apparent binding but non-competitive gene inhibition of unknown cause, or (4) no rtER binding and gene inhibition not due to competitive ER interaction but due to toxicity, pH change, or some unknown cause. The use of endpoints such as toxicity, pH, precipitate formation, and determination of inhibitor dissociation constants (Ki) for interpreting the results of antagonism and binding assays for diverse chemicals is presented. Of the 94 chemicals tested for antagonism only two, tamoxifen and ICI-182,780, were found to be true competitive

Progress in understanding the molecular oxygen paradox - function of mitochondrial reactive oxygen species in cell signaling.

PubMed

Kuksal, Nidhi; Chalker, Julia; Mailloux, Ryan J

2017-10-26

The molecular oxygen (O2) paradox was coined to describe its essential nature and toxicity. The latter characteristic of O2 is associated with the formation of reactive oxygen species (ROS), which can damage structures vital for cellular function. Mammals are equipped with antioxidant systems to fend off the potentially damaging effects of ROS. However, under certain circumstances antioxidant systems can become overwhelmed leading to oxidative stress and damage. Over the past few decades, it has become evident that ROS, specifically H2O2, are integral signaling molecules complicating the previous logos that oxyradicals were unfortunate by-products of oxygen metabolism that indiscriminately damage cell structures. To avoid its potential toxicity whilst taking advantage of its signaling properties, it is vital for mitochondria to control ROS production and degradation. H2O2 elimination pathways are well characterized in mitochondria. However, less is known about how H2O2 production is controlled. The present review examines the importance of mitochondrial H2O2 in controlling various cellular programs and emerging evidence for how production is regulated. Recently published studies showing how mitochondrial H2O2 can be used as a secondary messenger will be discussed in detail. This will be followed with a description of how mitochondria use S-glutathionylation to control H2O2 production.

New targeted therapies and diagnostic methods for iron overload diseases.

PubMed

Kolnagou, Annita; Kontoghiorghe, Christina N; Kontoghiorghes, George John

2018-01-01

Millions of people worldwide suffer from iron overload toxicity diseases such as transfusional iron overload in thalassaemia and hereditary haemochromatosis. The accumulation and presence of toxic focal iron deposits causing tissue damage can also be identified in Friedreich's ataxia, Alzheimer's, Parkinson's, renal and other diseases. Different diagnostic criteria of toxicity and therapeutic interventions apply to each disease of excess or misplaced iron. Magnetic resonance imaging relaxation times T2 and T2* for monitoring iron deposits in organs and iron biomarkers such as serum ferritin and transferrin iron saturation have contributed in the elucidation of iron toxicity mechanisms and pathways, and also the evaluation of the efficacy and mode of action of chelating drugs in the treatment of diseases related to iron overload, toxicity and metabolism. Similarly, histopathological and electron microscopy diagnostic methods have revealed mechanisms of iron overload toxicity at cellular and sub-cellular levels. These new diagnostic criteria and chelator dose adjustments could apply in different or special patient categories e.g. thalassaemia patients with normal iron stores, where iron deficiency and over-chelation toxicity should be avoided.

Exploring the Impact of Toxic Attitudes and a Toxic Environment on the Veterinary Healthcare Team.

PubMed

Moore, Irene C; Coe, Jason B; Adams, Cindy L; Conlon, Peter D; Sargeant, Jan M

2015-01-01

The objective of this qualitative study was to compare veterinarians' and Registered Veterinary Technicians' (RVT's) perceptions of the veterinary healthcare team with respect to the impact of toxic attitudes and a toxic environment. Focus group interviews using a semi-structured interview guide and follow up probes were held with four veterinarian groups (23 companion animal veterinarians) and four Registered Veterinary Technician groups (26 RVTs). Thematic analysis of the discussions indicated both veterinarian and RVT participants felt team members with manifestations of toxic attitudes negatively impacted veterinary team function. These manifestations included people being disrespectful, being resistant to change, always wanting to be the "go to person," avoiding conflict, and lacking motivation. When conflict was ignored, or when people with toxic attitudes were not addressed, a toxic environment often resulted. A toxic environment sometimes manifested when "broken communication and tension between staff members" occurred as a result of employees lacking confidence, skills, or knowledge not being managed properly. It also occurred when employees did not feel appreciated, when there was difficulty coping with turnover, and when there were conflicting demands. The presence of people manifesting a toxic attitude was a source of frustration for both veterinarian and RVT participants. Prompt and consistent attention to negative behaviors is recommended to reduce the development of a toxic environment.

Assessment of in vivo organ-uptake and in silico prediction of CYP mediated metabolism of DA-Phen, a new dopaminergic agent.

PubMed

Sutera, Flavia Maria; Giannola, Libero Italo; Murgia, Denise; De Caro, Viviana

2017-12-01

The drug development process strives to predict metabolic fate of a drug candidate, together with its uptake in major organs, whether they act as target, deposit or metabolism sites, to the aim of establish a relationship between the pharmacodynamics and the pharmacokinetics and highlight the potential toxicity of the drug candidate. The present study was aimed at evaluating the in vivo uptake of 2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) - a new dopaminergic neurotransmission modulator, in target and non-target organs of animal subjects and integrating these data with SMARTCyp results, an in silico method that predicts the sites of cytochrome P450-mediated metabolism of drug-like molecules. Wistar rats, subjected to two different behavioural studies in which DA-Phen was intraperitoneally administrated at a dose equal to 0.03mmol/kg, were sacrificed after the experimental protocols and their major organs were analysed to quantify the drug uptake. The data obtained were integrated with in silico prediction of potential metabolites of DA-Phen using the SmartCYP predictive tool. DA-Phen reached quantitatively the Central Nervous System and the results showed that the amide bond of the DA-Phen is scarcely hydrolysed as it was found intact in analyzed organs. As a consequence, it is possible to assume that DA-Phen acts as dopaminergic modulator per se and not as a Dopamine prodrug, thus avoiding peripheral release and toxic side effects due to the endogenous neurotransmitter. Furthermore the identification of potential metabolites related to biotransformation of the drug candidate leads to a more careful evaluation of the appropriate route of administration for future intended therapeutic aims and potential translation into clinical studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Jatropha curcas oil in Lactuca sativa root tip bioassays.

PubMed

Andrade-Vieira, Larissa F; Botelho, Carolina M; Laviola, Bruno G; Palmieri, Marcel J; Praça-Fontes, Milene M

2014-03-01

Jatropha curcas L. (Euphorbiaceae) is important for biofuel production and as a feed ingredient for animal. However, the presence of phorbol esters in the oil and cake renders the seeds toxic. The toxicity of J. curcas oil is currently assessed by testing in animals, leading to their death. The identification of toxic and nontoxic improved varieties is important for the safe use of J. curcas seeds and byproducts to avoid their environmental toxicity. Hence, the aim of this study was to propose a short-term bioassay using a plant as a model to screen the toxicity of J. curcas oil without the need to sacrifice any animals. The toxicity of J. curcas oil was evident in germination, root elongation and chromosomal aberration tests in Lactuca sativa. It was demonstrated that J. curcas seeds contain natural compounds that exert phyto-, cyto- and genotoxic effects on lettuce, and that phorbol esters act as aneugenic agents, leading to the formation of sticky chromosomes and c-metaphase cells. In conclusion, the tests applied have shown reproducibility, which is important to verify the extent of detoxification and to determine toxic doses, thus reducing the numbers of animals that would be used for toxicity tests.

Avoidance behaviour response and esterase inhibition in the earthworm, Lumbricus terrestris, after exposure to chlorpyrifos.

PubMed

Martínez Morcillo, S; Yela, J L; Capowiez, Y; Mazzia, C; Rault, M; Sanchez-Hernandez, Juan C

2013-05-01

The avoidance response of earthworms to polluted soils has been standardised using a simple and low-cost test, which facilitates soil toxicity screening. In this study, the avoidance response of Lumbricus terrestris was quantified in chlorpyrifos-spiked soils, depending on the pesticide concentration and exposure duration. The inhibition of acetylcholinesterase (AChE) and carboxylesterase (CbE) activities was also determined as indirect measures of pesticide bioavailability. The effects of different chlorpyrifos concentrations were examined in a standardised test (two-chamber system) with 0.6, 3 and 15 mg/kg chlorpyrifos. A modification of the test involved a pre-exposure step (24, 48 or 72 h) in soils spiked with 15 mg/kg. In both protocols, earthworms were unable to avoid the contaminated soils. However, the esterase activities showed that all earthworms were exposed to chlorpyrifos. Acetylcholinesterase activity did not change in earthworms in the standardised behavioural test (0.58 ± 0.20 U/mg protein, mean ± SD; n = 72), whereas the CbE activity was significantly inhibited (62-87 % inhibition) in earthworms exposed to 3 and 15 mg/kg. In the modified test, earthworms had greatly inhibited AChE activity (0.088 ± 0.034 U/mg protein, n = 72), which was supported by reactivation of the inhibited enzyme activity in the presence of pralidoxime (2-PAM). Similarly, the CbE activity was significantly inhibited in earthworms with all treatments. This study suggests that the avoidance behaviour test for organophosphorus-contaminated soils could be supported by specific biomarkers to facilitate a better understanding of pesticide exposure and toxicity during this test.

Contaminants as habitat disturbers: PAH-driven drift by Andean paramo stream insects.

PubMed

Araújo, Cristiano V M; Moreira-Santos, Matilde; Sousa, José P; Ochoa-Herrera, Valeria; Encalada, Andrea C; Ribeiro, Rui

2014-10-01

Contaminants can behave as toxicants, when toxic effects are observed in organisms, as well as habitat disturbers and fragmentors, by triggering avoidance responses and generating less- or uninhabited zones. Drift by stream insects has long been considered a mechanism to avoid contamination by moving to most favorable habitats. Given that exploration and transportation of crude oil represent a threat for surrounding ecosystems, the key goal of the present study was to assess the ability of autochthonous groups of aquatic insects from the Ecuadorian paramo streams to avoid by drift different concentrations of polycyclic aromatic hydrocarbons (PAH) contained in the soluble fraction of locally transported crude oil. In the laboratory, different groups of insects were exposed to PAH for 12h. Three different assays, which varied in taxa and origin of the organisms, concentrations of PAH (0.6-38.8µgL(-1)), and environment settings (different levels of refuge and flow) were performed. For Anomalocosmoecus palugillensis (Limnephilidae), drift was a major cause of population decline in low concentration treatments but at higher concentrations mortality dominated. PAH was highly lethal, even at lower concentrations, for Chironomidae, Grypopterygidae (Claudioperla sp.) and Hydrobiosidae (Atopsyche sp.), and, therefore, no conclusion about drift can be drawn for these insects. Contamination by PAH showed to be a threat for benthic aquatic insects from Ecuadorian paramo streams as it can cause a population decline due to avoidance by drift and mortality. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative ecotoxicity of chlorantraniliprole to non-target soil invertebrates.

PubMed

Lavtižar, Vesna; Berggren, Kristina; Trebše, Polonca; Kraak, Michiel H S; Verweij, Rudo A; van Gestel, Cornelis A M

2016-09-01

The insecticide chlorantraniliprole (CAP) is gaining importance in agricultural practice, but data on its possible negative effects on non-target organisms is severely deficient. This study therefore determined CAP toxicity to non-target soil invertebrates playing a crucial role in ecosystem functioning, including springtails (Folsomia candida), isopods (Porcellio scaber), enchytraeids (Enchytraeus crypticus) and oribatid mites (Oppia nitens). In sublethal toxicity tests in Lufa 2.2 soil, chronic exposure to CAP concentrations up to 1000 mg/kgdw did not affect the survival and reproduction of E. crypticus and O. nitens nor the survival, body weight and consumption of P. scaber. In contrast, the survival and reproduction of F. candida was severely affected, with an EC50 for effects on reproduction of 0.14 mg CAP/kgdw. The toxicity of CAP to the reproduction of F. candida was tested in four different soils following OECD guideline 232, and additionally in an avoidance test according to ISO guideline 17512-2. A significantly lower toxicity in soils rich in organic matter was observed, compared to low organic soils. Observations in the avoidance test with F. candida suggest that CAP acted in a prompt way, by affecting collembolan locomotor abilities thus preventing them from escaping contaminated soil. This study shows that CAP may especially pose a risk to non-target soil arthropods closely related to insects, while other soil invertebrates seem rather insensitive. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of acute tacrine treatment on passive-avoidance response, open-field behavior, and toxicity in 17- and 30-day-old mice.

PubMed

Pan, S Y; Han, Y F; Yu, Z L; Yang, R; Dong, H; Ko, K M

2006-09-01

The potential of tacrine in altering cognitive/behavioral function as well as in causing toxicity was evaluated in mice of 17 and 30 days of age. Cognitive and behavioral studies were performed using a step-through passive avoidance task and a habituation open-field test with a 24-h retention interval. Tacrine was subcutaneously injected (1.25-80 micro mol/kg) 30 min prior to the first session of both tests. During the training session in step-through task, tacrine treatment dose-dependently decreased the number of footshocks, with IC(50) values being 7.8 and 23.3 micro mol/kg in 17- and 30-day-old mice, respectively. Treatment with tacrine at a low dose (5 micro mol/kg) significantly prolonged the retention latency in 17-day-old mice only, but it shortened the retention latency at high doses of 20 and 40 micro mol/kg in 17- and 30-day-old, respectively. During the acquisition session in the open-field test, tacrine treatment dose-dependently decreased the locomotor activity in 17- and 30-day-old mice, with IC(50) values being 15.1 and 24.7 micro mol/kg, respectively. High doses of tacrine invariably increased the locomotor activity during the recall session. Tacrine treatment at a dose of 40 micro mol/kg caused a significant increase in serum alanine aminotransferase activity in 17- and 30-day-old mice at 6 h post-dosing, with the extent of stimulation in 30-day-old mice being more prominent. In conclusion, tacrine was more potent in enhancing/disrupting the cognitive function, inhibiting locomotor activity as well as in causing hepatotoxicity in 17-day-old than in 30-day-old mice.

Behavioural ecotoxicology, an “early warning” signal to assess environmental quality

PubMed Central

2010-01-01

Background In this review, the position of behavioural ecotoxicology within the available means to assess the status of marine environments is described as filling the gap for the needed “early warning” signals. A few examples of studies performed since the 1960s are discussed to highlight the sensitivity of these approaches in investigating the effects of chemicals, including priority pollutants and emerging contaminants, relative to conventional toxicity tests measuring survival. Discussion The advantage of the behavioural response is due to the integration of biochemical and physiological processes that reflect changes at higher levels of organisation with ecological relevance. Avoidance often represents a behavioural symptom easily detected in many animals exposed to contaminants and would be a useful test to explore more widely. This rapid response would reflect a defence mechanism protective against further exposure and the potential development of more pronounced deleterious effects, whilst in some cases, escape could lead to the relocation of a species with negative consequences. An investigation of the avoidance behaviour of mud shrimp, Corophium volutator, along with the chemical analyses of sediments and amphipods to assess the quality of harbour sediments is summarised. The body burden of the amphipods was 1,000 times lower than the one associated with narcosis, emphasizing the sensitivity of this endpoint. The application of this acute toxicity test is briefly compared to additional work that involved intertidal mussels collected in the field. Conclusions Recent research undertaken with mud snails, Ilyanassa obsoleta, and harbour sediments confirmed the usefulness of the escape behaviour as an assessment tool. However, the limits of the state of knowledge regarding the fate of contaminants in species with the ability to metabolise contaminants is further discussed along with directions to be pursued to address questions arising from the reviewed literature. PMID:20614196

Ecotoxicity and biodegradability of new brominated flame retardants: a review.

PubMed

Ezechiáš, M; Covino, S; Cajthaml, T

2014-12-01

Brominated flame retardants (BFRs) have been routinely used as additives in a number of consumer products for several decades in order to reduce the risk of fire accidents. Concerns about the massive use of these substances have increased due to their possible toxicity, endocrine disrupting properties and occurrence in almost all the environmental compartments, including humans and wildlife organisms. Several conventional BFRs (e.g. polybrominated diphenylethers (PBDE)) have been included in the list of Persistent Organic Pollutants and their use has been restricted because of their established toxicity and environmental persistence. Over the past few years, these compounds have been replaced with "new" BFRs (NBFRs). Despite the fact that NBFRs are different chemical molecules than traditional BFRs, most of physical-chemical properties (e.g. aromatic moiety, halogen substitution, lipophilic character) are common to both groups; therefore, their fate in the environment is potentially similar to the banned BFRs. Therefore, this article has been compiled to summarize the published scientific data regarding the biodegradability of the most widely used NBFRs, a key factor in their potential persistency in the environment, and their ecotoxicological effects on humans and test organisms. The data reviewed here document that the mechanisms through NBFRs exibit their ecotoxicity and the processes leading to their biotransformation in the environment are still poorly understood. Thus emphasis is placed on the need for further research in these areas is therefore emphasized, in order to avoid the massive use of further potentially harmful and recalcitrant substances of anthropogenic origin. Copyright © 2014 Elsevier Inc. All rights reserved.

Neuroprotective effects of phloretin and its glycosylated derivative on rotenone-induced toxicity in human SH-SY5Y neuronal-like cells.

PubMed

Barreca, Davide; Currò, Monica; Bellocco, Ersilia; Ficarra, Silvana; Laganà, Giuseppina; Tellone, Ester; Laura Giunta, Maria; Visalli, Giuseppa; Caccamo, Daniela; Galtieri, Antonio; Ientile, Riccardo

2017-07-08

Phloretin and phlorizin are the two strong natural antioxidants whose biological and pharmacological applications are rapidly growing in different human pathological conditions. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells. The neuroprotective activity of the two flavonoids has been analyzed on cell culture of neuroblastoma cells and evaluated by testing cell vitality, mitochondrial transmembrane potential and ROS production, antioxidant enzymes detection, activation of caspase 3, DNA damage, protein carbonylation, lipid peroxidation, and superoxide anion scavenging activity. Incubation of cells with rotenone caused cell death and significant increase in intracellular reactive oxygen species, activation of caspase 3, and variation in mitochondrial transmembrane potential. Although, rotenone exposure caused a significant increase of antioxidant enzymes, high levels of lipid peroxidation were also observed. Phloretin or phlorizin, at micromolar concentration, reduced rotenone-induced cell death by scavenging ability against superoxide anion radical, one of the main effectors of rotenone toxicity at level of mitochondrial respiratory chain complex I. Under our experimental conditions, a reduction of the intracellular ROS levels with consequent normalization of the aforementioned antioxidant enzymes occurred. Concomitantly, we observed the inhibition of caspase 3 activity and DNA damage. This study shows the promising neuroprotective ability of the two dihydrochalcones able to protect human differentiated neuroblastoma cells (commonly used as model of Parkinson's disease) from injury induced by rotenone, actively scavenging ROS, normalizing mitochondrial transmembrane potential and consequently avoiding energy depletion. © 2017 BioFactors, 43(4):549-557, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Treatment of diabetes with encapsulated pig islets: an update on current developments*

PubMed Central

Zhu, Hai-tao; Lu, Lu; Liu, Xing-yu; Yu, Liang; Lyu, Yi; Wang, Bo

2015-01-01

The potential use of allogeneic islet transplantation in curing type 1 diabetes mellitus has been adequately demonstrated, but its large-scale application is limited by the short supply of donor islets and the need for sustained and heavy immunosuppressive therapy. Encapsulation of pig islets was therefore suggested with a view to providing a possible alternative source of islet grafts and avoiding chronic immunosuppression and associated adverse or toxic effects. Nevertheless, several vital elements should be taken into account before this therapy becomes a clinical reality, including cell sources, encapsulation approaches, and implantation sites. This paper provides a comprehensive review of xenotransplantation of encapsulated pig islets for the treatment of type 1 diabetes mellitus, including current research findings and suggestions for future studies. PMID:25990050

Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease.

PubMed

Bakker, Jaap A; Drent, Marjolein; Bierau, Jörgen

2007-09-01

Mercaptopurine therapy is increasingly important as immunosuppressive therapy in interstitial lung disease. We focus on human mercaptopurine metabolism and the defects in this metabolism causing adverse drug reactions. Defects in mercaptopurine metabolizing enzymes like thiopurine methyltransferase and inosine triphosphate pyrophosphohydrolase lead to severe adverse drug reactions, sometimes with fatal outcome. Other enzymes, still not thoroughly investigated, can give rise to toxic effects or decreased efficacy in mercaptopurine therapy when the activity of these enzymes is altered. Pharmacogenetic screening of potential patients for mercaptopurine therapy is important to avoid adverse drug reactions caused by inherited enzyme deficiencies in these metabolic pathways. Pretreatment screening for deficiencies of mercaptopurine metabolizing enzymes will significantly reduce the number of patients with an adverse drug reaction and concomitantly associated healthcare costs.

Using QR codes to enable quick access to information in acute cancer care.

PubMed

Upton, Joanne; Olsson-Brown, Anna; Marshall, Ernie; Sacco, Joseph

2017-05-25

Quick access to toxicity management information ensures timely access to steroids/immunosuppressive treatment for cancer patients experiencing immune-related adverse events, thus reducing length of hospital stays or avoiding hospital admission entirely. This article discusses a project to add a QR (quick response) code to a patient-held immunotherapy alert card. As QR code generation is free and the immunotherapy clinical management algorithms were already publicly available through the trust's clinical network website, the costs of integrating a QR code into the alert card, after printing, were low, while the potential benefits are numerous. Patient-held alert cards are widely used for patients receiving anti-cancer treatment, and this established standard of care has been modified to enable rapid access of information through the incorporation of a QR code.

Glycosyltransferases in secondary plant metabolism: tranquilizers and stimulant controllers.

PubMed

Jones, P; Vogt, T

2001-06-01

Plants are exposed to a wide range of toxic and bioactive low-molecular-weight molecules from both exogenous and endogenous sources. Glycosylation is one of the primary sedative mechanisms that plants utilise in order to maintain metabolic homeostasis. Recently, a range of glycosyltransferases has been characterized in detail with regard to substrate specificity. The next step in increasing our understanding of the biology of glycosylation will require information regarding the exact role of individual glycosyltransferases in planta, as well as an insight into their potential involvement in metabolon-complexes. Hopefully, this will answer how a large number of glycosyltransferases with broad, rather than narrow, substrate specificity can be constrained in order to avoid interfering with other pathways of primary and secondary metabolism. These and other topics are discussed.

[Abnormal hepatic function tests in pregnancy: causes and consequences].

PubMed

Nemesánszky, Elemér

2013-07-21

The well-known normal ranges of laboratory parameters are altered due to the broad spectrum of physiological changes as well as proinflammatory and procoagulant effects of pregnancy. Hepatic disorders of any aetiology can cause potential problems during gravidity. Most frequently toxic-effects, hepatotrop viruses (such as hepatitis B and C), metabolic syndrome and diseases with autoimmune background can be observed. When dealing with "pregnancy-specific hepatic syndromes", it is very important to consider the "timing-factors" of pathologic changes and deterioration of clinical pictures as well. Due to the progress in cholestasis management, early termination of pregnancy can be avoided in many cases. As the overlap is really broad between various hepatic disorders, a multidisciplinary cooperation of different sub-disciplines is emphasized in order to achieve proper diagnosis and curative measures at early phase.

Pesticide Toxicity Index: a tool for assessing potential toxicity of pesticide mixtures to freshwater aquatic organisms

USGS Publications Warehouse

Nowell, Lisa H.; Norman, Julia E.; Moran, Patrick W.; Martin, Jeffrey D.; Stone, Wesley W.

2014-01-01

Pesticide mixtures are common in streams with agricultural or urban influence in the watershed. The Pesticide Toxicity Index (PTI) is a screening tool to assess potential aquatic toxicity of complex pesticide mixtures by combining measures of pesticide exposure and acute toxicity in an additive toxic-unit model. The PTI is determined separately for fish, cladocerans, and benthic invertebrates. This study expands the number of pesticides and degradates included in previous editions of the PTI from 124 to 492 pesticides and degradates, and includes two types of PTI for use in different applications, depending on study objectives. The Median-PTI was calculated from median toxicity values for individual pesticides, so is robust to outliers and is appropriate for comparing relative potential toxicity among samples, sites, or pesticides. The Sensitive-PTI uses the 5th percentile of available toxicity values, so is a more sensitive screening-level indicator of potential toxicity. PTI predictions of toxicity in environmental samples were tested using data aggregated from published field studies that measured pesticide concentrations and toxicity to Ceriodaphnia dubia in ambient stream water. C. dubia survival was reduced to ≤ 50% of controls in 44% of samples with Median-PTI values of 0.1–1, and to 0% in 96% of samples with Median-PTI values > 1. The PTI is a relative, but quantitative, indicator of potential toxicity that can be used to evaluate relationships between pesticide exposure and biological condition.

Interactions in the Metabolism of Glutamate and the Branched-Chain Amino Acids and Ketoacids in the CNS.

PubMed

Yudkoff, Marc

2017-01-01

Glutamatergic neurotransmission entails a tonic loss of glutamate from nerve endings into the synapse. Replacement of neuronal glutamate is essential in order to avoid depletion of the internal pool. In brain this occurs primarily via the glutamate-glutamine cycle, which invokes astrocytic synthesis of glutamine and hydrolysis of this amino acid via neuronal phosphate-dependent glutaminase. This cycle maintains constancy of internal pools, but it does not provide a mechanism for inevitable losses of glutamate N from brain. Import of glutamine or glutamate from blood does not occur to any appreciable extent. However, the branched-chain amino acids (BCAA) cross the blood-brain barrier swiftly. The brain possesses abundant branched-chain amino acid transaminase activity which replenishes brain glutamate and also generates branched-chain ketoacids. It seems probable that the branched-chain amino acids and ketoacids participate in a "glutamate-BCAA cycle" which involves shuttling of branched-chain amino acids and ketoacids between astrocytes and neurons. This mechanism not only supports the synthesis of glutamate, it also may constitute a mechanism by which high (and potentially toxic) concentrations of glutamate can be avoided by the re-amination of branched-chain ketoacids.

Psychological aspects of personnel contamination

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

Wilson, R.L.

1985-04-01

This paper discusses some of the major emotional considerations involved in the treatment of people who have been contaminated with potentially hazardous materials. Although the principal focus is the treatment of people trained to work with these materials, an attempt is also made to extend these methods to people having little or no knowledge of such matters. Accidents always result in emotional trauma. When the accident involves radioactive or other potentially toxic, carcinogenic, or mutagenic materials, there is a possibility of enhanced emotional stress due to the mystique surrounding these substances. Several psychological principles that have emerged from the treatmentmore » of radioactively-contaminated workers are: (1) provide pre-accident training for all radiation workers; (2) avoid secrets; (3) as rapidly as possible following a contamination accident, bring the worker into contact with others; (4) recognize the emotions of the family and the family's fears and trauma; and (5) do not desert the worker after decontamination has been completed. 1 ref.« less

Sicklepod (Senna obtusifolia) seed processing and potential utilization.

PubMed

Harry-O'kuru, Rogers E; Wu, Y Victor; Evangelista, Roque; Vaughn, Steven F; Rayford, Warren; Wilson, Richard F

2005-06-15

Sicklepod (Senna obtusifolia) is a leguminous plant that infests soybean fields in the southeastern United States. Its seeds contain a variety of toxic, highly colored compounds, mainly anthraquinones together with a small amount of fat. These compounds contaminate and lower the quality of soybean oil when inadequately cleaned soybean seed from this area is processed. The sorting of sicklepod seed from a soybean harvest is an additional economic burden on the farmer beyond the cost of proper disposal of the weed seed to avoid worsening field infestation. Fortunately, sicklepod seed also contains substantial amounts of carbohydrates and proteins. These edible components when freed from anthraquinones have a market in pet food as well as potential in human foods because of the high galactomannan ratio of the polysaccharides. Sicklepod seed was dehulled, and the ground endosperm was defatted, followed by sequential solvent extraction of the defatted seed meal to isolate the anthraquinones, carbohydrates, and protein components into their respective classes. Each class of isolate was spectroscopically identified.

Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

PubMed

Young, Patricia A; Morrison, Sherie L; Timmerman, John M

2014-10-01

The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

Therapy Insight: preserving fertility in cyclophosphamide-treated patients with rheumatic disease.

PubMed

Dooley, Mary Anne; Nair, Raj

2008-05-01

Cyclophosphamide remains a necessary treatment for severe rheumatic diseases, despite the continued search for alternative therapies with less gonadal toxicity. The risk of premature gonadal failure and sterility might lead young patients to delay treatment with cyclophosphamide. The patient's age at treatment and the cumulative dose received remain important risk factors for cyclophosphamide-induced gonadal failure in both males and females. Estrogen-containing oral contraceptives for females and testosterone for males are suggested to reduce the gonadal toxicity of cyclophosphamide, although few studies support these interventions. Owing to increased side effects, hormonal therapy is often avoided in patients with edema, hypertension, nephrotic syndrome or antiphospholipid antibodies. Agonists and antagonists of gonadotropin receptors are under study. Gonadotropin-receptor agonists might have beneficial effects in addition to suppression of sex-hormone production. The outcome of attempted cryopreservation of eggs, embryos or ovaries remains uncertain for women seeking to preserve their reproductive potential. Storing male gametes before chemotherapy is widely practiced and technically successful. As recovery of menses or production of testosterone does not predict individual fertility, identification of biomarkers of gonadal function and reserve, including serum levels of several hormones, ultrasonographic measurements of ovarian volume and antral follicle count, are necessary.

Effect of poly-α, γ, L-glutamic acid as a capping agent on morphology and oxidative stress-dependent toxicity of silver nanoparticles

PubMed Central

Stevanović, Magdalena; Kovačević, Branimir; Petković, Jana; Filipič, Metka; Uskoković, Dragan

2011-01-01

Highly stable dispersions of nanosized silver particles were synthesized using a straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was utilized as a reducing agent and poly-α, γ, L-glutamic acid (PGA), a naturally occurring anionic polymer, was used as a capping agent to protect the silver nanoparticles from agglomeration and render them biocompatible. Use of ammonia during synthesis was avoided. Our study clearly demonstrates how the concentration of the capping agent plays a major role in determining the dimensions, morphology, and stability, as well as toxicity of a silver colloidal solution. Hence, proper optimization is necessary to develop silver colloids of narrow size distribution. The samples were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurement. MTT assay results indicated good biocompatibility of the PGA-capped silver nanoparticles. Formation of intracellular reactive oxygen species was measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did not induce intracellular formation of reactive oxygen species. PMID:22131829

The chalcone derivative Chana 1 protects against amyloid β peptide-induced oxidative stress and cognitive impairment.

PubMed

Kwak, Jieun; Kim, Mi-Jeong; Choi, Kyung-Chul; Choi, Hyo-Kyung; Jun, Woojin; Park, Hyun-Jin; Lee, Yoo-Hyun; Yoon, Ho-Geun

2012-07-01

Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid β (Aβ)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. In this study, we investigated the effect of Chana 1 against Aβ-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana 1 in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against Aβ-induced neuronal cell death in PC12 cells. Oral administration of Chana 1 at a dose of 50 mg/kg body weight/day significantly improved Aβ-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

Stable Gene Targeting in Human Cells Using Single-Strand Oligonucleotides with Modified Bases

PubMed Central

Rios, Xavier; Briggs, Adrian W.; Christodoulou, Danos; Gorham, Josh M.; Seidman, Jonathan G.; Church, George M.

2012-01-01

Recent advances allow multiplexed genome engineering in E. coli, employing easily designed oligonucleotides to edit multiple loci simultaneously. A similar technology in human cells would greatly expedite functional genomics, both by enhancing our ability to test how individual variants such as single nucleotide polymorphisms (SNPs) are related to specific phenotypes, and potentially allowing simultaneous mutation of multiple loci. However, oligo-mediated targeting of human cells is currently limited by low targeting efficiencies and low survival of modified cells. Using a HeLa-based EGFP-rescue reporter system we show that use of modified base analogs can increase targeting efficiency, in part by avoiding the mismatch repair machinery. We investigate the effects of oligonucleotide toxicity and find a strong correlation between the number of phosphorothioate bonds and toxicity. Stably EGFP-corrected cells were generated at a frequency of ~0.05% with an optimized oligonucleotide design combining modified bases and reduced number of phosphorothioate bonds. We provide evidence from comparative RNA-seq analysis suggesting cellular immunity induced by the oligonucleotides might contribute to the low viability of oligo-corrected cells. Further optimization of this method should allow rapid and scalable genome engineering in human cells. PMID:22615794

Dose escalation methods in phase I cancer clinical trials.

PubMed

Le Tourneau, Christophe; Lee, J Jack; Siu, Lillian L

2009-05-20

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.

Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies.

PubMed

Avila, Jesús; Pallas, Noemí; Bolós, Marta; Sayas, C Laura; Hernandez, Felix

2016-06-01

Microtubule associated protein tau, a protein mainly expressed in neurons, plays an important role in several diseases related to dementia, named tauopathies. Alzheimer disease is the most relevant tauopathy. The role of tau protein in dementia is now a topic under discussion, and is the focus of this review. We have covered two major areas: tau pathology and tau as a therapeutic target. Tau pathology is mainly related to a gain of toxic function due to an abnormal accumulation, aberrant modifications (such as hyperphosphorylation and truncation, among others) and self-aggregation of tau into oligomers or larger structures. Also, tau can be found extracellularly in a toxic form. Tau-based therapy is mainly centered on avoiding the gain of these toxic functions of tau. Tau therapies are focused on lowering tau levels, mainly of modified tau species that could be toxic for neurons (phosphorylated, truncated or aggregated tau), in intracellular or extracellular form. Decreasing the levels of those toxic species is a possible therapeutic strategy.

Lead toxicity as an etiology for abdominal pain in the emergency department.

PubMed

Moriarity, Risa S; Harris, James T; Cox, Robert D

2014-02-01

Abdominal pain is an uncommon presentation of lead toxicity in the emergency department (ED). However, making the diagnosis is important in avoiding unnecessary testing and the long-term sequelae of lead toxicity. To illustrate possible presentations of abdominal pain secondary to lead toxicity and highlight the importance of taking a thorough patient history. We report 2 patients who presented to the ED with abdominal pain and underwent extensive evaluations that did not reveal an etiology. At follow-up visits, their occupational histories revealed possible lead exposures from working for a bullet-recycling company. Tests revealed that each patient had extremely high lead levels and they were both treated for lead toxicity. Their abdominal pain resolved as their lead levels decreased. These cases demonstrate a rare but significant cause of abdominal pain in the ED. Although history-taking in the ED is necessarily brief, these cases underscore the importance of obtaining an occupational history. Copyright © 2014 Elsevier Inc. All rights reserved.

[Pharmacogenomics in neuro-oncology].

PubMed

Riese-Jorda, H H; Baez, J M

Chemotherapy protocols for treatment of brain tumors use toxic molecules for killing cancer cells in a similar way that protocols for treating other cancers. Therefore, secondary effects and poor response are the major handicaps. Technological developments based on pharmacogenomics and pharmacoproteomics will predict response and toxicity giving rise to a personalized medicine. However, there are only few studies that correlate chemotherapeutical molecules for brain tumor treatment and prediction of response and toxicity. The development of new technologies based on high-density microarrays allows the progressive identification of genes whose presence will predict the efficacy of therapeutic protocols. Once identified, specific equipments based on low-density arrays will detect exclusively in an easy and fast way the presence of genes in order to predict patient's response and avoid toxicity. Other more sophisticated techniques at present still at an experimental step based on proteomics as MALDI (Matrix-Assisted Laser Desorption Ionization) and SELDI (Surface-Enhanced Laser Desorption Ionization) will allow the identification of proteins that could predict response and toxicity.

[Household gas poisonings].

PubMed

Maloca, Ivana; Macan, Jelena; Varnai, Veda Marija; Turk, Rajka

2006-12-01

Exposure to toxic gases which can induce serious health effects, can occur in the working as well as in general environment, including home. The severity of gas poisoning is determined by its physical and chemical characteristics, intensity and duration of exposure, and concomitant diseases and injuries in the poisoned person. Manifestations of gas toxic action involve simple asphyxia, local irritation of respiratory mucosa, systemic toxicity, and a combination of these mechanisms. This article describes the characteristics, modes of exposure and health effects of most common gases causing poisoning at home. These include gas fuels, carbon monoxide, ammonia, chlorine, and fire gases such as nitrogen and sulphur oxides, hydrogen cyanide and phosgene. First aid as well as preventive measures to avoid exposure to toxic gases and prevent fire at home are also given. The Croatian Poison Control Centre gathered data on toxic gas exposures in households between November 2005 and July 2006. During this period 30 persons (3 % of the total number of cases) were exposed to toxic gases at home, including carbon monoxide, irritating vapours from cleaning agents and disinfectants, gas fuels, septic tank gases, tear-gas, and chlorofluorocarbons from refrigerators.

Potential fluoride toxicity from oral medicaments: A review.

PubMed

Ullah, Rizwan; Zafar, Muhammad Sohail; Shahani, Nazish

2017-08-01

The beneficial effects of fluoride on human oral health are well studied. There are numerous studies demonstrating that a small amount of fluoride delivered to the oral cavity decreases the prevalence of dental decay and results in stronger teeth and bones. However, ingestion of fluoride more than the recommended limit leads to toxicity and adverse effects. In order to update our understanding of fluoride and its potential toxicity, we have described the mechanisms of fluoride metabolism, toxic effects, and management of fluoride toxicity. The main aim of this review is to highlight the potential adverse effects of fluoride overdose and poorly understood toxicity. In addition, the related clinical significance of fluoride overdose and toxicity has been discussed.

Chitosan-Acrylic Polymeric Nanoparticles with Dynamic Covalent Bonds. Synthesis and Stimuli Behavior.

PubMed

Palacio, Herman; Otálvaro, Felipe; Giraldo, Luis Fernando; Ponchel, Gilles; Segura-Sánchez, Freimar

2017-12-01

Drug delivery represents one of the most important research fields within the pharmaceutical industry. Different strategies are reported every day in a dynamic search for carriers with the ability to transport drugs across the body, avoiding or decreasing toxic issues and improving therapeutic activity. One of the most interesting strategies currently under research is the development of drug delivery systems sensitive to different stimuli, due to the high potential attributed to the selective delivery of the payload. In this work, a stimuli-sensitive nanocarrier was built with a bifunctional acrylic polymer, linked by imine and disulfide bonds to thiolate chitosan, the latter being a biopolymer widely known in the field of tissue engineering and drug delivery by its biodegradability and biocompatibility. These polymer nanoparticles were exposed to different changes in pH and redox potential, which are environments commonly found inside cancer cells. The results proof the ability of the nanoparticles to keep the original structure when either changes in pH or redox potential were applied individually. However, when both stimuli were applied simultaneously, a disassembly of the nanoparticles was evident. These special characteristics make these nanoparticles suitable nanocarriers with potential for the selective delivery of anticancer drugs.

Photoenhanced toxicity of weathered oil to Mysidopsis bahia

USGS Publications Warehouse

Cleveland, L.; Little, E.E.; Calfee, R.D.; Barron, M.G.

2000-01-01

The toxicity of a water-accommodated fraction (WAF) prepared from weathered oil was assessed in a 7-day static renewal test with Mysidopsis bahia. Weathered oil was collected from the 5 x monitoring well at the Guadalupe oil field. Solar ultraviolet and visible light intensities were measured in various habitats in the vicinity of the weathered oil sample collection site, and the resultant measurements were used to produce laboratory light treatments that were representative of the on-site quality and intensity of natural solar radiation. Each of five WAF dilutions and a control without WAF was tested under three different simulated solar radiation intensities. During the test, survival and growth of the mysids, irradiance, and total petroleum hydrocarbon (TPH) concentrations in the test treatments were measured. Significant increases (P ??? 0.05) in mortality occurred among mysids exposed to 0.57 and 1.30 mg TPH/l and the effects were potentiated as irradiance increased. Seven-day LC50 (0.92-0.42 mg TPH/l) and LC20 (0.58-0.15 mg TPH/l) values decreased as the simulated solar irradiance increased. Calculated EC20 and EC50 values for mysid growth indicate that surviving mysids exposed to 0.1-1.0 mg TPH/l would incur significant reductions (P ??? 0.05) in productivity (biomass). Results of the present study indicate that effects elicited through the interaction of WAF of weathered oil and solar radiation will substantially increase the toxicity of weathered oil. Further, the photomediated effects of petroleum compounds measured as TPH on mysid survival and growth demonstrate a need to consider the interactions of ultraviolet light and contaminant to avoid under estimating toxicity that might occur in the environment. (C) 2000 Elsevier Science B.V.

Prophylaxis with human serum butyrylcholinesterase protects Göttingen minipigs exposed to a lethal high-dose of sarin vapor.

PubMed

Saxena, Ashima; Hastings, Nicholas B; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

2015-08-05

Serum-derived human butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a potential prophylactic nerve agent countermeasure. Previously, we reported the prophylactic efficacy of Hu BChE in Göttingen minipigs against a whole-body exposure to 4.1mg/m(3) of sarin (GB) vapor, which produced lethality over 60min. Since the toxicity of nerve agent is concentration-dependent, in the present study, we investigated the toxic effects of an almost 3-fold higher rate of GB vapor exposure and the ability of Hu BChE to protect minipigs against this exposure. Male minipigs were subjected to: (1) air exposure; (2) GB vapor exposure; or (3) pretreatment with 7.5mg/kg of Hu BChE by i.m. injection, 24h prior to whole-body exposure to 11.4mg/m(3) of GB vapor for 10min. Electrocardiogram, electroencephalogram, and pupil size were monitored throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB bound to red blood cells and plasma. A novel finding was that saline-treated animals exposed to GB vapor did not develop any seizures, but manifested a variety of cardiac and whole blood toxic signs and rapidly died due to respiratory failure. Strikingly, pre-treatment with 7.5mg/kg of Hu BChE not only prevented lethality, but also avoided all cardiac toxic signs manifested in the non-treated cohort. Thus, Hu BChE alone can serve as an effective prophylactic countermeasure versus a lethal high-dose exposure to GB vapor. Published by Elsevier Ireland Ltd.

The preservation of living cells with biocompatible microparticles

NASA Astrophysics Data System (ADS)

Yang, Jing; Zhu, Yingnan; Xu, Tong; Pan, Chao; Cai, Nana; Huang, He; Zhang, Lei

2016-07-01

Biomedical applications of living cells have rapidly expanded in many fields such as toxic detection, drug screening, and regenerative medicine, etc. Efficient methods to support cell survival and maintain activity in vitro have become increasingly important. However, traditional cryopreservation for living cell-based applications is limited by several problems. Here, we report that magnetic hydrogel microparticles can physically assemble into a 3D environment for efficient cell preservation in physiological conditions, avoiding any chemical reactions that would damage the cells. Two representative cell lines (loosely and firmly adherent) were tested to evaluate the versatility of this method. The results showed that cell longevity was significantly extended to at least 15 days, while the control cell samples without microparticles quickly died within 3 days. Moreover, after preservation, cells can be easily retrieved by applying a magnet to separate the magnetic particles. This strategy can also inhibit cell over-proliferation while avoiding the use of temperature extremes or toxic cryoprotectants that are essential in cryopreservation.

Can Batesian mimicry help plants to deter herbivores?

PubMed

Massei, Giovanna; Cotterill, Jane V; Coats, Julia C; Bryning, Gareth; Cowan, Dave P

2007-06-01

Several authors have suggested that edible plants could avoid herbivory by mimicking olfactory cues of toxic plants. However, very few studies have been carried out to test this hypothesis. The aims of the present study were to identify the volatiles of three clover species and to test whether a species lacking chemical defences, such as red clover, could avoid being grazed by rabbits by mimicking the volatiles of the cyanogenic white clover. Two main volatiles were identified in all three clover species, and a further two volatiles were present in white clover only. Rabbits presented with a choice between white clover, red clover and red clover sprayed with white clover extract ate significantly more red clover than white or white-flavoured red clover. The results suggest that the volatiles of toxic plants could be used and exploited as a source of natural, safe and effective repellents to control the impact of pest herbivores on plants. Copyright 2007 Society of Chemical Industry.

Exploring the Impact of Toxic Attitudes and a Toxic Environment on the Veterinary Healthcare Team

PubMed Central

Moore, Irene C.; Coe, Jason B.; Adams, Cindy L.; Conlon, Peter D.; Sargeant, Jan M.

2015-01-01

The objective of this qualitative study was to compare veterinarians’ and Registered Veterinary Technicians’ (RVT’s) perceptions of the veterinary healthcare team with respect to the impact of toxic attitudes and a toxic environment. Focus group interviews using a semi-structured interview guide and follow up probes were held with four veterinarian groups (23 companion animal veterinarians) and four Registered Veterinary Technician groups (26 RVTs). Thematic analysis of the discussions indicated both veterinarian and RVT participants felt team members with manifestations of toxic attitudes negatively impacted veterinary team function. These manifestations included people being disrespectful, being resistant to change, always wanting to be the “go to person,” avoiding conflict, and lacking motivation. When conflict was ignored, or when people with toxic attitudes were not addressed, a toxic environment often resulted. A toxic environment sometimes manifested when “broken communication and tension between staff members” occurred as a result of employees lacking confidence, skills, or knowledge not being managed properly. It also occurred when employees did not feel appreciated, when there was difficulty coping with turnover, and when there were conflicting demands. The presence of people manifesting a toxic attitude was a source of frustration for both veterinarian and RVT participants. Prompt and consistent attention to negative behaviors is recommended to reduce the development of a toxic environment. PMID:26779492

ADDME – Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective

PubMed Central

Tsaioun, Katya; Bottlaender, Michel; Mabondzo, Aloise

2009-01-01

The advent of early absorption, distribution, metabolism, excretion, and toxicity (ADMET) screening has increased the attrition rate of weak drug candidates early in the drug-discovery process, and decreased the proportion of compounds failing in clinical trials for ADMET reasons. This paper reviews the history of ADMET screening and its place in pharmaceutical development, and central nervous system drug discovery in particular. Assays that have been developed in response to specific needs and improvements in technology that result in higher throughput and greater accuracy of prediction of human mechanisms of absorption and toxicity are discussed. The paper concludes with the authors' forecast of new models that will better predict human efficacy and toxicity. PMID:19534730

The weaker points of fish acute toxicity tests and how tests on embryos can solve some issues.

PubMed

Wedekind, Claus; von Siebenthal, Beat; Gingold, Ruth

2007-07-01

Fish acute toxicity tests play an important role in environmental risk assessment and hazard classification because they allow for first estimates of the relative toxicity of various chemicals in various species. However, such tests need to be carefully interpreted. Here we shortly summarize the main issues which are linked to the genetics and the condition of the test animals, the standardized test situations, the uncertainty about whether a given test species can be seen as representative to a given fish fauna, the often missing knowledge about possible interaction effects, especially with micropathogens, and statistical problems like small sample sizes and, in some cases, pseudoreplication. We suggest that multi-factorial embryo tests on ecologically relevant species solve many of these issues, and we shortly explain how such tests could be done to avoid the weaker points of fish acute toxicity tests.

Toxicity to and egg-laying avoidance of Drosophila suzukii (Diptera: Drosophilidae) caused by an old alternative inorganic insecticide preparation.

PubMed

Andreazza, Felipe; Vacacela Ajila, Henry E; Haddi, Khalid; Colares, Felipe; Pallini, Angelo; Oliveira, Eugênio E

2018-04-01

The application of synthetic insecticides remains the most used tool for the management of spotted-wing drosophila, Drosophila suzukii (Matsumura) (Diptera: Drosophilidae). However, management of this pest in the organic production of soft-skinned fruits is a complex task due to the restricted number of registered products. Here, we assess the toxicity of lime sulfur and evaluate whether lime sulfur-treated strawberry plants affected the oviposition and development of D. suzukii. Lime sulfur exhibited adequate toxicity to D. suzukii (LC 50 = 26.6 mL L -1 ) without phytotoxicity to strawberry plants. When D. suzukii females were exposed to lime sulfur-treated plants in no-choice bioassays, oviposition was significantly (t-test, P < 0.05) reduced compared with that on untreated plants. In free-choice bioassays, D. suzukii females laid significantly (paired t-test, P < 0.05) more eggs on untreated plants. Furthermore, in the free-choice bioassays, immature development was slower for adults that originated from eggs laid on lime sulfur-treated plants than from those laid on untreated plants. Lime sulfur showed adequate control and, therefore, has potential for use as a management tool against D. suzukii infestations in organic production systems. This old, alternative insecticide preparation not only caused adult fly mortality, but also reduced the number of eggs laid on lime sulfur-treated plants. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Prediction of the developmental toxicity hazard potential of halogenated drinking water disinfection by-products tested by the in vitro hydra assay

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

Fu, L.J.; Johnson, E.M.; Newman, L.M.

A series of seven randomly selected potential halogenated water disinfection by-products were evaluated in vitro by the hydra assay to determine their developmental toxicity hazard potential. For six of the chemicals tested by this assay (dibromoacetonitrile; trichloroacetonitrile; 2-chlorophenol; 2,4,6-trichlorophenol; trichloroacetic acid; dichloroacetone) it was predicted that they would be generally equally toxic to both adult and embryonic mammals when studied by means of standard developmental toxicity teratology tests. However, the potential water disinfection by-product chloroacetic acid (CA) was determined to be over eight times more toxic to the embryonic developmental portion of the assay than it was to the adults.more » Because of this potential selectivity, CA is a high-priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential and/or to establish a NOAEL by the route of most likely human exposure.« less

Serotonin syndrome: a complex but easily avoidable condition.

PubMed

Dvir, Yael; Smallwood, Patrick

2008-01-01

Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivity -- tremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivity -- diaphoresis, fever, tachycardia and tachypnea; (c) altered mental status -- agitation, excitement and, in advanced stages, confusion (Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434-441). It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors (Houlihan D. Serotonin syndrome resulting from coadministration of tramodol, venlafaxine, and mirtazapine. Ann Pharmacother 2004;38:411-413). The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120). Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. The following case highlights the complex nature in which serotonin syndrome can arise, as well as the proper recognition and treatment of a potentially life-threatening yet easily avoidable condition.

Susceptibility of Caenorhabditis elegans to Burkholderia Infection Depends on Prior Diet and Secreted Bacterial Attractants

PubMed Central

Cooper, Vaughn S.; Carlson, Wendy A.; LiPuma, John J.

2009-01-01

The nematode Caenorhabditis elegans may be killed by certain pathogenic bacteria and thus is a model organism for studying interactions between bacteria and animal hosts. However, growing nematodes on prey bacteria may influence their susceptibility to potential pathogens. A method of axenic nematode culture was developed to isolate and quantify interactions between C. elegans and potentially pathogenic strains of the Burkholderia cepacia complex. Studying these dynamics in liquid solution rather than on agar surfaces minimized nematode avoidance behavior and resolved more differences among isolates. Most isolates of B. cenocepacia, B. ambifaria and B. cepacia caused 60–80% mortality of nematodes after 7 days, whereas isolates of B. multivorans caused less mortality (<25%) and supported nematode reproduction. However, some B. cenocepacia isolates recovered from chronic infections were much less virulent (5–28% mortality). As predicted, prior diet altered the outcome of interactions between nematodes and bacteria. When given the choice between Burkholderia and E. coli as prey on agar, axenically raised nematodes initially preferred most lethal Burkholderia isolates to E. coli as a food source, but this was not the case for nematodes fed E. coli, which avoided toxic Burkholderia. This food preference was associated with the cell-free supernatant and thus secreted compounds likely mediated bacterial-nematode interactions. This model, which isolates interactions between bacteria and nematodes from the effects of prior feeding, demonstrates that bacteria can influence nematode behavior and their susceptibility to pathogens. PMID:19956737

Temporal aspects of copper homeostasis and its crosstalk with hormones

PubMed Central

Peñarrubia, Lola; Romero, Paco; Carrió-Seguí, Angela; Andrés-Bordería, Amparo; Moreno, Joaquín; Sanz, Amparo

2015-01-01

To cope with the dual nature of copper as being essential and toxic for cells, plants temporarily adapt the expression of copper homeostasis components to assure its delivery to cuproproteins while avoiding the interference of potential oxidative damage derived from both copper uptake and photosynthetic reactions during light hours. The circadian clock participates in the temporal organization of coordination of plant nutrition adapting metabolic responses to the daily oscillations. This timely control improves plant fitness and reproduction and holds biotechnological potential to drive increased crop yields. Hormonal pathways, including those of abscisic acid, gibberellins, ethylene, auxins, and jasmonates are also under direct clock and light control, both in mono and dicotyledons. In this review, we focus on copper transport in Arabidopsis thaliana and Oryza sativa and the presumable role of hormones in metal homeostasis matching nutrient availability to growth requirements and preventing metal toxicity. The presence of putative hormone-dependent regulatory elements in the promoters of copper transporters genes suggests hormonal regulation to match special copper requirements during plant development. Spatial and temporal processes that can be affected by hormones include the regulation of copper uptake into roots, intracellular trafficking and compartmentalization, and long-distance transport to developing vegetative and reproductive tissues. In turn, hormone biosynthesis and signaling are also influenced by copper availability, which suggests reciprocal regulation subjected to temporal control by the central oscillator of the circadian clock. This transcriptional regulatory network, coordinates environmental and hormonal signaling with developmental pathways to allow enhanced micronutrient acquisition efficiency. PMID:25941529

Establishment of a bioassay for the toxicity evaluation and quality control of Aconitum herbs.

PubMed

Qin, Yi; Wang, Jia-bo; Zhao, Yan-ling; Shan, Li-mei; Li, Bao-cai; Fang, Fang; Jin, Cheng; Xiao, Xiao-he

2012-01-15

Currently, no bioassay is available for evaluating the toxicity of Aconitum herbs, which are well known for their lethal cardiotoxicity and neurotoxicity. In this study, we established a bioassay to evaluate the toxicity of Aconitum herbs. Test sample and standard solutions were administered to rats by intravenous infusion to determine their minimum lethal doses (MLD). Toxic potency was calculated by comparing the MLD. The experimental conditions of the method were optimized and standardized to ensure the precision and reliability of the bioassay. The application of the standardized bioassay was then tested by analyzing 18 samples of Aconitum herbs. Additionally, three major toxic alkaloids (aconitine, mesaconitine, and hypaconitine) in Aconitum herbs were analyzed using a liquid chromatographic method, which is the current method of choice for evaluating the toxicity of Aconitum herbs. We found that for all Aconitum herbs, the total toxicity of the extract was greater than the toxicity of the three alkaloids. Therefore, these three alkaloids failed to account for the total toxicity of Aconitum herbs. Compared with individual chemical analysis methods, the chief advantage of the bioassay is that it characterizes the total toxicity of Aconitum herbs. An incorrect toxicity evaluation caused by quantitative analysis of the three alkaloids might be effectively avoided by performing this bioassay. This study revealed that the bioassay is a powerful method for the safety assessment of Aconitum herbs. Copyright © 2011 Elsevier B.V. All rights reserved.

A categorical structure-activity relationship analysis of the developmental toxicity of antithyroid drugs.

PubMed

Cunningham, Albert R; Carrasquer, C Alex; Mattison, Donald R

2009-01-01

The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action.

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

PubMed Central

Fan, Cathy Q.; Crawford, James M.

2014-01-01

Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules. Contributing factors are SEC glutathione depletion, nitric oxide depletion, increased intrahepatic expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially critical condition of these patients, transjugular biopsy may be the preferred route for liver biopsy to exclude other potential causes of liver dysfunction and to establish a diagnosis of SOS. Treatment includes rigorous fluid management so as to avoid excessive fluid overload while avoiding too rapid diuresis or pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic agents, or methylprednisolone, and liver transplantation. Proposed strategies for prevention and prophylaxis include reduced-intensity conditioning radiation for HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with oxaliplatin-based chemotherapeutic regimes. While significant progress has been made in understanding the pathogenesis of SOS and in mitigating against its adverse outcomes, this condition remains a serious complication of a selective group of medical treatments. PMID:25755580

Gallium-67-citrate uptake in a case of acne vulgaris

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

Kipper, M.S.; Taylor, A.; Ashburn, W.L.

1981-09-01

A case of increased Ga-67 uptake in a patient with active acne vulgaris is reported. The scan was requested in a search for metastatic testicular carcinoma or bleomycin pulmonary toxicity. Careful clinical evaluation including physical examination was necessary in order to avoid an erroneous scan interpretation.

Release and toxicity comparison between industrial- and sunscreen-derived nano-ZnO particles

EPA Science Inventory

Many consumer products containing ZnO have raised concern for safety in regards toenvironmental impact and the public health. Widely used sunscreens for protectingagainst UV and avoiding sunburns represent a great exposure to nano-ZnO, one of theingredients commonly applied in su...

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks.

PubMed

Maurya, Sushil K; Rana, Rohit

2017-01-01

An efficient, eco-compatible diversity-oriented synthesis (DOS) approach for the generation of library of sugar embedded macrocyclic compounds with various ring size containing 1,2,3-triazole has been developed. This concise strategy involves the iterative use of readily available sugar-derived alkyne/azide-alkene building blocks coupled through copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction followed by pairing of the linear cyclo-adduct using greener reaction conditions. The eco-compatibility, mild reaction conditions, greener solvents, easy purification and avoidance of hazards and toxic solvents are advantages of this protocol to access this important structural class. The diversity of the macrocycles synthesized (in total we have synthesized 13 macrocycles) using a set of standard reaction protocols demonstrate the potential of the new eco-compatible approach for the macrocyclic library generation.

Evaluation of benefits and risks associated with the agricultural use of organic wastes of pharmaceutical origin.

PubMed

Cucina, Mirko; Tacconi, Chiara; Ricci, Anna; Pezzolla, Daniela; Sordi, Simone; Zadra, Claudia; Gigliotti, Giovanni

2018-02-01

Industrial fermentations for the production of pharmaceuticals generate large volumes of wastewater that can be biologically treated to recover plant nutrients through the application of pharmaceutical-derived wastes to the soil. Nevertheless, benefits and risks associated with their recovery are still unexplored. Thus, the aim of the present work was to characterize three potential organic residues (sludge, anaerobic digestate and compost) derived from the wastewater generated by the daptomycin production process. The main parameters evaluated were the physico-chemical properties, potential contaminants (heavy metals, pathogens and daptomycin residues), organic matter stabilization and the potential toxicity towards soil microorganisms and plants. The results showed that all the studied materials were characterized by high concentrations of plant macronutrients (N, P and K), making them suitable for agricultural reuse. Heavy metal contents and pathogens were under the limits established by European and Italian legislations, avoiding the risk of soil contamination. The compost showed the highest organic matter stabilization within the studied materials, whereas the sludge and the anaerobic digestate were characterized by large amounts of labile organic compounds. Although the pharmaceutical-derived fertilizers did not negatively affect the soil microorganisms, as demonstrated by the enzymatic activities, the sludge and the anaerobic digestate caused a moderate and strong phytotoxicity, respectively. The compost showed no toxic effect towards plant development and, moreover, it positively affected the germination and growth in lettuce and barley. The results obtained in the present study demonstrate that the valorization of pharmaceutical-derived materials through composting permits their agricultural reuse and also represents a suitable strategy to move towards a zero-waste production process for daptomycin. Copyright © 2017 Elsevier B.V. All rights reserved.

Leaching assessments of toxic metals in waste plasma display panel glass.

PubMed

Chen, Mengjun; Jiang, Pengfei; Chen, Haiyan; Ogunseitan, Oladele A; Li, Yungui

2015-06-01

The plasma display panel (PDP) is rapidly becoming obsolete, contributing in large amounts to the electronic waste stream. In order to assess the potential for environmental pollution due to hazardous metals leached from PDP glass, standardized leaching procedures, chemical speciation assessments, and bioavailability tests were conducted. According to the Toxicity Characteristic Leaching Procedure (TCLP), arsenic in back glass was present at 4.46 ± 0.22 mg/L, close to its regulation limit of 5 mg/L. Zn is not available in the TCLP, but its TCLP leaching concentration in back glass is 102.96 ± 5.34 mg/L. This is because more than 90% of Zn is in the soluble and exchangeable and carbonate fraction. We did not detect significant levels of Ag, Ba, or Cu in the TCLP leachate, and the main fraction of Ag and Ba is residual, more than 95%, while the fraction distribution of Cu changes SEP by SEP. Ethylenediamine tetraacetic acid (EDTA)- and diethylenetriamine pentaacetic acid (DTPA)-extractable Ag, As, Ba, Cu, Zn, and Ni indicate a lower biohazards potential. These results show that, according to the EPA regulations, PDP glass may not be classified as hazardous waste because none of the metals exceeded their thresholds in PDP leachate. However, the concentrations of As and Zn should be lowered in the manufacturing process and finished product to avoid potential pollution problems. The plasma display panel is rapidly becoming obsolete because of the liquid crystal display. In this study, the leachability of heavy metals contained in the waste plasma display panel glass was first examined by standardized leaching tests, typical chemical speciation assessments, and bioavailability tests, providing fundamental data for waste PDP glass recovery, recycling, and reuse.

Detoxification of cancerogenic compounds by lactic acid bacteria strains.

PubMed

Lili, Zhao; Junyan, Wei; Hongfei, Zhao; Baoqing, Zhu; Bolin, Zhang

2017-10-20

Carcinogens in food are an important issue that threat people's health right now. Lactic acid bacteria (LAB) strains as well-known probiotics have shown numerous perspectives in being used as a good food additive to confront cancerogenic compounds in recent years. Some LAB strains can remove cancerogenic compounds from medium environment via direct physical binding and avoid re-pollution of poisonous secondary metabolites which are generated from degradation of cancerogenic compounds. This article presents a whole overview of the physical-binding of LAB strains to such common cancerogenic compounds existed in food and feed environments as mycotoxins, polycyclic aromatic hydrocarbons (PAHs), heterocyclic amines (HAs) and pthalic acid esters (PAEs).In most cases, summaries of these published researches show that the binding of LAB strains to cancerogenic compounds is a physical process. Binding sites generally take place in cell wall, and peptidoglycan from LAB cells is the chief binding site. The adsorption of lactic acid bacteria to cancerogenic compounds is strain-specific. Specially, the strains from the two genera Lactobacillus and Bifidobacterium show a better potential in binding cancerogenic compounds. Moreover, we firstly used molecular dynamic computer model as a highly potential tool to simulate the binding behavior of peptidoglycan from Lactobacillus acidophilus to DBP, one of pthalic acid esters with genetic toxicity. It was seen that the theoretical data were quite consistent with the experimental results in terms of the ability of this bacterium to bind DBP. Also, the toxicity reduction of cancerogenic compounds by LAB strains could be achieved either in gastrointestinal model or animal tests and clinical researches as well. In conclusion, carefully selected LAB strains should be a good solution as one of safety strategies to reduce potential risk of cancerogenic compounds from food-based products.

Mineral constituents profile of biochar derived from diversified waste biomasses: implications for agricultural applications.

PubMed

Zhao, Ling; Cao, Xinde; Wang, Qun; Yang, Fan; Xu, Shi

2013-01-01

The wide distribution and high heterogeneity of different elements in biochars derived from diverse feedstocks make it difficult to regulate their application in soil and to evaluate the maximum potential contribution of the nutrients and trace metals as well as the potential risk of toxic metals. This study classified 20 biochars, covering six typical categories, into three clusters according to their similarity and distance on nutrients and minerals using cluster analysis. Four principle components (PC) were extracted using factor analysis to reduce dimension and clearly characterize the mineral profile of these biochars. The contribution of each group of elements in the PCs to every cluster was clarified. PC1 had a high loading for Mg, Cu, Zn, Al, and Fe; PC2 was related to N, K, and Mn; and PC3 and PC4 mainly represented P and Ca. Cluster 1 included bone dregs and eggshell biochars with PC3 and PC4 as the main contributors. Cluster 2 included waterweeds and waste paper biochars, which were close to shrimp hull and chlorella biochars, with the main contributions being from PC2 and PC4. Cluster 3 included biochars with PC1 as the main contributor. At a soil biochar amendment rate of 50 t ha, the soil nutrients were significantly elevated, whereas the rise in toxic metals was negligible compared with Class I of the China Environmental Quality Standards for Soil. Biochar can potentially supply soil nutrients and trace metals, and different cluster biochars can be applied appropriately to different soils so that excessive or deficient nutrient and metal applications can be avoided. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Pre-treatment of Stegomyia aegypti mosquitoes with a sublethal dose of imidacloprid impairs behavioural avoidance induced by lemon oil and DEET.

PubMed

Thany, S H; Tong, F; Bloomquist, J R

2015-03-01

The present study was conducted to determine whether imidacloprid can impair the avoidance behaviour of the mosquito Stegomyia aegypti. Laboratory investigations using a T-maze apparatus showed that St. aegypti mosquitoes present long term avoidance behaviour when they are exposed to repetitive trials with lemon oil and DEET. The present study tested the effect of a sublethal dose of imidacloprid on the avoidance behaviour of St. aegypti mosquitoes over a 48 h period. Data suggest that 0.5 ng of imidacloprid/mosquito reduces the avoidance behaviour of mosquitoes exposed to lemon oil, on the first day of exposure, after the second trial; whereas imidacloprid affected DEET repellency only the first day of exposure, after the second trial. Imidacloprid was toxic against St. aegypti mosquitoes, and at sublethal doses was able to impair the repellency induced by lemon oil and DEET. The present data were consistent with the finding that St. aegypti mosquitoes exhibit long term avoidance behaviour, and treatment of mosquitoes with a sublethal dose of imidacloprid under DEET application can affect the repellency of DEET against St. aegypti. © 2014 The Royal Entomological Society.

Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity

PubMed Central

Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

2014-01-01

Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

Mild forms of toxic shock syndrome toxin-1-mediated exanthematous disease related to Staphylococcus aureus infection.

PubMed

Moriguchi, Naohiko; Kano, Tomowa; Yoshimatsu, Yutaka; Yanagida, Hidehiko

2016-08-01

The present report describes three patients with toxic shock syndrome toxin (TSST)-1-associated exanthematous disease. In all patients, fever and systemic erythema without hemodynamic disturbance occurred following cellulitis of the lower limbs. At the site of infection, TSST-1 producing Methicillin-susceptible Staphylococcus aureus was detected. They defervesced and erythema resolved in response to administration of an antimicrobial drug, thereby avoiding severe illness. These patients did not meet the criteria for a clinical diagnosis of toxic shock syndrome. Measurement of T-cell receptor Vβ2-positive T cells in the peripheral blood early after onset of symptoms was useful for diagnosis. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chloride: from Nutrient to Toxicant.

PubMed

Geilfus, Christoph-Martin

2018-05-01

In salinized soils in which chloride (Cl-) is the dominant salt anion, growth of plants that tolerate only low concentrations of salt (glycophytes) is disturbed by Cl- toxicity. Chlorotic discolorations precede necrotic lesions, causing yield reductions. Little is known about the effects of Cl- toxicity on these dysfunctions. A lack of understanding exists regarding (i) the molecular and physiological mechanisms that lead to Cl--induced damage and (ii) the adaptive aspects of induced tolerance to Cl- salinity. Here, mechanistic explanations for the Cl--induced stress responses are proposed and novel ideas and strategies by which glycophytic plants avoid the excessive accumulation of Cl- are reviewed. New experiments are suggested to test the proposed hypotheses. Cl- salinity constrains global food security and thus we urgently need more research into the causes and consequences of Cl- salinity.

Disentangling taste and toxicity in aposematic prey

PubMed Central

Holen, Øistein Haugsten

2013-01-01

Many predators quickly learn to avoid attacking aposematic prey. If the prey vary in toxicity, the predators may alternatively learn to capture and taste-sample prey carefully before ingesting or rejecting them (go-slow behaviour). An increase in prey toxicity is generally thought to decrease predation on prey populations. However, while prey with a higher toxin load are more harmful to ingest, they may also be easier to recognize and reject owing to greater distastefulness, which can facilitate a taste-sampling foraging strategy. Here, the classic diet model is used to study the separate effects of taste and toxicity on predator preferences. The taste-sampling process is modelled using signal detection theory. The model is applicable to automimicry and Batesian mimicry. It shows that when the defensive toxin is sufficiently distasteful, a mimicry complex may be less profitable to the predator and better protected against predation if the models are moderately toxic than if they are highly toxic. Moreover, taste mimicry can reduce the profitability of the mimicry complex and increase protection against predation. The results are discussed in relation to the selection pressures acting on prey defences and the evolution of mimicry. PMID:23256198

Disentangling taste and toxicity in aposematic prey.

PubMed

Holen, Øistein Haugsten

2013-02-22

Many predators quickly learn to avoid attacking aposematic prey. If the prey vary in toxicity, the predators may alternatively learn to capture and taste-sample prey carefully before ingesting or rejecting them (go-slow behaviour). An increase in prey toxicity is generally thought to decrease predation on prey populations. However, while prey with a higher toxin load are more harmful to ingest, they may also be easier to recognize and reject owing to greater distastefulness, which can facilitate a taste-sampling foraging strategy. Here, the classic diet model is used to study the separate effects of taste and toxicity on predator preferences. The taste-sampling process is modelled using signal detection theory. The model is applicable to automimicry and batesian mimicry. It shows that when the defensive toxin is sufficiently distasteful, a mimicry complex may be less profitable to the predator and better protected against predation if the models are moderately toxic than if they are highly toxic. Moreover, taste mimicry can reduce the profitability of the mimicry complex and increase protection against predation. The results are discussed in relation to the selection pressures acting on prey defences and the evolution of mimicry.

Experiential avoidance as a generalized psychological vulnerability: comparisons with coping and emotion regulation strategies.

PubMed

Kashdan, Todd B; Barrios, Velma; Forsyth, John P; Steger, Michael F

2006-09-01

Extending previous work, we conducted two studies concerning the toxic influences of experiential avoidance (EA) as a core mechanism in the development and maintenance of psychological distress, and disruption of pleasant, engaging, and spontaneous activity. Of particular interest was whether EA accounted for relationships between coping and emotion regulation strategies on anxiety-related pathology (Study 1) and psychological distress and hedonic functioning over the course of a 21-day monitoring period (Study 2). In Study 1, EA mediated the effects of maladaptive coping, emotional responses styles, and uncontrollability on anxiety-related distress (e.g., anxiety sensitivity, trait anxiety, suffocation fears, and body sensation fears). In Study 2, EA completely mediated the effects of two emotion regulation strategies (i.e., suppression and reappraisal) on daily negative and positive experiences and was associated with diminished daily positive affective experiences and healthy life appraisals, diminished frequency of positive events and more frequent negative life events, and greater negative affective experiences. The present data show that cognitive reappraisal, a primary process of traditional cognitive-behavior therapy, was much less predictive of the quality of psychological experiences and events in everyday life compared with EA. Further consideration of experiential avoidance as a generalized diathesis and toxic process will be useful in improving our understanding of the etiology, phenomenology, and treatment of anxiety conditions, general human suffering, and disruptions in hedonic capacity.

Liver transplantation from a deceased donor with β-thalassemia intermedia is not contraindicated: A case report.

PubMed

Gumus, Ersin; Abbasoglu, Osman; Tanyel, Cahit; Gumruk, Fatma; Ozen, Hasan; Yuce, Aysel

2017-05-01

The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with β-thalassemia intermedia. A patient, 6-year-old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver. Hepatocellular injury due to acute graft rejection might have contributed to elevated ferritin levels by causing release of stored iron from the hemosiderotic liver graft. Iron chelation and phlebotomy therapies were started simultaneously in the early postoperative period to avoid iron-related organ toxicity and transplant failure. Follow-up with monthly phlebotomies after discharge yielded a favorable outcome with normal transplant functions. Thalassemia intermedia patients can be candidates of liver donors to decrease pretransplant waitlist mortality. After transplantation of a hemosiderotic liver, it is important to monitor the recipient in terms of iron overload and toxicity. Early attempts to lower iron burden including chelation therapy and/or phlebotomy should be considered to avoid organ toxicity and transplant failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Laccase-syringaldehyde-mediated degradation of trace organic contaminants in an enzymatic membrane reactor: Removal efficiency and effluent toxicity.

PubMed

Nguyen, Luong N; van de Merwe, Jason P; Hai, Faisal I; Leusch, Frederic D L; Kang, Jinguo; Price, William E; Roddick, Felicity; Magram, Saleh F; Nghiem, Long D

2016-01-01

Redox-mediators such as syringaldehyde (SA) can improve laccase-catalyzed degradation of trace organic contaminants (TrOCs) but may increase effluent toxicity. The degradation performance of 14 phenolic and 17 non-phenolic TrOCs by a continuous flow enzymatic membrane reactor (EMR) at different TrOC and SA loadings was assessed. A specific emphasis was placed on the investigation of the toxicity of the enzyme (laccase), SA, TrOCs and the treated effluent. Batch tests demonstrated significant individual and interactive toxicity of the laccase and SA preparations. Reduced removal of resistant TrOCs by the EMR was observed for dosages over 50μg/L. SA addition at a concentration of 10μM significantly improved TrOC removal, but no removal improvement was observed at the elevated SA concentrations of 50 and 100μM. The treated effluent showed significant toxicity at SA concentrations beyond 10μM, providing further evidence that higher dosage of SA must be avoided. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reducing impacts from ammunitions: A comparative life-cycle assessment of four types of 9mm ammunitions.

PubMed

Ferreira, Carlos; Ribeiro, José; Almada, Sara; Rotariu, Traian; Freire, Fausto

2016-10-01

Increase of environmental awareness of the population has pressured research activities in the defence area to cover environment and toxicity issues, where have been considered appropriate manners to reduce the environmental and toxicological impacts of ammunition. One of the adopted approaches to achieve such goal involves the replacement of lead and other heavy metals by alternative materials. However, the consequences of using alternative materials in ammunitions manufacturing are uncertain for the other life-cycle phases and trade-offs can occur. The present paper describes the potential benefits from the replacement of lead in the primer and in the projectile of a 9mm calibre ammunition. For that purpose, it is assessed and compared the environmental and toxicological impacts associated with the life-cycle of four ammunitions: combination of two types of projectiles (steel jacket and lead core; copper and nylon composite) with two types of primers (lead primer; non-lead primer). In addition, some potential improvements for the environmental performance of small calibre ammunition are also presented. To assess the impacts two Life-Cycle Impact Assessment methods are applied: CML for six environmental categories and USEtox to three toxicity categories. Results showed that the conclusion drawn for environmental and toxicological impact categories are distinct. In fact, ammunition production phase presents higher impacts for the environmental categories, whilst the operation phase has a higher impact to the toxicity categories. The substitution of lead in the primer and in the projectile provides a suitable alternative from a toxicology perspective; however, the composite projectile still presents some environmental concerns. The conclusions drawn are important for the procurement (and design) of environmental responsible ammunitions, in order to avoid (or decrease) the impacts for their manufacture and the effects on human health (e.g. shooters) and ecosystems near shooting ranges or hunting areas. Copyright © 2016 Elsevier B.V. All rights reserved.

Yellow Oleander Seed, or "Codo de Fraile" (Thevetia spp.): A Review of Its Potential Toxicity as a Purported Weight-Loss Supplement.

PubMed

González-Stuart, Armando; Rivera, José O

2018-05-04

The Dietary Supplements and Health Education Act (DSHEA), passed by the United States Congress in October of 1994, defines herbal products as nutritional supplements, not medications. This opened the market for diverse products made from plants, including teas, extracts, essential oils, and syrups. Mexico and the United States share an extensive border, where diverse herbal products are available to the public without a medical prescription. Research undertaken in the neighboring cities of Ciudad Juarez, Mexico, and El Paso, Texas, USA, shows the use of herbs is higher in this border area compared to the rest of the United States. A portion of the population is still under the erroneous impression that "natural" products are completely safe to use and therefore lack side effects. We review the dangers of ingesting the toxic seed of Thevetia spp. (family Apocynaceae), commonly known as "yellow oleander" or "codo de fraile," misleadingly advertised on the Internet as an effective and safe dietary supplement for weight loss. Lack of proper quality control regarding herbs generates a great variability in the quantity and quality of the products' content. Herb-drug interactions occur between some herbal products and certain prescription pharmaceuticals. Certain herbs recently introduced into the U.S. market may not have been previously tested adequately for purity, safety, and efficacy. Due to the lack of reliable clinical data regarding the safe use of various herbal products currently available, the public should be made aware regarding the possible health hazards of using certain herbs for therapeutic purposes. The potentially fatal toxicity of yellow oleander seed is confirmed by cases reported from various countries, while the purported benefits of using it for weight loss have not been evaluated by any known clinical trials. For this reason, the use of yellow oleander seed as a dietary supplement should be avoided.

Home composting as an alternative treatment option for organic household waste in Denmark: An environmental assessment using life cycle assessment-modelling

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

Andersen, J.K.; Boldrin, A.; Christensen, T.H.

2012-01-15

An environmental assessment of the management of organic household waste (OHW) was performed from a life cycle perspective by means of the waste-life cycle assessment (LCA) model EASEWASTE. The focus was on home composting of OHW in Denmark and six different home composting units (with different input and different mixing frequencies) were modelled. In addition, incineration and landfilling was modelled as alternatives to home composting. The most important processes contributing to the environmental impact of home composting were identified as greenhouse gas (GHG) emissions (load) and the avoided emissions in relation to the substitution of fertiliser and peat when compostmore » was used in hobby gardening (saving). The replacement of fertiliser and peat was also identified as one of the most sensible parameters, which could potentially have a significant environmental benefit. Many of the impact categories (especially human toxicity via water (HTw) and soil (HTs)) were affected by the heavy metal contents of the incoming OHW. The concentrations of heavy metals in the compost were below the threshold values for compost used on land and were thus not considered to constitute a problem. The GHG emissions were, on the other hand, dependent on the management of the composting units. The frequently mixed composting units had the highest GHG emissions. The environmental profiles of the home composting scenarios were in the order of -2 to 16 milli person equivalents (mPE) Mg{sup -1} wet waste (ww) for the non-toxic categories and -0.9 to 28 mPE Mg{sup -1} ww for the toxic categories. Home composting performed better than or as good as incineration and landfilling in several of the potential impact categories. One exception was the global warming (GW) category, in which incineration performed better due to the substitution of heat and electricity based on fossil fuels.« less

Olfactory toxicity in fishes.

PubMed

Tierney, Keith B; Baldwin, David H; Hara, Toshiaki J; Ross, Peter S; Scholz, Nathaniel L; Kennedy, Christopher J

2010-01-21

Olfaction conveys critical environmental information to fishes, enabling activities such as mating, locating food, discriminating kin, avoiding predators and homing. All of these behaviors can be impaired or lost as a result of exposure to toxic contaminants in surface waters. Historically, teleost olfaction studies have focused on behavioral responses to anthropogenic contaminants (e.g., avoidance). More recently, there has been a shift towards understanding the underlying mechanisms and functional significance of contaminant-mediated changes in fish olfaction. This includes a consideration of how contaminants affect the olfactory nervous system and, by extension, the downstream physiological and behavioral processes that together comprise a normal response to naturally occurring stimuli (e.g., reproductive priming or releasing pheromones). Numerous studies spanning several species have shown that ecologically relevant exposures to common pollutants such as metals and pesticides can interfere with fish olfaction and disrupt life history processes that determine individual survival and reproductive success. This represents one of the pathways by which toxic chemicals in aquatic habitats may increasingly contribute to the decline and at-risk status of many commercially and ecologically important fish stocks. Despite our emerging understanding of the threats that pollution poses for chemical communication in aquatic communities, many research challenges remain. These include: (1) the determination of specific mechanisms of toxicity in the fish olfactory sensory epithelium; (2) an understanding of the impacts of complex chemical mixtures; (3) the capacity to assess olfactory toxicity in fish in situ; (4) the impacts of toxins on olfactory-mediated behaviors that are still poorly understood for many fish species; and (5) the connections between sublethal effects on individual fish and the long-term viability of wild populations. This review summarizes and integrates studies on fish olfaction-contaminant interactions, including metrics ranging from the molecular to the behavioral, and highlights directions for future research. 2009 Elsevier B.V. All rights reserved.

Summary report of bioassays for the city of Hollywood water plant membrane reject water as it mixed with WWTP effluent in an ocean outfall environment

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

Fergen, R.E.; Vinci, P.; Bloetscher, F.

1999-07-01

A special bioassay study was conducted to review the impact of the City of Hollywood's Membrane Softening Water Treatment Plant (WRP) reject water as it mixes with the City's Wastewater Treatment Plant (WWTP) effluent. Three sampling periods occurred during 1997. The purpose of this study was to determine potential toxicity of the WTP reject water, pre-chlorinated effluent, and combined effluent, and to demonstrate if the combined effluent was acceptable for ocean discharge on the basis of no potential toxicity. Effluent was acceptable for ocean discharge on the basis of no potential toxicity. Effluent samples were collected at six sampling points;more » three were in the plant, while the other three were along the outfall pipeline. Definitive, static renewal bioassay tests were performed using Mysidopsis bahia and Menidia beryllina as indicators of potential toxicity. The bioassay tests at 30% effluent concentration indicate that there is not potential toxicity for the pre-chlorinated WTP effluent, WTP reject water, dechlorinate combined effluent at the plant, and chlorinated combined effluent at Holland Park, the riser, and the terminus. The results indicate that the WTP reject water (100%) is not toxic to Menidia beryllina but was toxic to Mysidopsis bahia. When combined with the WWRP effluent, the reject water's impact on the potential toxicity of the commingled effluent was insignificant. All of the tests indicate the combined effluents are not toxic to the species tested at the 30% effluent level. Therefore, potential toxicity concerns were not demonstrated for this outfall discharge and did not prevent FDEP from issuing a permit to the City of Hollywood for the disposal of the combined effluent. Furthermore, these results, in combination with the previous results, indicated that individual bioassay testing for the reject water for regulatory compliance is not required.« less

The profound effect of harmful cyanobacterial blooms: From food-web and management perspectives.

PubMed

Šulčius, Sigitas; Montvydienė, Danguolė; Mazur-Marzec, Hanna; Kasperovičienė, Jūratė; Rulevičius, Rokas; Cibulskaitė, Živilė

2017-12-31

Sustainable and effective water management plans must have a reliable risk assessment strategies for harmful cyanobacterial blooms (HABs) that would enable timely decisions to be made, thus avoiding the trespassing of ecological thresholds, leading to the collapse of ecosystem structure and function. Such strategies are usually based on cyanobacterial biomass and/or on the monitoring of known toxins, which may, however, in many cases, under- or over-represent the actual toxicity of the HAB. Therefore, in this study, by the application of growth-inhibition assays using different bacteria, algae, zooplankton and fish species, we assessed the toxicological potential of two cyanobacterial blooms that differed in total cyanobacterial biomass, species composition and cyanopeptide profiles. We demonstrated that neither cyanobacterial community composition nor its relative abundance, nor indeed concentrations of known toxins reflected the potential risk of HAB based on growth-inhibition assays. We discuss our findings in the context of food-web dynamics and ecosystem management, and suggest that toxicological tests should constitute a key element in the routine monitoring of water bodies so as to prevent under-/over-estimation of potential HAB risk for both ecosystem and public health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Emergency Department Use in the US-Mexico Border Region and Violence in Mexico: Is There a Relationship?

PubMed

Geissler, Kimberley H; Holmes, George M

2015-01-01

This study assessed the association between homicide rates in northern Mexico and potentially avoidable use of emergency departments (ED) in the US-Mexico border region. The border region is largely rural and underserved, making the identification and correction of potential barriers to access crucial. We used secondary data from state inpatient and ED discharge databases for California and Arizona for 2005-2010. A retrospective observational analysis using generalized linear models was used to determine whether the probability that an ED encounter was potentially avoidable was associated with homicide rates in the nearest Mexican municipality. To conduct the analysis, the location of ED encounters were identified and matched with homicide rates in the nearest Mexican municipality and regional characteristics. The probability that an ED encounter was potentially avoidable was calculated using the Billings ED algorithm. We found that 77% of ED encounters were potentially avoidable, with a higher percentage in border counties. There was no statistically significant relationship between homicide rates and the probability that an ED encounter was for a potentially avoidable condition for the full analytic sample (n = 24,859,273) and the uninsured and underinsured in the sample (n = 11,700,123). A substantial majority of ED encounters in the US-Mexico border region were potentially avoidable. However, there was not a strong relationship between homicide rates in northern Mexico and the distribution of ED discharges in Arizona and California. Given the large percentage of potentially avoidable ED encounters and the ongoing violence in Mexico, continuing to monitor this relationship is important. © 2015 National Rural Health Association.

Complex mixtures of dissolved pesticides show potential aquatic toxicity in a synoptic study of Midwestern U.S. streams

USGS Publications Warehouse

Nowell, Lisa H.; Moran, Patrick W.; Schmidt, Travis S.; Norman, Julia E.; Nakagaki, Naomi; Shoda, Megan E.; Mahler, Barbara J.; Van Metre, Peter C.; Stone, Wesley W.; Sandstrom, Mark W.; Hladik, Michelle L.

2018-01-01

Aquatic organisms in streams are exposed to pesticide mixtures that vary in composition over time in response to changes in flow conditions, pesticide inputs to the stream, and pesticide fate and degradation within the stream. To characterize mixtures of dissolved-phase pesticides and degradates in Midwestern streams, a synoptic study was conducted at 100 streams during May–August 2013. In weekly water samples, 94 pesticides and 89 degradates were detected, with a median of 25 compounds detected per sample and 54 detected per site. In a screening-level assessment using aquatic-life benchmarks and the Pesticide Toxicity Index (PTI), potential effects on fish were unlikely in most streams. For invertebrates, potential chronic toxicity was predicted in 53% of streams, punctuated in 12% of streams by acutely toxic exposures. For aquatic plants, acute but likely reversible effects on biomass were predicted in 75% of streams, with potential longer-term effects on plant communities in 9% of streams. Relatively few pesticides in water—atrazine, acetochlor, metolachlor, imidacloprid, fipronil, organophosphate insecticides, and carbendazim—were predicted to be major contributors to potential toxicity. Agricultural streams had the highest potential for effects on plants, especially in May–June, corresponding to high spring-flush herbicide concentrations. Urban streams had higher detection frequencies and concentrations of insecticides and most fungicides than in agricultural streams, and higher potential for invertebrate toxicity, which peaked during July–August. Toxicity-screening predictions for invertebrates were supported by quantile regressions showing significant associations for the Benthic Invertebrate-PTI and imidacloprid concentrations with invertebrate community metrics for MSQA streams, and by mesocosm toxicity testing with imidacloprid showing effects on invertebrate communities at environmentally relevant concentrations. This study documents the most complex pesticide mixtures yet reported in discrete water samples in the U.S. and, using multiple lines of evidence, predicts that pesticides were potentially toxic to nontarget aquatic life in about half of the sampled streams.

Validating potential toxicity assays to assess petroleum hydrocarbon toxicity in polar soil.

PubMed

Harvey, Alexis Nadine; Snape, Ian; Siciliano, Steven Douglas

2012-02-01

Potential microbial activities are commonly used to assess soil toxicity of petroleum hydrocarbons (PHC) and are assumed to be a surrogate for microbial activity within the soil ecosystem. However, this assumption needs to be evaluated for frozen soil, in which microbial activity is limited by liquid water (θ(liquid)). Influence of θ(liquid) on in situ toxicity was evaluated and compared to the toxicity endpoints of potential microbial activities using soil from an aged diesel fuel spill at Casey Station, East Antarctica. To determine in situ toxicity, gross mineralization and nitrification rates were determined by the stable isotope dilution technique. Petroleum hydrocarbon-contaminated soil (0-8,000 mg kg(-1)), packed at bulk densities of 1.4, 1.7, and 2.0 g cm(-3) to manipulate liquid water content, was incubated at -5°C for one, two, and three months. Although θ(liquid) did not have a significant effect on gross mineralization or nitrification, gross nitrification was sensitive to PHC contamination, with toxicity decreasing over time. In contrast, gross mineralization was not sensitive to PHC contamination. Toxic response of gross nitrification was comparable to potential nitrification activity (PNA) with similar EC25 (effective concentration causing a 25% effect in the test population) values determined by both measurement endpoints (400 mg kg(-1) for gross nitrification compared to 200 mg kg(-1) for PNA), indicating that potential microbial activity assays are good surrogates for in situ toxicity of PHC contamination in polar regions. Copyright © 2011 SETAC.

Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system.

PubMed

Balenovic, Dijana; Bencic, Martina Lovric; Udovicic, Mario; Simonji, Karol; Hanzevacki, Jadranka Separovic; Barisic, Ivan; Kranjcevic, Stjepan; Prkacin, Ingrid; Coric, Vedran; Brcic, Luka; Coric, Marijana; Brcic, Iva; Borovic, Suzana; Radic, Bozo; Drmic, Domagoj; Vrcic, Hrvoje; Seiwerth, Sven; Sikiric, Predrag

2009-08-07

Pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) reversed congestive heart failure and various arrhythmias, influenced the NO-system and showed no proarrhythmic effect. In therapy analogy, we challenged rats with digitalis, to show attenuation by BPC 157 and the relation between the NO-system and digitalis toxicity. (i). BPC 157 prophylactic effect. Development of cumulative intravenous digitalis toxicity, BPC 157 (50 microg, 10 microg, 10 ng/kg applied intravenously immediately before a methyldigoxin increment regimen (2.0/1.5/1.5/1.0 mg/kg at 15 min-intervals, total dose 6.0 mg/kg/45 min)) reduced the number of ventricular premature beats, prolonged the time before onset of ventricular tachycardia, reduced ventricular tachycardia and AV-block duration (microg-regimes) or reduced mainly the AV-block duration (ng-regimen). (ii). BPC 157 therapy. Advanced methyldigoxin toxicity (6.0 mg/kg i.v. bolus). BPC 157 applied at the 20th second of the grade 3 AV-block shortened AV-blocks, mitigated a further digitalis toxicity course. Ventricular tachycardias were either avoided (50 microg), or markedly reduced (10 microg, 10 ng). Fatal outcome was either avoided (50 microg), reduced (10 microg), or only delayed (10 ng) (iii) BPC 157, L-NAME, l-arginine, L-NAME+l-arginine application. L-NAME-application (5 mg/kg i.p.) aggravated methyldigoxin-arrhythmias. l-arginine (200 mg/kg i.p.) alone had no effect but blunted L-NAME-exaggeration (L-NAME+l-arginine). In this respect, BPC 157 (50 microg/kg i.p.) was prophylactically and therapeutically more effective: the antagonism of L-NAME with BPC 157 produced an effect similar to BPC 157 alone. In conclusion, digitalis-induced arrhythmias in rats could be prevented and counteracted by pentadecapeptide BPC 157, mainly through an interaction with the NO-system.

PBPK Models, BBDR Models, and Virtual Tissues: How Will They Contribute to the Use of Toxicity Pathways in Risk Assessment?

EPA Science Inventory

Accuracy in risk assessment, which is desirable in order to ensure protection of the public health while avoiding over-regulation of economically-important substances, requires quantitatively accurate, in vivo descriptions of dose-response and time-course behaviors. This level of...

40 CFR 104.7 - Powers of Presiding Officer.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 21 2010-07-01 2010-07-01 false Powers of Presiding Officer. 104.7... HEARINGS ON EFFLUENT STANDARDS FOR TOXIC POLLUTANTS § 104.7 Powers of Presiding Officer. The Presiding...) of the Act. He shall take all necessary action to avoid delay and to maintain order. He shall have...

40 CFR 104.7 - Powers of Presiding Officer.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 22 2011-07-01 2011-07-01 false Powers of Presiding Officer. 104.7... HEARINGS ON EFFLUENT STANDARDS FOR TOXIC POLLUTANTS § 104.7 Powers of Presiding Officer. The Presiding...) of the Act. He shall take all necessary action to avoid delay and to maintain order. He shall have...

Spider mite infestations reduce Bacillus thuringiensis toxin concentration in corn leaves and predators avoid spider mites that have fed on Bacillus thuringiensis corn

USDA-ARS?s Scientific Manuscript database

Transgenic crops containing pyramid-stacked genes for Bacillus thuringiensis derived toxins for controlling coleopteran and lepidopteran pests are increasingly common. As part of environmental risk assessments, these crops are evaluated for toxicity against non-target organisms, and for their poten...

Phenobarbital Treatment at a Neonatal Age Results in Decreased Efficacy of Omeprazole in Adult Mice

PubMed Central

Tien, Yun-Chen; Piekos, Stephanie C.; Pope, Chad

2017-01-01

Drug-drug interactions (DDIs) occur when the action of one drug interferes with or alters the activity of another drug taken concomitantly. This can lead to decreased drug efficacy or increased toxicity. Because of DDIs, physicians in the clinical practice attempt to avoid potential interactions when multiple drugs are coadministrated; however, there is still a large knowledge gap in understanding how drugs taken in the past can contribute to DDIs in the future. The goal of this study was to investigate the consequence of neonatal drug exposure on efficacy of other drugs administered up through adult life. We selected a mouse model to test phenobarbital exposure at a neonatal age and its impact on efficacy of omeprazole in adult life. The results of our experiment show an observed decrease in omeprazole’s ability to raise gastric pH in adult mice that received single or multiple doses of phenobarbital at a neonatal age. This effect may be associated with the permanent induction of cytochrome P450 enzymes in adult liver after neonatal phenobarbital treatment. Our data indicates that DDIs may result from drugs administered in the past in an animal model and should prompt re-evaluation of how DDIs are viewed and how to avoid long-term DDIs in clinical practice. PMID:28062542

Behavioral response and kinetics of terrestrial atrazine exposure in American toads (bufo americanus)

USGS Publications Warehouse

Storrs, Mendez S.I.; Tillitt, D.E.; Rittenhouse, T.A.G.; Semlitsch, R.D.

2009-01-01

Amphibians in terrestrial environments obtain water through a highly vascularized pelvic patch of skin. Chemicals can also be exchanged across this patch. Atrazine (ATZ), a widespread herbicide, continues to be a concern among amphibian ecologists based on potential exposure and toxicity. Few studies have examined its impact on the terrestrial juvenile or adult stages of toads. In the current study, we asked the following questions: (1) Will juvenile American toads (Bufo americanus) avoid soils contaminated with ATZ? (2) Can they absorb ATZ across the pelvic patch? (3) If so, how is it distributed among the organs and eventually eliminated? We conducted a behavioral choice test between control soil and soil dosed with ecologically relevant concentrations of ATZ. In addition, we examined the uptake, distribution, and elimination of water dosed with 14C-labeled ATZ. Our data demonstrate that toads do not avoid ATZ-laden soils. ATZ crossed the pelvic patch rapidly and reached an apparent equilibrium within 5 h. The majority of the radiolabeled ATZ ended up in the intestines, whereas the greatest concentrations were observed in the gall bladder. Thus, exposure of adult life stages of amphibians through direct uptake of ATZ from soils and runoff water should be considered in risk evaluations. ?? 2009 Springer Science+Business Media, LLC.

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

PubMed

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

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

Volatile secondary metabolites as aposematic olfactory signals and defensive weapons in aquatic environments

PubMed Central

Giordano, Giuseppe; Carbone, Marianna; Ciavatta, Maria Letizia; Silvano, Eleonora; Gavagnin, Margherita; Garson, Mary J.; Cheney, Karen L.; Mudianta, I Wayan; Russo, Giovanni Fulvio; Villani, Guido; Magliozzi, Laura; Zidorn, Christian; Cutignano, Adele; Fontana, Angelo; Ghiselin, Michael T.

2017-01-01

Olfaction is considered a distance sense; hence, aquatic olfaction is thought to be mediated only by molecules dissolved in water. Here, we challenge this view by showing that shrimp and fish can recognize the presence of hydrophobic olfactory cues by a “tactile” form of chemoreception. We found that odiferous furanosesquiterpenes protect both the Mediterranean octocoral Maasella edwardsi and its specialist predator, the nudibranch gastropod Tritonia striata, from potential predators. Food treated with the terpenes elicited avoidance responses in the cooccurring shrimp Palaemon elegans. Rejection was also induced in the shrimp by the memory recall of postingestive aversive effects (vomiting), evoked by repeatedly touching the food with chemosensory mouthparts. Consistent with their emetic properties once ingested, the compounds were highly toxic to brine shrimp. Further experiments on the zebrafish showed that this vertebrate aquatic model also avoids food treated with one of the terpenes, after having experienced gastrointestinal malaise. The fish refused the food after repeatedly touching it with their mouths. The compounds studied thus act simultaneously as (i) toxins, (ii) avoidance-learning inducers, and (iii) aposematic odorant cues. Although they produce a characteristic smell when exposed to air, the compounds are detected by direct contact with the emitter in aquatic environments and are perceived at high doses that are not compatible with their transport in water. The mouthparts of both the shrimp and the fish have thus been shown to act as “aquatic noses,” supporting a substantial revision of the current definition of the chemical senses based upon spatial criteria. PMID:28289233

QSAR modeling of acute toxicity on mammals caused by aromatic compounds: the case study using oral LD50 for rats.

PubMed

Rasulev, Bakhtiyor; Kusić, Hrvoje; Leszczynska, Danuta; Leszczynski, Jerzy; Koprivanac, Natalija

2010-05-01

The goal of the study was to predict toxicity in vivo caused by aromatic compounds structured with a single benzene ring and the presence or absence of different substituent groups such as hydroxyl-, nitro-, amino-, methyl-, methoxy-, etc., by using QSAR/QSPR tools. A Genetic Algorithm and multiple regression analysis were applied to select the descriptors and to generate the correlation models. The most predictive model is shown to be the 3-variable model which also has a good ratio of the number of descriptors and their predictive ability to avoid overfitting. The main contributions to the toxicity were shown to be the polarizability weighted MATS2p and the number of certain groups C-026 descriptors. The GA-MLRA approach showed good results in this study, which allows the building of a simple, interpretable and transparent model that can be used for future studies of predicting toxicity of organic compounds to mammals.

Co-release of hexabromocyclododecane (HBCD) and Nano- and microparticles from thermal cutting of polystyrene foams.

PubMed

Zhang, Haijun; Kuo, Yu-Ying; Gerecke, Andreas C; Wang, Jing

2012-10-16

Polystyrene foam is a very important insulation material, and hexabromocyclododecane (HBCD) is frequently used as its flame retardant. HBCD is persistent, bioaccumulative, and toxic, and therefore workplace exposure and environmental emission should be avoided. In this study, we investigated the co-release of HBCD and aerosol particles during the thermal cutting of expanded polystyrene foam (EPS) and extruded polystyrene foam (XPS). The generated particles were simultaneously measured by a fast mobility particle sizer (FMPS) and collected by a cascade impactor (NanoMoudi). In the breathing zone of a cutting worker, the number concentration of aerosol particles was above 1 × 10(12) particles m(-3), and the air concentration of HBCD was more than 50 μg m(-3). Most of the released HBCD was partitioned into particles with an aerodynamic diameter at the nanometer scale. The average concentrations of HBCD in these submicrometer particles generated from the thermal cutting of EPS and XPS were 13 times and 15 times higher than the concentrations in raw foams, respectively. An occupational exposure assessment indicated that more than 60% of HBCD and 70% of particles deposited in the lung of cutting worker would be allocated to the alveolar region. The potential subchronic (or chronic) toxicity jointly caused by the particles and HBCD calls for future studies.

NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood.

PubMed

Kremer, Laura S; Danhauser, Katharina; Herebian, Diran; Petkovic Ramadža, Danijela; Piekutowska-Abramczuk, Dorota; Seibt, Annette; Müller-Felber, Wolfgang; Haack, Tobias B; Płoski, Rafał; Lohmeier, Klaus; Schneider, Dominik; Klee, Dirk; Rokicki, Dariusz; Mayatepek, Ertan; Strom, Tim M; Meitinger, Thomas; Klopstock, Thomas; Pronicka, Ewa; Mayr, Johannes A; Baric, Ivo; Distelmaier, Felix; Prokisch, Holger

2016-10-06

To safeguard the cell from the accumulation of potentially harmful metabolic intermediates, specific repair mechanisms have evolved. APOA1BP, now renamed NAXE, encodes an epimerase essential in the cellular metabolite repair for NADHX and NADPHX. The enzyme catalyzes the epimerization of NAD(P)HX, thereby avoiding the accumulation of toxic metabolites. The clinical importance of the NAD(P)HX repair system has been unknown. Exome sequencing revealed pathogenic biallelic mutations in NAXE in children from four families with (sub-) acute-onset ataxia, cerebellar edema, spinal myelopathy, and skin lesions. Lactate was elevated in cerebrospinal fluid of all affected individuals. Disease onset was during the second year of life and clinical signs as well as episodes of deterioration were triggered by febrile infections. Disease course was rapidly progressive, leading to coma, global brain atrophy, and finally to death in all affected individuals. NAXE levels were undetectable in fibroblasts from affected individuals of two families. In these fibroblasts we measured highly elevated concentrations of the toxic metabolite cyclic-NADHX, confirming a deficiency of the mitochondrial NAD(P)HX repair system. Finally, NAD or nicotinic acid (vitamin B3) supplementation might have therapeutic implications for this fatal disorder. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Hunting with lead ammunition is not sustainable: European perspectives.

PubMed

Kanstrup, Niels; Swift, John; Stroud, David A; Lewis, Melissa

2018-03-12

Much evidence demonstrates the adverse effects of lead ammunition on wildlife, their habitats and human health, and confirms that the use of such ammunition has no place within sustainable hunting. We identify the provisions that define sustainable hunting according to European law and international treaties, together with their guidance documents. We accept the substantial evidence for lead's actual and potential effects on wildlife, habitats and health as persuasive and assess how these effects relate to stated provisions for sustainability and hunting. We evaluate how continued use of lead ammunition negatively affects international efforts to halt loss of biodiversity, sustain wildlife populations and conserve their habitats. We highlight the indiscriminate and avoidable health and welfare impacts for large numbers of exposed wild animals as ethically unsustainable. In societal terms, continued use of lead ammunition undermines public perceptions of hunting. Given the existence of acceptable, non-toxic alternatives for lead ammunition, we conclude that hunting with lead ammunition cannot be justified under established principles of public/international policy and is not sustainable. Changing from lead ammunition to non-toxic alternatives will bring significant nature conservation and human health gains, and from the hunter's perspective will enhance societal acceptance of hunting. Change will create opportunities for improved constructive dialogue between hunting stakeholders and others engaged with enhancing biodiversity and nature conservation objectives.

Combined cyto/genotoxic activity of a selected antineoplastic drug mixture in human circulating blood cells.

PubMed

Gajski, Goran; Gerić, Marko; Domijan, Ana-Marija; Garaj-Vrhovac, Vera

2016-12-01

Antineoplastic drugs are highly cytotoxic chemotherapeutic agents that can often interfere directly or indirectly with the cell's genome. In an environmental or medical setting simultaneous exposure may occur. Such multiple exposures may pose a higher risk than it could be assumed from the studies evaluating the effect of a single substance. Therefore, in the present study we tested the combined cyto/genotoxicity of a mixture of selected antineoplastic drugs with different mechanisms of action (5-fluorouracil, etoposide, and imatinib mesylate) towards human lymphocytes in vitro. The results suggest that the selected antineoplastic drug mixture is potentially cyto/genotoxic and that it can induce cell and genome damage even at low concentrations. Moreover, the changes in the measured oxidative stress parameters suggest the participation of reactive oxygen species in the cyto/genotoxicity of the selected mixture. The obtained results indicate not only that such mixtures may pose a risk to cell and genome integrity, but also that single compound toxicity data are not sufficient for the predicting toxicity in a complex environment. Altogether, the results emphasise the need for further toxicological screening of antineoplastic drug mixtures, especially at low environmentally relevant concentrations, as to avoid any possible adverse effects on the environment and human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Estimating the Potential Toxicity of Chemicals Associated with Hydraulic Fracturing Operations Using Quantitative Structure-Activity Relationship Modeling

EPA Pesticide Factsheets

Researchers facilitated evaluation of chemicals that lack chronic oral toxicity values using a QSAR model to develop estimates of potential toxicity for chemicals used in HF fluids or found in flowback or produced water

Updated indicators of Swedish national human toxicity and ecotoxicity footprints using USEtox 2.01

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

Nordborg, Maria, E-mail: maria.nordborg@chalmers.se; Arvidsson, Rickard; Finnveden, Göran

In a recent paper, Sörme et al. (Environ. Impact Assess. Rev., 56, 2016), took a first step towards an indicator of a national chemical footprint, and applied it to Sweden. Using USEtox 1.01, they calculated national impact potentials for human toxicity and ecotoxicity. The results showed that zinc dominated impacts, both for human toxicity and ecotoxicity. We calculated updated indicators of the Swedish national human toxicity and ecotoxicity footprint using USEtox 2.01. We also compared impact potentials based on USEtox with the mass of chemical emissions. The two model versions produced relatively consistent results. Zinc is still a major contributormore » to the human toxicity and ecotoxicity impact potentials when characterized with USEtox 2.01. The mass-based indicator pinpoints somewhat different substances than the impact-based indicators. - Highlights: • USEtox 1.01 and 2.01 are relatively consistent in identifying the substances with largest impact potentials. • Metals were identified as a priority group of substances for both human toxicity and ecotoxicity. • Zinc is a major contributor to the human toxicity impact potential, in both model versions. • Zinc’s dominance concerning human toxicity sharply contrasts results from other studies: this is somewhat of a paradox. • Using the mass of chemical emissions as a simplified indicator pinpoints somewhat different substances.« less

Safety of methionine, a novel biopesticide, to adult and larval honey bees (Apis mellifera L.).

PubMed

Weeks, Emma N I; Schmehl, Daniel R; Baniszewski, Julie; Tomé, Hudson V V; Cuda, James P; Ellis, James D; Stevens, Bruce R

2018-03-01

Methionine is an essential/indispensible amino acid nutrient required by adult and larval honey bees (Apis mellifera L. [Hymenoptera: Apidae]). Bees are unable to rear broods on pollen deficient in methionine, and reportedly behaviorally avoid collecting pollen or nectar from florets deficient in methioinine. In contrast, it has been demonstrated that methionine is toxic to certain pest insects; thus it has been proposed as an effective biopesticide. As an ecofriendly integrated pest management agent, methionine boasts a novel mode of action differentiating it from conventional pesticides, while providing non-target safety. Pesticides that minimize collateral effects on bees are desirable, given the economic and ecological concerns about honey bee health. The aim of the present study was to assess the potential impact of the biopesticide methionine on non-target adult and larval honey bees. Acute contact adult toxicology bioassays, oral adult assessments and chronic larval toxicity assessments were performed as per U.S. Environmental Protection Agency (EPA) requirements. Our results demonstrated that methionine fits the U.S. EPA category of practically nontoxic (i.e. lethal dose to 50% mortality or LD 50 > 11µg/bee) to adult honey bees. The contact LD 50 was > 25µg/bee and the oral LD 50 was > 100µg/bee. Mortality was observed in larval bees that ingested DL-methionine (effective concentration to 50% mortality or EC 50 560µg/bee). Therefore, we conclude that methionine poses little threat to the health of the honey bee, due to unlikely exposure at concentrations shown to elicit toxic effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Problems analysis and new fabrication strategies of mediated electrochemical biosensors for wastewater toxicity assessment.

PubMed

Yang, Yajie; Fang, Deyu; Liu, Yanran; Liu, Runze; Wang, Xiaoshen; Yu, Yuan; Zhi, Jinfang

2018-06-15

Conventional mediated electrochemical biosensors for toxicity assessment were almost based on 'one-pot' principle, i.e., mediators and the under-test chemicals were mixed together in the same vessel. In this process, the electron mediator is assumed to be merely an electron acceptor and cannot react with under-test toxicants. Actually，some under-test pollutants (such as metal ions) could react with the electron mediators, thus affecting the detection accuracy and sensitivity of the sensors. It was also found that at least two other interference factors have been ignored in present'one-pot' mediated electrochemical biosensor systems, i.e., (1) the electrochemical sensitivity of mediators to pH; and (2) the potential reactions between under-test chemicals and buffers and the consequent pH changes. In this study, the three ignored interference factors have been investigated systematically and demonstrated by significance tests. Moreover, a solving strategy, an isolation method, is proposed for fabrication of novel mediated electrochemical biosensor to avoid the interference factors existing at present mediated electrochemical biosensor. According to the testing results obtained from the isolation method, IC 50 values of Cu 2+ , Cd 2+ , Zn 2+ , Fe 3+ , Ni 2+ and Cr 3+ were 21.3 mg/L, 3.7 mg/L, 26.7 mg/L, 4.4 mg/L and 10.7 mg/L, respectively. The detection results of four real water samples also suggested this method could be applied for the practical and complex samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of a Rapid Ethylene Glycol Assay: a 4-Year Retrospective Study at an Academic Medical Center.

PubMed

Rooney, Sydney L; Ehlers, Alexandra; Morris, Cory; Drees, Denny; Davis, Scott R; Kulhavy, Jeff; Krasowski, Matthew D

2016-06-01

Ethylene glycol (EG) is a common cause of toxic ingestions. Gas chromatography (GC)-based laboratory assays are the gold standard for diagnosing EG intoxication. However, GC requires specialized instrumentation and technical expertise that limits feasibility for many clinical laboratories. The objective of this retrospective study was to determine the utility of incorporating a rapid EG assay for management of cases with suspected EG poisoning. The University of Iowa Hospitals and Clinics core clinical laboratory adapted a veterinary EG assay (Catachem, Inc.) for the Roche Diagnostics cobas 8000 c502 analyzer and incorporated this assay in an osmolal gap-based algorithm for potential toxic alcohol/glycol ingestions. The main limitation is that high concentrations of propylene glycol (PG), while readily identifiable by reaction rate kinetics, can interfere with EG measurement. The clinical laboratory had the ability to perform GC for EG and PG, if needed. A total of 222 rapid EG and 24 EG/PG GC analyses were documented in 106 patient encounters. Of ten confirmed EG ingestions, eight cases were managed entirely with the rapid EG assay. PG interference was evident in 25 samples, leading to 8 GC analyses to rule out the presence of EG. Chart review of cases with negative rapid EG assay results showed no evidence of false negatives. The results of this study highlight the use of incorporating a rapid EG assay for the diagnosis and management of suspected EG toxicity by decreasing the reliance on GC. Future improvements would involve rapid EG assays that completely avoid interference by PG.

Potentiation of the early visual response to learned danger signals in adults and adolescents

PubMed Central

Howsley, Philippa; Jordan, Jeff; Johnston, Pat

2015-01-01

The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents. PMID:24652856

Effects of soot by-product from the synthesis of engineered metallofullerene nanomaterials on terrestrial invertebrates.

PubMed

Johnson, David R; Boyd, Robert E; Bednar, Anthony J; Weiss, Charles A; Hull, Matt S; Coleman, Jessica G; Kennedy, Alan J; Banks, Cynthia J; Steevens, Jeffery A

2018-02-23

The synthesis of carbon-based nanomaterials is often inefficient, generating large amounts of soot with metals as waste by-product. Currently, there are no specific regulations for disposal of engineered nanomaterials or the waste by-products resulting from their synthesis, so it is presumed that by-products are disposed of in the same way as the parent (bulk) materials. We studied the terrestrial toxicity of soot from gadolinium metallofullerene nanomanufacturing on earthworms (Eisenia fetida) and isopods (Porcellio scaber). The metallofullerene soot consisted of carbon particle agglomerates in the nanometer and submicrometer ranges (1-100 and 101-999 nm, respectively), with metals used during nanomanufacturing detectable on the particles. Despite high metal concentrations (>100 000 mg/kg) in the soot, only a relatively small amount of metals leached out of a spiked field soil, suggesting only moderate mobility. Seven- and 14-d exposures in field soil demonstrated that the soot was only toxic to earthworms at high concentrations (>10 000 mg/kg); however, earthworms avoided spiked soils at lower concentrations (as low as 500 mg/kg) and at lower soil pH. The presence of soot in food and soil did not cause isopod avoidance. These data demonstrate that metallofullerene soot from nanomanufacturing may only be toxic to earthworms at high concentrations representative of improper disposal or accidental spills. However, our results indicate that terrestrial invertebrates may avoid soils contaminated with soot at sublethal concentrations. Environ Toxicol Chem 2018;9999:1-12. Published 2018 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work, and as such, is in the public domain in the United States of America. Published 2018 Wiley Periodicals, Inc. on behalf of SETAC. This article is a US government work, and as such, is in the public domain in the United States of America.

Exploiting Nutritional Value of Staple Foods in the World’s Semi-Arid Areas: Risks, Benefits, Challenges and Opportunities of Sorghum

PubMed Central

Proietti, Ilaria; Frazzoli, Chiara; Mantovani, Alberto

2015-01-01

Sorghum (Sorghum bicolor (L.) Moench) is a drought-resistant crop and an important food resource in terms of nutritional as well as social-economic values, especially in semi-arid environments. Cultivar selection and processing methods have been observed to impact on composition and functional and nutritional value of sorghum. Amino acid imbalance, cyanogenic glycosides, endogenous anti-nutrients, mycotoxins and toxic elements are among factors impairing its nutritional value. This paper reviews possible approaches (varieties selection, production practices, cooking processes) to improve the benefits-to-risks balance of sorghum meal, to mitigate the risk of deficiencies and/or imbalances and to improve effects on human nutrition. Opportunity for avoiding dietary diversification in high sorghum consumers is also discussed, e.g., tryptophan and niacin deficits potentially related to pellagra, or unavailability of proteins and divalent cations (e.g., Fe, Zn) due to the antinutrient activity of phytic acid and tannins. As potential candidate for production investments, the role of sorghum in preserving biological diversity is also considered. PMID:27417755

Exploiting Nutritional Value of Staple Foods in the World's Semi-Arid Areas: Risks, Benefits, Challenges and Opportunities of Sorghum.

PubMed

Proietti, Ilaria; Frazzoli, Chiara; Mantovani, Alberto

2015-03-30

Sorghum (Sorghum bicolor (L.) Moench) is a drought-resistant crop and an important food resource in terms of nutritional as well as social-economic values, especially in semi-arid environments. Cultivar selection and processing methods have been observed to impact on composition and functional and nutritional value of sorghum. Amino acid imbalance, cyanogenic glycosides, endogenous anti-nutrients, mycotoxins and toxic elements are among factors impairing its nutritional value. This paper reviews possible approaches (varieties selection, production practices, cooking processes) to improve the benefits-to-risks balance of sorghum meal, to mitigate the risk of deficiencies and/or imbalances and to improve effects on human nutrition. Opportunity for avoiding dietary diversification in high sorghum consumers is also discussed, e.g., tryptophan and niacin deficits potentially related to pellagra, or unavailability of proteins and divalent cations (e.g., Fe, Zn) due to the antinutrient activity of phytic acid and tannins. As potential candidate for production investments, the role of sorghum in preserving biological diversity is also considered.

Reliable identification and quantification of trichothecenes and other mycotoxins by electron impact and chemical ionization-gas chromatography-mass spectrometry, using an ion-trap system in the multiple mass spectrometry mode. Candidate reference method for complex matrices.

PubMed

Melchert, H U; Pabel, E

2004-11-12

Highly toxic mycotoxins like the trichothecenes can be found as contaminants from the metabolism of fungi in food and food preparations. They can be identified and quantified with great accuracy by GC/MS-measurements. Reliable analytical methods are urgently needed because such mycotoxins are not only toxic substances occurring in nature but also are in the list of biological weapons (e.g. T2-toxin, HT-2-toxin) and have some potential for terroristic attacks. By using GC/MS in the EI- and NCI- or PCI-mode and MS(n)-measurements with a 30 m Rtx 5MS fused-silica capillary column it is possible to identify and quantify all relevant mycotoxins either as underivatized substances or as their TMS-derivatives in extracts from food, food preparations or beverages with very complex matrix-derived background. This method can also be used to determine free ricinine as a biological marker for ricine in terroristic attacks. So laborious and time-consuming steps of sample-preparation can often be diminished. The LOD is in the range of 10-50 pg and the LOQ with linear calibration curves is in the range of 50-5000 pg. The high specificity of these methods helps not only to detect the existence of intentional terroristic or natural food contamination but also to avoid faulty alarm with unnecessary panic in the public. Furthermore, these methods have a high potential in ameliorating the safety of basic food and food products.

Can body composition be used to optimize the dose of platinum chemotherapy in lung cancer? A feasibility study.

PubMed

Crosby, Vincent; D'Souza, Catherine; Bristow, Carina; Proffitt, Amy; Hussain, Asmah; Potter, Vanessa; Hennig, Ivo; O'Connor, Richard; Baracos, Vickie; Wilcock, Andrew

2017-04-01

Current methods of dosing platinum-based chemotherapy are suboptimal. Potentially, taking lean body mass into account may help. To inform the design of a future study, we first examined the feasibility and acceptability of such an approach using dual-energy X-ray absorptiometry (DEXA) and explored aspects suggestive of over- and under-dosing. Patients with lung cancer offered platinum-based chemotherapy over 1 year were identified and, if eligible, invited to take part in a prospective feasibility study. Questionnaires examined acceptability of the DEXA scan and of a future study that randomized between traditional dosing and one adjusted according to body composition. Dose-limiting toxicity (DLT) and a lack of neutropenia explored potential over- and under-dosing, respectively. Of the 173 patients offered chemotherapy, 123 (71%) were ineligible, mostly because of failing entry criteria (84, 49%). Of the 50 approached, 18 (36%) participated, most receiving carboplatin, with 17 providing data. All found a DEXA scan acceptable; other assessments were fully completed, except nadir and pre-chemotherapy blood counts. Most (94%) were prepared to take part in a future study, although the additional hospital visits for a nadir blood count were unpopular with some. Five (29%) patients experienced six episodes of DLT which resulted in discontinuation (3), dose reduction (2) or change to a less toxic regimen (1). Nine (60%) patients experienced either no (2) or inconsistent (7) neutropenia. A randomized trial appears acceptable and feasible in patients receiving carboplatin. Adjustment of our entry criteria and avoiding a hospital visit for a nadir blood count should aid recruitment.

[Prevention and multimodal therapy of hyperthyroidism].

PubMed

Palitzsch, K-D

2008-12-01

Subclinical and overt hyperthyroidism have been associated with various negative clinical outcomes as for example an increased risk of atrial fibrillation or increased cardiovascular mortality, especially in old age. In order to avoid hyperthyroidism it is strongly recommended not to start any iodine containing drug therapy or to avoid application of contrast agents unless the patient presents with an unremarkable clinical course. TSH suppressive therapy for the treatment of endemic goiter or differentiated low risk thyroid carcinoma is unnecessary, since it favours the development of subclinical hyperthyroidism. Overt hyperthyroidism is treated with antithyroid drugs and/or radioiodine therapy or surgery according to the underlying disease (toxic nodular goiter, Graves' disease).

A comparative assessment of the acute inhalation toxicity of vanadium compounds.

PubMed

Rajendran, N; Seagrave, J C; Plunkett, L M; MacGregor, J A

2016-11-01

Vanadium compounds have become important in industrial processes, resulting in workplace exposure potential and are present in ambient air as a result of fossil fuel combustion. A series of acute nose-only inhalation toxicity studies was conducted in both rats and mice in order to obtain comparative data on the acute toxicity potential of compounds used commercially. V 2 O 3 , V 2 O 4 , and V 2 O 5 , which have different oxidation states (+3, +4, +5, respectively), were delivered as micronized powders; the highly water-soluble and hygroscopic VOSO 4 (+4) could not be micronized and was instead delivered as a liquid aerosol from an aqueous solution. V 2 O 5 was the most acutely toxic micronized powder in both species. Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO 4 was more toxic than the V 2 O 5 particles in mice, but not in rats. These data suggest that an interaction of characteristics, i.e., bioavailability, solubility and oxidation state, as well as species sensitivity, likely affect the toxicity potential of vanadium compounds. Based on clinical observations and gross necropsy findings, the lung appeared to be the target organ for all compounds. The level of hazard posed will depend on the specific chemical form of the vanadium. Future work to define the inhalation toxicity potential of vanadium compounds of various oxidation states after repeated exposures will be important in understanding how the physico-chemical and biological characteristics of specific vanadium compounds interact to affect toxicity potential and the potential risks posed to human health.

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.

Innovating e-waste management: From macroscopic to microscopic scales.

PubMed

Zeng, Xianlai; Yang, Congren; Chiang, Joseph F; Li, Jinhui

2017-01-01

Waste electrical and electronic equipment (WEEE or e-waste) has become a global problem, due to its potential environmental pollution and human health risk, and its containing valuable resources (e.g., metals, plastics). Recycling for e-waste will be a necessity, not only to address the shortage of mineral resources for electronics industry, but also to decline environmental pollution and human health risk. To systematically solve the e-waste problem, more attention of e-waste management should transfer from macroscopic to microscopic scales. E-waste processing technology should be significantly improved to diminish and even avoid toxic substance entering into downstream of material. The regulation or policy related to new production of hazardous substances in recycled materials should also be carried out on the agenda. All the findings can hopefully improve WEEE legislation for regulated countries and non-regulated countries. Copyright © 2016 Elsevier B.V. All rights reserved.

Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review.

PubMed

García-Castellano, José M; Atallah Yordi, Nagib; Reyes, Carolina; Healey, John H

2012-01-01

Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into "good" and "poor" responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients.

Histopathologic and Radiologic Assessment of Chemotherapeutic Response in Ewing's Sarcoma: A Review

PubMed Central

García-Castellano, José M.; Atallah Yordi, Nagib; Reyes, Carolina; Healey, John H.

2012-01-01

Ewing's sarcoma is a highly malignant tumor that metastasizes rapidly and is thus associated with a low survival rate. The intensification of chemotherapy has been shown to improve the overall survival of patients with Ewing's sarcoma. However, intensified chemotherapy can lead to increased toxicity or even the development of secondary malignancies. The stratification of patients with Ewing's sarcoma into “good” and “poor” responders may help guide the administration of progressively more intensified chemotherapy. Thus, an accurate assessment of the chemotherapeutic response, as well as the extent of chemotherapy-induced tumor necrosis, is critical for avoiding potential treatment-related complications in these patients. This paper reviews the methods currently used to evaluate chemotherapeutic response in Ewing's sarcoma, focusing specifically on histopathologic and imaging analyses, and discusses novel therapies and imaging methods that may help improve the overall survival of these patients. PMID:22550418

Current and New Insights in the Sustainable and Green Recovery of Nutritionally Valuable Compounds from Stevia rebaudiana Bertoni.

PubMed

Koubaa, Mohamed; Roselló-Soto, Elena; Šic Žlabur, Jana; Režek Jambrak, Anet; Brnčić, Mladen; Grimi, Nabil; Boussetta, Nadia; Barba, Francisco J

2015-08-12

The South American plant Stevia rebaudiana Bertoni is a great source of noncaloric sweeteners (steviol glycosides), mainly concentrated in its leaves, but also has important antioxidant compounds (vitamin C, polyphenols, chlorophylls, and carotenoids) and other important macro- and micronutrients such as folic acid and all of the essential amino acids except tryptophan. Traditionally, conventional methods have been used to recover nutritionally valuable compounds from plant food matrices. However, nowadays, the need for obtaining greener, sustainable, and viable processes has led both food industries and food scientists to develop new processes in full correspondence with the green extraction concept. This review focuses on some of the most promising nonconventional and emerging technologies, which may constitute a potential alternative to conventional methods or even could be combined to obtain a synergistic effect, thus reducing extraction time as well as solvent consumption and avoiding the use of toxic solvents.

Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

PubMed

Solomon, Beka

2007-02-01

Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

Sodium hydroxide-mediated hydrogel of citrus pectin for preparation of fluorescent carbon dots for bioimaging.

PubMed

Zhao, Xi Juan; Zhang, Wen Lin; Zhou, Zhi Qin

2014-11-01

The citrus process industry produces annually a huge amount of pomace, which is a rich source of citrus pectin. Here, we report the hydrogel of citrus pectin mediated by sodium hydroxide can be used to prepare fluorescent carbon dots (CDs). The introduction of hydrogel can not only make the temperature of the hydrothermal reaction down to 100 °C, but also avoid visually carbonized precipitates in the synthesis process even up to 180 °C. The as-synthesized CDs are well dispersed in water with an average size of 2.7 nm and show cyan fluorescence with high photostability, good biocompatibility. Furthermore, the CDs can act as a potential fluorescent probe for cell imaging. Citrus pectin as a non-toxic carbonaceous precursor for preparation of fluorescent CDs provides a new approach for the efficient utilization of citrus germplasm in future. Copyright © 2014 Elsevier B.V. All rights reserved.

Naloxone administration for suspected opioid overdose: An expanded scope of practice by a basic life support collegiate-based emergency medical services agency.

PubMed

Jeffery, Ryan M; Dickinson, Laura; Ng, Nicholas D; DeGeorge, Lindsey M; Nable, Jose V

2017-04-01

Opioid abuse is a growing and significant public health concern in the United States. Naloxone is an opioid antagonist that can rapidly reverse the respiratory depression associated with opioid toxicity. Georgetown University's collegiate-based emergency medical services (EMS) agency recently adopted a protocol, allowing providers to administer intranasal naloxone for patients with suspected opioid overdose. While normally not within the scope of practice of basic life support prehospital agencies, the recognition of an increasing epidemic of opioid abuse has led many states, including the District of Columbia, to expand access to naloxone for prehospital providers of all levels of training. In particular, intranasal naloxone is a method of administering this medication that potentially avoids needlestick injuries among EMS providers. Universities with collegiate-based EMS agencies are well positioned to provide life-saving treatments for patients acutely ill from opioid overdose.

Heterotrophic cultivation of microalgae for pigment production: A review.

PubMed

Hu, Jianjun; Nagarajan, Dillirani; Zhang, Quanguo; Chang, Jo-Shu; Lee, Duu-Jong

Pigments (mainly carotenoids) are important nutraceuticals known for their potent anti-oxidant activities and have been used extensively as high end health supplements. Microalgae are the most promising sources of natural carotenoids and are devoid of the toxic effects associated with synthetic derivatives. Compared to photoautotrophic cultivation, heterotrophic cultivation of microalgae in well-controlled bioreactors for pigments production has attracted much attention for commercial applications due to overcoming the difficulties associated with the supply of CO 2 and light, as well as avoiding the contamination problems and land requirements in open autotrophic culture systems. In this review, the heterotrophic metabolic potential of microalgae and their uses in pigment production are comprehensively described. Strategies to enhance pigment production under heterotrophic conditions are critically discussed and the challenges faced in heterotrophic pigment production with possible alternative solutions are presented. Copyright © 2017 Elsevier Inc. All rights reserved.

Mind the Gap! A Journey towards Computational Toxicology.

PubMed

Mangiatordi, Giuseppe Felice; Alberga, Domenico; Altomare, Cosimo Damiano; Carotti, Angelo; Catto, Marco; Cellamare, Saverio; Gadaleta, Domenico; Lattanzi, Gianluca; Leonetti, Francesco; Pisani, Leonardo; Stefanachi, Angela; Trisciuzzi, Daniela; Nicolotti, Orazio

2016-09-01

Computational methods have advanced toxicology towards the development of target-specific models based on a clear cause-effect rationale. However, the predictive potential of these models presents strengths and weaknesses. On the good side, in silico models are valuable cheap alternatives to in vitro and in vivo experiments. On the other, the unconscious use of in silico methods can mislead end-users with elusive results. The focus of this review is on the basic scientific and regulatory recommendations in the derivation and application of computational models. Attention is paid to examine the interplay between computational toxicology and drug discovery and development. Avoiding the easy temptation of an overoptimistic future, we report our view on what can, or cannot, realistically be done. Indeed, studies of safety/toxicity represent a key element of chemical prioritization programs carried out by chemical industries, and primarily by pharmaceutical companies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Tsitomeneas, S. Th., E-mail: stsit@teipir.gr; Vourlias, K., E-mail: kvourlias@yahoo.gr; Geronikolou, St. A., E-mail: sgeronik@bioacademy.gr

The electrical and electronic waste (e-waste) management is a global environmental problem dominated by the precautionary principle application, resulted to preliminary and ambiguous potential adverse effects, of extensive scientific uncertainty. In order to overcome the detected stochastic effects confusions in this field, we propose the inclusion of the principles of justification-optimization-limitation and of prudent avoidance. This model is already, established in radiation protection, so that toxicity as a result of the e-waste management would decrease, whilst the precious metals would be saved. We, further, resolve the classification of rejected items as reusable or as waste, so that the procedure ofmore » dismantling and recycling becomes easier, and the collecting-transporting-placement at an e-waste landfill would be safer. In conclusion, our proposing pattern in the e-waste management enforces the sustainable reducing-reusing-recycling, saves time/money and advances safety by including more sources of e-waste (military, medical etc) that were excluded previously.« less

Elution characteristics of teicoplanin-loaded biodegradable borate glass/chitosan composite.

PubMed

Jia, Wei-Tao; Zhang, Xin; Zhang, Chang-Qing; Liu, Xin; Huang, Wen-Hai; Rahaman, Mohamed N; Day, Delbert E

2010-03-15

Local antibiotic delivery system has an advantage over systemic antibiotic for osteomyelitis treatment due to the delivery of high local antibiotic concentration while avoiding potential systemic toxicity. Composite biomaterials with multifunctional roles, consisting of a controlled antibiotic release, a mechanical (load-bearing) function, and the ability to promote bone regeneration, gradually become the most active area of investigation and development of local antibiotic delivery vehicles. In the present study, a composite of borate glass and chitosan (designated BG/C) was developed as teicoplanin delivery vehicle. The in vitro elution kinetics and antibacterial activity of teicoplanin released from BG/C composite as a function of immersion time were determined. Moreover, the pH changes of eluents and the bioactivity of the composite were characterized using scanning electron microscopy coupled with energy-dispersive spectroscopy and X-ray diffraction analysis. 2009 Elsevier B.V. All rights reserved.

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...

Potential impact of seawater uranium extraction on marine life

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

Park, Jiyeon; Jeters, Robert T.; Kuo, Li-Jung

A variety of adsorbent materials have been developed to extract uranium from seawater as an alternative traditional terrestrial mining. A large-scale deployment of these adsorbents would be necessary to recover useful quantities of uranium and this raises a number of concerns regarding potential impacts on the surrounding marine environment. Two concerns are whether or not the adsorbent materials are toxic and any potentially harmful effects that may result from depleting uranium or vanadium (also highly concentrated by the adsorbents) from the local environment. To test the potential toxicity of the adsorbent with or without bound metals, Microtox assays were usedmore » to test both direct contact toxicity and the toxicity of any leachate in the seawater. The Microtox assay was chosen because it the detection of non-specific mechanisms of toxicity. Toxicity was not observed with leachates from any of 68 adsorbent materials that were tested, but direct contact with some adsorbents at very high adsorbent con-centrations exhibited toxicity. These concentrations are, however, very unlikely to be seen in the actual marine deployment. Adsor-bents that accumulated uranium and trace metals were also tested for toxicity, and no toxic effect was observed. Biofouling on the adsorbents and in columns or flumes containing the adsorbents also indicates that the adsorbents are not toxic and that there may not be an obvious deleterious effect resulting from removing uranium and vanadium from seawater. An extensive literature search was also performed to examine the potential impact of uranium and vanadium extraction from seawater on marine life using the Pacific Northwest National Laboratory’s (PNNL’s) document analysis tool, IN-SPIRE™. Although other potential environmental effects must also be considered, results from both the Microtox assay and the literature search provide preliminary evidence that uranium extraction from seawater could be performed with minimal impact on marine fauna.« less

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

DTIC Science & Technology

2014-10-11

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

Potential resource and toxicity impacts from metals in waste electronic devices.

PubMed

Woo, Seung H; Lee, Dae Sung; Lim, Seong-Rin

2016-04-01

As a result of the continuous release of new electronic devices, existing electronic devices are quickly made obsolete and rapidly become electronic waste (e-waste). Because e-waste contains a variety of metals, information about those metals with the potential for substantial environmental impact should be provided to manufacturers, recyclers, and disposers to proactively reduce this impact. This study assesses the resource and toxicity (i.e., cancer, noncancer, and ecotoxicity) potentials of various heavy metals commonly found in e-waste from laptop computers, liquid-crystal display (LCD) monitors, LCD TVs, plasma TVs, color cathode ray tube (CRT) TVs, and cell phones and then evaluates such potentials using life cycle impact-based methods. Resource potentials derive primarily from Cu, Sb, Ag, and Pb. Toxicity potentials derive primarily from Pb, Ni, and Hg for cancer toxicity; from Pb, Hg, Zn, and As for noncancer toxicity; and from Cu, Pb, Hg, and Zn for ecotoxicity. Therefore, managing these heavy metals should be a high priority in the design, recycling, and disposal stages of electronic devices. © 2015 SETAC.

26 CFR 1.860G-3 - Treatment of foreign persons.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of a residual interest with tax avoidance potential—(1) In general. A transfer of a residual interest that has tax avoidance potential is disregarded for all Federal tax purposes if the transferee is a foreign person. Thus, if a residual interest with tax avoidance potential is transferred to a foreign...

Conditioned food aversion to control outbreaks of intoxication by Ipomoea carnea and Turbina cordata in goats

USDA-ARS?s Scientific Manuscript database

Conditioned food aversion is used to train livestock to avoid the ingestion of toxic plants. This technique was used to control Turbina cordata poisoning in goats in one farm, and to control Ipomoea carnea subsp. istulosa poisoning in another farm. The goats were penned at night and the next mornin...

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

PubMed

Voss, Kenneth; Ryu, Dojin; Jackson, Lauren; Riley, Ronald; Gelineau-van Waes, Janee

2017-08-23

Fumonisins are mycotoxins found in corn. They are toxic to animals and cause cancer in rodents and neural tube defects in LM/Bc mice. Reducing their concentrations in corn-based foods is therefore desirable. Chemical analysis or in vitro bioassays of food extracts might not detect toxic fumonisin reaction products that are unknown or unextractable from food matrices, thus potentially underestimating in vivo toxicity. The effectiveness of two common cooking methods, extrusion and nixtamalization (alkaline cooking), to reduce the toxicity of fumonisin-contaminated corn grits (extrusion) and whole kernel corn (nixtamalization) was shown by means of rat feeding bioassays using fumonisin-specific kidney effects as indicators of potential toxicity. A third bioassay showed that in contrast to fumonisin B 1 (FB 1 ), hydrolyzed fumonisin B 1 (HFB 1 ; formed from FB 1 during nixtamalization) did not cause neural tube defects in LM/Bc mice. The findings indicate that extrusion and nixtamalization reduce the potential toxicity of FB 1 -contaminated corn.

Circuits Regulating Pleasure and Happiness-Mechanisms of Depression.

PubMed

Loonen, Anton J M; Ivanova, Svetlana A

2016-01-01

According to our model of the regulation of appetitive-searching vs. distress-avoiding behaviors, the motivation to display these essential conducts is regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits, including the core and the shell parts of the nucleus accumbens, respectively. An entire series of basal ganglia, running from the caudate nucleus on one side, to the centromedial amygdala on the other side, controls the intensity of these reward-seeking and misery-fleeing behaviors by stimulating the activity of the (pre)frontal and limbic cortices. Hyperactive motivation to display behavior that potentially results in reward induces feelings of hankering (relief leads to pleasure). Hyperactive motivation to exhibit behavior related to avoidance of misery results in dysphoria (relief leads to happiness). These two systems collaborate in a reciprocal fashion. In clinical depression, a mismatch exists between the activities of these two circuits: the balance is shifted to the misery-avoiding side. Five theories have been developed to explain the mechanism of depressive mood disorders, including the monoamine, biorhythm, neuro-endocrine, neuro-immune, and kindling/neuroplasticity theories. This paper describes these theories in relationship to the model (described above) of the regulation of reward-seeking vs. misery-avoiding behaviors. Chronic stress that leads to structural changes may induce the mismatch between the two systems. This mismatch leads to lack of pleasure, low energy, and indecisiveness, on one hand, and dysphoria, continuous worrying, and negative expectations on the other hand. The neuroplastic effects of monoamines, cortisol, and cytokines may mediate the induction of these structural alterations. Long-term exposure to stressful situations (particularly experienced during childhood) may lead to increased susceptibility for developing this condition. This hypothesis opens up the possibility of treating depression with psychotherapy. Genetic and other biological factors (toxic, infectious, or traumatic) may increase sensitivity to the induction of relevant neuroplastic changes. Reversal or compensation of these neuroplastic adjustments may explain the effects of biological therapies in treating depression.

Circuits Regulating Pleasure and Happiness—Mechanisms of Depression

PubMed Central

Loonen, Anton J. M.; Ivanova, Svetlana A.

2016-01-01

According to our model of the regulation of appetitive-searching vs. distress-avoiding behaviors, the motivation to display these essential conducts is regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits, including the core and the shell parts of the nucleus accumbens, respectively. An entire series of basal ganglia, running from the caudate nucleus on one side, to the centromedial amygdala on the other side, controls the intensity of these reward-seeking and misery-fleeing behaviors by stimulating the activity of the (pre)frontal and limbic cortices. Hyperactive motivation to display behavior that potentially results in reward induces feelings of hankering (relief leads to pleasure). Hyperactive motivation to exhibit behavior related to avoidance of misery results in dysphoria (relief leads to happiness). These two systems collaborate in a reciprocal fashion. In clinical depression, a mismatch exists between the activities of these two circuits: the balance is shifted to the misery-avoiding side. Five theories have been developed to explain the mechanism of depressive mood disorders, including the monoamine, biorhythm, neuro-endocrine, neuro-immune, and kindling/neuroplasticity theories. This paper describes these theories in relationship to the model (described above) of the regulation of reward-seeking vs. misery-avoiding behaviors. Chronic stress that leads to structural changes may induce the mismatch between the two systems. This mismatch leads to lack of pleasure, low energy, and indecisiveness, on one hand, and dysphoria, continuous worrying, and negative expectations on the other hand. The neuroplastic effects of monoamines, cortisol, and cytokines may mediate the induction of these structural alterations. Long-term exposure to stressful situations (particularly experienced during childhood) may lead to increased susceptibility for developing this condition. This hypothesis opens up the possibility of treating depression with psychotherapy. Genetic and other biological factors (toxic, infectious, or traumatic) may increase sensitivity to the induction of relevant neuroplastic changes. Reversal or compensation of these neuroplastic adjustments may explain the effects of biological therapies in treating depression. PMID:27891086

Toxicological and chemical screening of Antarctica sediments: Use of whole sediment toxicity tests, microtox, mutatox and semipermeable membrane devices (SPMDs)

USGS Publications Warehouse

Cleveland, Laverne; Little, Edward E.; Petty, Jimmie D.; Johnson, B. Thomas; Lebo, Jon A.; Orazio, Carl E.; Dionne, Jane

1997-01-01

Eight whole sediment samples from Antarctica (four from Winter Quarters Bay and four from McMurdo Sound) were toxicologically and chemically evaluated. Also, the influence of ultraviolet radiation on the toxicity and bioavailability of contaminants associated with the sediment samples was assessed. The evaluations were accomplished by use of a 10-day whole sediment test with Leptocheirus plumulosus, Microtox®, Mutatox® and semipermeable membrane devices (SPMDs). Winter Quarters Bay sediments contained about 250 ng g−1 (dry weight) total PCBs and 20 μg g−1 total PAHs. These sediments elicited toxicity in the Microtox test and avoidance and inhibited burrowing in the L. plumulosus test. The McMurdo Sound sediment samples contained only trace amounts of PCBs and no PAHs, and were less toxic in both the L. plumulosus and Microtox tests compared to the Winter Quarters Bay sediments. The sediments from McMurdo Sound apparently contained some unidentified substance which was photolytically modified to a more toxic form. The photolytic modification of sediment-associated contaminants, coupled with the polar ozone hole and increased incidence of ultraviolet radiation could significantly increase hazards to Antarctic marine life.

Assessment of Crystal Morphology on Uptake, Particle Dissolution, and Toxicity of Nanoscale Titanium Dioxide on Artemia salina

PubMed Central

Johnson, Martha; Ates, Mehmet; Arslan, Zikri; Farah, Ibrahim; Bogatu, Coneliu

2017-01-01

Knowledge of nanomaterial toxicity is critical to avoid adverse effects on human and environment health. In this study, the influences of crystal morphology on physico-chemical and toxic properties of nanoscale TiO2 (n-TiO2) were investigated. Artemia salina were exposed to anatase, rutile and mixture polymorphs of n-TiO2 in seawater. Short-term (24 h) and long-term (96 h) exposures were conducted in 1, 10 and 100 mg/L suspensions of n-TiO2 in the presence and absence of food. Anatase form had highest accumulation followed by mixture and rutile. Presence of food greatly reduced accumulation. n-TiO2 dissolution was not significant in seawater (p<0.05) nor was influenced from crystal structure. Highest toxic effects occurred in 96h exposure in the order of anatase > mixture > rutile. Mortality and oxidative stress levels increased with increasing n-TiO2 concentration and exposure time (p<0.05). Presence of food in the exposure medium alleviated the oxidative stress, indicating that deprivation from food could promote toxic effects of n-TiO2 under long-term exposure. PMID:29333492

Life cycle assessment of construction and demolition waste management.

PubMed

Butera, Stefania; Christensen, Thomas H; Astrup, Thomas F

2015-10-01

Life cycle assessment (LCA) modelling of construction and demolition waste (C&DW) management was carried out. The functional unit was management of 1 Mg mineral, source separated C&DW, which is either utilised in road construction as a substitute for natural aggregates, or landfilled. The assessed environmental impacts included both non-toxic and toxic impact categories. The scenarios comprised all stages of the end-of-life management of C&DW, until final disposal of all residues. Leaching of inorganic contaminants was included, as was the production of natural aggregates, which was avoided because of the use of C&DW. Typical uncertainties related to contaminant leaching were addressed. For most impact categories, utilisation of C&DW in road construction was preferable to landfilling; however, for most categories, utilisation resulted in net environmental burdens. Transportation represented the most important contribution for most nontoxic impacts, accounting for 60-95 per cent of these impacts. Capital goods contributed with negligible impacts. Leaching played a critical role for the toxic categories, where landfilling had lower impacts than utilisation because of the lower levels of leachate per ton of C&DW reaching the groundwater over a 100-year perspective. Leaching of oxyanions (As, V and Sb) was critical with respect to leaching. Typical experimental uncertainties in leaching data did not have a pivotal influence on the results; however, accounting for Cr immobilisation in soils as part of the impact assessment was critical for modelling the leaching impacts. Compared with the overall life cycle of building and construction materials, leaching emissions were shown to be potentially significant for toxicity impacts, compared with contributions from production of the same materials, showing that end-of-life impacts and leaching should not be disregarded when assessing environmental impacts from construction products and materials. CO2 uptake in the C&DW corresponding to 15 per cent carbonation could out-balance global warming impacts from transportation; however, carbonation would also likely result in increased toxicity impacts due to higher leaching of oxyanions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Life cycle assessment and residue leaching: The importance of parameter, scenario and leaching data selection

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

Allegrini, E., E-mail: elia@env.dtu.dk; Butera, S.; Kosson, D.S.

Highlights: • Relevance of metal leaching in waste management system LCAs was assessed. • Toxic impacts from leaching could not be disregarded. • Uncertainty of toxicity, due to background activities, determines LCA outcomes. • Parameters such as pH and L/S affect LCA results. • Data modelling consistency and coverage within an LCA are crucial. - Abstract: Residues from industrial processes and waste management systems (WMSs) have been increasingly reutilised, leading to landfilling rate reductions and the optimisation of mineral resource utilisation in society. Life cycle assessment (LCA) is a holistic methodology allowing for the analysis of systems and products andmore » can be applied to waste management systems to identify environmental benefits and critical aspects thereof. From an LCA perspective, residue utilisation provides benefits such as avoiding the production and depletion of primary materials, but it can lead to environmental burdens, due to the potential leaching of toxic substances. In waste LCA studies where residue utilisation is included, leaching has generally been neglected. In this study, municipal solid waste incineration bottom ash (MSWI BA) was used as a case study into three LCA scenarios having different system boundaries. The importance of data quality and parameter selection in the overall LCA results was evaluated, and an innovative method to assess metal transport into the environment was applied, in order to determine emissions to the soil and water compartments for use in an LCA. It was found that toxic impacts as a result of leaching were dominant in systems including only MSWI BA utilisation, while leaching appeared negligible in larger scenarios including the entire waste system. However, leaching could not be disregarded a priori, due to large uncertainties characterising other activities in the scenario (e.g. electricity production). Based on the analysis of relevant parameters relative to leaching, and on general results of the study, recommendations are provided regarding the use of leaching data in LCA studies.« less

[Research progress on potential liver toxic components in traditional Chinese medicine].

PubMed

Wu, Hao; Zhong, Rong-Ling; Xia, Zhi; Huang, Hou-Cai; Zhong, Qing-Xiang; Feng, Liang; Song, Jie; Jia, Xiao-Bin

2016-09-01

In recent years, the proportion of traditional Chinese medicine in scientific research and its clinical use increased gradually. The research result also becomes more and more valuable, but in the process of using traditional Chinese medicine, it also needs to pay more attention. With the gradual deepening of the toxicity of traditional Chinese medicine, some traditional Chinese medicines have also been found to have the potential toxicity, with the exception of some traditional toxicity Chinese medicine. Traditional Chinese medicine in the growth, processing, processing, transportation and other aspects of pollution or deterioration will also cause the side effects to the body. Clinical practice should be based on the theory of traditional Chinese medicine to guide rational drug use and follow the symptomatic medication, the principle of proper compatibility. The constitution of the patients are different, except for a few varieties of traditional Chinese medicines are natural herbs with hepatotoxicity, liver toxicity of most of the traditional Chinese medicine has idiosyncratic features. The liver plays an important role in drug metabolism. It is easy to be damaged by drugs. Therefore, the study of traditional Chinese medicine potential liver toxicity and its toxic components has become one of the basic areas of traditional Chinese medicine research. Based on the review of the literatures, this paper summarizes the clinical classification of liver toxicity, the pathogenesis of target cell injury, and systematically summarizes the mechanism of liver toxicity and toxic mechanism of traditional Chinese medicine. This paper provided ideas for the study of potential liver toxicity of traditional Chinese medicine and protection for clinical safety of traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

Environmental Risk Evaluation System – An Approach to Ranking Risk of Ocean Energy Development on Coastal and Estuarine Environments

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

Copping, Andrea E.; Hanna, Luke A.; Van Cleve, Frances B.

Deployment and operation of ocean energy devices does not represent the first foray into industrialization of the oceans; shipping, nearshore development, waste disposal, subsea mining, oil and gas extraction, and large-scale commercial fishing all coexist in various states of equilibrium with the marine environment. In most cases these industries were developed without a clear understanding of the likely outcomes of large-scale development. In virtually every country where the harvest of ocean energy is emerging, regulators and stakeholders require that the industry examine potential effects of devices, minimize the footprint of effects, and provide management measures that either avoid the impactsmore » or mitigate to further reduce the residual impacts. The ERES analysis is based on scenarios that are consistent with sequences of events that lead to adverse impacts, distinguishing between episodic, intermittent, and chronic risks. In the context of ocean energy development, an episodic scenario might involve the exceedingly rare but potentially devastating event of an oil spill from vessels caused by the presence of the device, while vulnerable receptors are present; understanding the risk of such a scenario involves determining the probability of the occurrence by examining factors such as the petroleum content of ocean energy devices, the vessel traffic volume and the proximity of shipping lanes to the ocean energy devices, the reliability of the control measures to avoid an episodic event, and the likely presence of seabirds, marine mammals, or fish that may be affected by oil. In contrast, chronic risk scenarios involve events or circumstances that are continuous, so that risk characterization involves assessing only the severity of the consequences. An example of a chronic risk scenario might be the toxicity to marine organisms due to low-level chemical releases from anti-biofouling paints and coatings that may be used on devices, and the effect that the level of toxicity may have on marine flora and fauna. Between these two extremes are intermittent events, such as encounters between fish and rotating tidal turbine blades that will occur only when fish are present and the tidal device is turning. A key feature of understanding risk is describing the uncertainty associated with the occurrence of an episodic, intermittent, or chronic event, as well as the uncertainty of the resulting consequences.« less

Daily chlorhexidine bathing does not increase skin toxicity after remission induction or stem cell transplantation.

PubMed

Deeren, Dries; Dewulf, Evelyne; Verfaillie, Lydie

2016-12-01

A recent multicenter study demonstrated that bathing with chlorhexidine reduces the transmission of resistant organisms and the risk of hospital-acquired bloodstream infections in ICUs. We wanted to confirm the feasibility of this strategy in a cohort of patients in a typical intensive haematology unit. Patients treated with remission induction chemotherapy, autologous or allogeneic stem cell transplantation received daily chlorhexidine bathing. To avoid deshydratation of skin, we used prophylactic application of hydrating lotion, replaced by corticosteroid cream in case of skin toxicity of chemotherapy or conditioning. We studied 15 consecutive admissions of 12 patients. Daily chlorhexidine bathing never needed to be interrupted, even though 53% of patients were treated with intravenous cytarabine. Patients were satisfied with the skin treatment and reported few unwanted effects. Daily chlorhexidine bathing was feasible in our intensive haematology unit in all patients and did not increase skin toxicity, even when treated with IV cytarabine.

Distribution and transfer of potentially toxic metal(loid)s in Juncus effusus from the indigenous zinc smelting area, northwest region of Guizhou Province, China.

PubMed

Peng, Yishu; Chen, Jun; Wei, Huairui; Li, Shibin; Jin, Tao; Yang, Ruidong

2018-05-15

We collected samples (i.e., the aerial parts and roots of Juncus effusus and their growth media) in the indigenous zinc smelting area in the northwest region of Guizhou Province, China, and we measured and analyzed potentially toxic metal(loid)s (arsenic, As; cadmium, Cd; chromium, Cr; copper, Cu; mercury, Hg; lead, Pb and zinc, Zn) in these samples. The results include the following: First, there is a high concentration of one or more potentially toxic metal(loid)s in the slag and surrounding soil in the research area. This situation might be caused by metal(loid) damage or contamination due to the circumstances. Additionally, Juncus effusus in the indigenous zinc smelting area are contaminated by some potentially toxic metal(loid)s; since they are used for Chinese medical materials, it is especially significant that their As, Cd and Pb concentrations are greater than their limited standard values. Finally, both the bioconcentration factors and transfer factors for most potentially toxic metal(loid)s in Juncus effusus are less than 1 in the study area. Therefore, we suggest that Juncus effusus could be used for phytostabilization or as a pioneer plant for phytoremediation of potentially toxic metal(loid)s because it has a tolerance and exclusion mechanism for these metal(loid)s in the research district. Copyright © 2018 Elsevier Inc. All rights reserved.

Incidence of potentially avoidable urgent readmissions and their relation to all-cause urgent readmissions

PubMed Central

van Walraven, Carl; Jennings, Alison; Taljaard, Monica; Dhalla, Irfan; English, Shane; Mulpuru, Sunita; Blecker, Saul; Forster, Alan J.

2011-01-01

Background: Urgent, unplanned hospital readmissions are increasingly being used to gauge the quality of care. We reviewed urgent readmissions to determine which were potentially avoidable and compared rates of all-cause and avoidable readmissions. Methods: In a multicentre, prospective cohort study, we reviewed all urgent readmissions that occurred within six months among patients discharged to the community from 11 teaching and community hospitals between October 2002 and July 2006. Summaries of the readmissions were reviewed by at least four practising physicians using standardized methods to judge whether the readmission was an adverse event (poor clinical outcome due to medical care) and whether the adverse event could have been avoided. We used a latent class model to determine whether the probability that each readmission was truly avoidable exceeded 50%. Results: Of the 4812 patients included in the study, 649 (13.5%, 95% confidence interval [CI] 12.5%–14.5%) had an urgent readmission within six months after discharge. We considered 104 of them (16.0% of those readmitted, 95% CI 13.3%–19.1%; 2.2% of those discharged, 95% CI 1.8%–2.6%) to have had a potentially avoidable readmission. The proportion of patients who had an urgent readmission varied significantly by hospital (range 7.5%–22.5%; χ2 = 92.9, p < 0.001); the proportion of readmissions deemed avoidable did not show significant variation by hospital (range 1.2%–3.7%; χ2 = 12.5, p < 0.25). We found no association between the proportion of patients who had an urgent readmission and the proportion of patients who had an avoidable readmission (Pearson correlation 0.294; p = 0.38). In addition, we found no association between hospital rankings by proportion of patients readmitted and rankings by proportion of patients with an avoidable readmission (Spearman correlation coefficient 0.28, p = 0.41). Interpretation: Urgent readmissions deemed potentially avoidable were relatively uncommon, comprising less than 20% of all urgent readmissions following hospital discharge. Hospital-specific proportions of patients who were readmitted were not related to proportions with a potentially avoidable readmission. PMID:21859870

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.

Assessing changes in the toxicity of effluents from intensive marine fish farms over time by using a battery of bioassays.

PubMed

Carballeira, Carlos; Cebro, Alesandra; Villares, Rubén; Carballeira, Alejo

2018-05-01

Although intensive marine fish farming is often assumed to be eco-friendly, the associated activity can lead to chronic exposure of marine organisms to potentially toxic discharges. Moreover, despite the increasing popularity of integrated multi-trophic aquaculture (IMTA), studies of the effects of fish farm effluents are almost non-existent. In the present study, the changes in the toxic potential of effluents from five land-based marine fish farms in NW Spain subjected for different lengths of time to a biodegradation procedure (for 0, 48, 120, and 240 h) were assessed in a battery of bioassays including organisms from different trophic levels (Vibrio fischeri, Isochrysis galbana, and Paracentrotus lividus). The results of the bioassays at the different times were then considered together with farm water flow in the Potential Ecotoxic Effects Probe (PEEP) index. Despite the high volumes of effluents discharged, the generally low toxicity of the effluents hinders assessment of potentially toxic effects. However, dose-response curves and statistical analysis demonstrated the existence of toxic effects during the first five days of the biodegradation procedure, especially immediately after sampling. The proposed modification of the PEEP index better reflects the changes in toxicity over time. Graphical abstract ᅟ.

Changes of toxic metals during biological stabilization and their potential ecological risk assessment.

PubMed

Wang, Hou-cheng; Zeng, Zheng-zhong; Zhang, He-fei; Nan, Zhong-ren

2015-01-01

With various disadvantages of pollution control technologies for toxic metal-contaminated soil, we mixed contaminated soil with sludge for in situ composting to stabilize toxic metals, so plants are enriched to take up the toxic metals. When simulating the above, we added toxic metal solution into sewage sludge, and then composed it with steel slag to determine inhibition of the availability of toxic metals. When toxic metals were added into sludge, the potential ecological index and geoaccumulation index of Cd became high while Zn was low. Steel slag had an inhibited availability of Cd, and when the adjunction of steel slag was 7%, the availability of Cd was lowest. Steel slag promoted the availability of Zn, and when the adjunction of steel slag was 27%, the availability of Zn was highest. Results showed that during composting, with increasing steel slag, Cd stabilizing time was reached sooner but Zn stabilizing time was slower, and the availability of all metals became lower. In the end, composting inhibited the potential ecological index of Cd, but it promoted the potential ecological index of Zn. Steel slag promoted the stability of Cd and Zn as Fe/Mn oxide-bound and residual species. Therefore, composting sludge and steel slag could be used as an effective inhibitor of Zn and Cd pollution.

Analysis of algal chlorophylls and carotenoids

NASA Astrophysics Data System (ADS)

Bidigare, Robert R.

Water samples should be collected with Go-Flo bottles to avoid the contamination problems associated with the latex rubber closure mechanism of Niskin bottles [Williams and Robertson, 1989]. Price et al. [1986] have documented that latex rubber is extremely toxic to marine phytoplankton. It is recommended that only silicone tubing be used to dispense seawater into sample bottles. Seawater is dispensed into opaque Nalgene sample bottles to avoid light shock to deep-living phytoplankton assemblages. If pigment samples are collected to examine the dynamics of the diatoxanthin-diadinoxanthin (DT-DN) xanthophyll cycle, then casts should be performed quickly, i.e. less than 6 minutes, to minimize DT-DN interconversion prior to filtration [Welschmeyer and Hoepffner, in press; Welschmeyer, personal communication, 1990].

Early pregnancy exposure to feto-toxic medications among out-patients in Malawi.

PubMed

Kabuluzi, Ezereth; Campbell, Malcolm; McGowan, Linda; Chirwa, Ellen; Brabin, Loretta

2014-08-01

To estimate the proportion of women in early pregnancy prescribed potentially feto-toxic medications at an out-patient clinic in Malawi. Over six-months the number of women of child-bearing age attending out-patient clinics and prescribed medicines at Mitundu Community Hospital was derived from the hospital's registry and pharmacy records. Women prescribed potentially feto-toxic medicines (using Food and Drug Administration classifications) by medical assessments were subsequently interviewed and pregnancy tested. Exposure to potentially feto-toxic medications was estimated and differences between pregnant and non-pregnant women were described. Of 8970 female outpatients, 1012 (11.3%; 95% CI: 10.6% to 12%) were prescribed potentially feto-toxic medicines. After excluding 740 as unlikely to be pregnant, 209 women had negative pregnancy tests and 63 were confirmed as pregnant, representing one in 16 of women prescribed contraindicated medicines or between 2.8% and 3.5% of all women attending in early pregnancy. Most medicines were FDA rated C or D. Only 152 (55.9%) of these women had been asked about pregnancy and prescribing practices did not discriminate between pregnant and non-pregnant patients. Assessment and prescribing practices for women attending out-patient clinics who might be in early pregnancy were inadequate, increasing the risk of exposure to potentially feto-toxic medicines.

Advanced analysis tools and programs to accelerate the adoption of more natural structures

Treesearch

Christopher G. Hunt; Joseph Jakes; Charles Frihart

2017-01-01

While wood is a highly desirable building material from an ecological and sustainability perspective, we do not understand its fundamental properties nearly as well as we understand competing materials such as steel and concrete. We can avoid toxic preservatives by acetylating wood, but we don’t fundamentally understand why acetylation works. Hydroxymethylated...

On the run: free-living mushroom corals avoiding interaction with sponges

NASA Astrophysics Data System (ADS)

Hoeksema, B. W.; de Voogd, N. J.

2012-06-01

Individuals of the free-living mushroom coral Heliofungia fralinae moved away when placed in contact with fragments of the toxic haplosclerid sponge Callyspongia (Euplacella) biru. This reaction was not evoked by three other sponge species. The experiment demonstrated that mobility of mushroom corals helps them to flee from organisms that secrete secondary metabolites in competition for space.

Biodegradation of Ochratoxin A for Food and Feed Decontamination

PubMed Central

Abrunhosa, Luís; Paterson, Robert R. M.; Venâncio, Armando

2010-01-01

Ochratoxin A (OTA) is one of the most important mycotoxins that is found in food and feed products. It has proven toxic properties, being primarily known for its nephrotoxicity and carcinogenicity to certain animal species. OTA is produced by several species of Aspergillus and Penicillium that can be found in a wide variety of agricultural products, which makes the presence of OTA in these products common. Many countries have statutory limits for OTA, and concentrations need to be reduced to as low as technologically possible in food and feed. The most important measures to be taken to control OTA are preventive in order to avoid fungal growth and OTA production. However, these measures are difficult to implement in all cases with the consequence of OTA remaining in agricultural commodities. Remediation processes are often used to eliminate, reduce or avoid the toxic effects of OTA. Biological methods have been considered increasingly as an alternative to physical and chemical treatments. However, examples of practical applications are infrequent. This review will focus on the (i) known microorganisms and enzymes that are able to biodegrade OTA; (ii) mode of action of biodegradation and (iii) current applications. A critical discussion about the technical applicability of these strategies is presented. PMID:22069627

Recycling Perovskite Solar Cells To Avoid Lead Waste.

PubMed

Binek, Andreas; Petrus, Michiel L; Huber, Niklas; Bristow, Helen; Hu, Yinghong; Bein, Thomas; Docampo, Pablo

2016-05-25

Methylammonium lead iodide (MAPbI3) perovskite based solar cells have recently emerged as a serious competitor for large scale and low-cost photovoltaic technologies. However, since these solar cells contain toxic lead, a sustainable procedure for handling the cells after their operational lifetime is required to prevent exposure of the environment to lead and to comply with international electronic waste disposal regulations. Herein, we report a procedure to remove every layer of the solar cells separately, which gives the possibility to selectively isolate the different materials. Besides isolating the toxic lead iodide in high yield, we show that the PbI2 can be reused for the preparation of new solar cells with comparable performance and in this way avoid lead waste. Furthermore, we show that the most expensive part of the solar cell, the conductive glass (FTO), can be reused several times without any reduction in the performance of the devices. With our simple recycling procedure, we address both the risk of contamination and the waste disposal of perovskite based solar cells while further reducing the cost of the system. This brings perovskite solar cells one step closer to their introduction into commercial systems.

Taste and pheromone perception in the fruit fly Drosophila melanogaster.

PubMed

Ebbs, Michelle L; Amrein, Hubert

2007-08-01

Taste is an essential sense for detection of nutrient-rich food and avoidance of toxic substances. The Drosophila melanogaster gustatory system provides an excellent model to study taste perception and taste-elicited behaviors. "The fly" is unique in the animal kingdom with regard to available experimental tools, which include a wide repertoire of molecular-genetic analyses (i.e., efficient production of transgenics and gene knockouts), elegant behavioral assays, and the possibility to conduct electrophysiological investigations. In addition, fruit flies, like humans, recognize sugars as a food source, but avoid bitter tasting substances that are often toxic to insects and mammals alike. This paper will present recent research progress in the field of taste and contact pheromone perception in the fruit fly. First, we shall describe the anatomical properties of the Drosophila gustatory system and survey the family of taste receptors to provide an appropriate background. We shall then review taste and pheromone perception mainly from a molecular genetic perspective that includes behavioral, electrophysiological and imaging analyses of wild type flies and flies with genetically manipulated taste cells. Finally, we shall provide an outlook of taste research in this elegant model system for the next few years.

Plasma metabolic profiling analysis of toxicity induced by brodifacoum using metabonomics coupled with multivariate data analysis.

PubMed

Yan, Hui; Qiao, Zheng; Shen, Baohua; Xiang, Ping; Shen, Min

2016-10-01

Brodifacoum is one of the most widely used rodenticides for rodent control and eradication; however, human and animal poisoning due to primary and secondary exposure has been reported since its development. Although numerous studies have described brodifacoum induced toxicity, the precise mechanism still needs to be explored. Gas chromatography mass spectrometry (GC-MS) coupled with an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to characterize the metabolic profile of brodifacoum induced toxicity and discover potential biomarkers in rat plasma. The toxicity of brodifacoum was dose-dependent, and the high-dose group obviously manifested toxicity with subcutaneous hemorrhage. The blood brodifacoum concentration showed a positive relation to the ingestion dose in toxicological analysis. Significant changes of twenty-four metabolites were identified and considered as potential toxicity biomarkers, primarily involving glucose metabolism, lipid metabolism and amino acid metabolism associated with anticoagulant activity, nephrotoxicity and hepatic damage. MS-based metabonomics analysis in plasma samples is helpful to search for potential poisoning biomarkers and to understand the underlying mechanisms of brodifacoum induced toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nitrates and herbicides cause higher mortality than the traditional organic fertilizers on the grain beetle, Tenebrio molitor.

PubMed

Castilla, Aurora M; Dauwe, Tom; Mora, Isabel; Malone, Jim; Guitart, Raimon

2010-01-01

We examined experimentally whether fertilizers or herbicides commonly used by farmers affect mortality of the adult grain beetle Tenebrio molitor. After a period of 4 weeks in direct contact with all treatments, a higher percentage of mortality occurred in contact with nitrates than with pig manure or turkey litter. Herbicides (a mixture of glyphosate and 2,4-D: ) caused 100% mortality. Our results also indicate that more beetles escaped from the herbicides and nitrate treatments than from the others, suggesting some kind of behavioural avoidance of toxic environments. The traditional organic fertilizers appear to be less toxic than inorganic fertilizers for Tenebrio molitor.

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.

Health hazards of ceramic artists.

PubMed

Dorevitch, S; Babin, A

2001-01-01

Ceramic artists can be exposed to many hazards including metals (such as lead), fibrogenic dusts (such as silica), heat, repetitive motion, radiation, and toxic emissions from kilns. The health risks of these exposures have not been well characterized among artists, although limited information is available from commercial potteries. Adverse health effects may be prevented by using less hazardous materials (such as lead-free glazes), improved ventilation, and proper work practices. Special precautions must be in place if children have access to the ceramics studio. The use of glazed ceramic dishes can be a risk for lead toxicity. Food should not be stored in glazed ceramics, and pregnant women should avoid daily use of ceramic mugs for drinking hot beverages.

Integrating chemical, toxicological and clinical research to assess the potential of reducing health risks associated with cigarette smoking through reducing toxicant emissions.

PubMed

McAdam, Kevin; Murphy, James; Eldridge, Alison; Meredith, Clive; Proctor, Christopher

2018-06-01

The concept of a risk continuum for tobacco and nicotine products has been proposed, which differentiates products according to their propensity to reduce toxicant exposure and risk. Cigarettes are deemed the most risky and medicinal nicotine the least. We assessed whether a Reduced-Toxicant Prototype (RTP) cigarette could sufficiently reduce exposure to toxicants versus conventional cigarettes to be considered a distinct category in the risk continuum. We present findings from both pre-clinical and clinical studies in order to examine the potential for reduced smoke toxicant emissions to lower health risks associated with cigarette smoking. We conclude that current toxicant reducing technologies are unable to reduce toxicant emissions sufficiently to manifest beneficial disease-relevant changes in smokers. These findings point to a minimum toxicant exposure standard that future potentially reduced risk products would need to meet to be considered for full biological assessment. The RTP met WHO TobReg proposed limits on cigarette toxicant emissions, however the absence of beneficial disease relevant changes in smokers after six months reduced toxicant cigarette use, does not provide evidence that these regulatory proposals will positively impact risks of smoking related diseases. Greater toxicant reductions, such as those that can be achieved in next generation products e.g. tobacco heating products and electronic cigarettes are likely to be necessary to clearly reduce risks compared with conventional cigarettes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

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

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com; Weng, Zuquan; Sun, Liya

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. Inmore » the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.« less

Distribution and Biological Effects of Nanoparticles in the Reproductive System.

PubMed

Liu, Ying; Li, Hongxia; Xiao, Kai

2016-01-01

Nanoparticles have shown great potential in biomedical applications such as imaging probes and drug delivery. However, the increasing use of nanoparticles has raised concerns about their adverse effects on human health and environment. Reproductive tissues and gametes represent highly delicate biological systems with the essential function of transmitting genetic information to the offspring, which is highly sensitive to environmental toxicants. This review aims to summarzie the penetration of physiological barriers (blood-testis barrier and placental barrier), distribution and biological effects of nanoparticles in the reproductive system, which is essential to control the beneficial effects of nanoparticles applications and to avoid their adverse effects on the reproductive system. We referred to a large number of relevant peer-reviewed research articles about the reproductive toxicity of nanoparticles. The comprehensive information was summarized into two parts: physiological barrier penetration and biological effects of nanoparticles in male or female reproductive system; distribution and metabolism of nanoparticles in the reproductive system. The representative examples were also presented in four tables. The in vitro and in vivo studies imply that some nanoparticles are able to cross the blood-testis barrier or placental barrier, and their penetration depends on the physicochemical characteristics of nanoparticles (e.g., composition, shape, particle size and surface coating). The toxicity assays indicate that nanoparticles might induce adverse physiological effects and impede fertility or embryogenesis. The barrier penetration, adverse physiological effects, distribution and metabolism are closely related to physicochemical characteristics of nanoparticles. Further systematic and mechanistic studies using well-characterized nanoparticles, relevant administration routes, and doses relevant to the expected exposure level are required to improve our understanding of biological effects of nanoparticles on the reproductive system.

Effects of optimism on creativity under approach and avoidance motivation

PubMed Central

Icekson, Tamar; Roskes, Marieke; Moran, Simone

2014-01-01

Focusing on avoiding failure or negative outcomes (avoidance motivation) can undermine creativity, due to cognitive (e.g., threat appraisals), affective (e.g., anxiety), and volitional processes (e.g., low intrinsic motivation). This can be problematic for people who are avoidance motivated by nature and in situations in which threats or potential losses are salient. Here, we review the relation between avoidance motivation and creativity, and the processes underlying this relation. We highlight the role of optimism as a potential remedy for the creativity undermining effects of avoidance motivation, due to its impact on the underlying processes. Optimism, expecting to succeed in achieving success or avoiding failure, may reduce negative effects of avoidance motivation, as it eases threat appraisals, anxiety, and disengagement—barriers playing a key role in undermining creativity. People experience these barriers more under avoidance than under approach motivation, and beneficial effects of optimism should therefore be more pronounced under avoidance than approach motivation. Moreover, due to their eagerness, approach motivated people may even be more prone to unrealistic over-optimism and its negative consequences. PMID:24616690

Life cycle assessment of construction and demolition waste management

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

Butera, Stefania, E-mail: stbu@teknologisk.dk; Christensen, Thomas H.; Astrup, Thomas F.

Highlights: • LCA of C&DW utilisation in road vs. C&DW landfilling. • C&DW utilisation in road better than landfilling for most categories. • Transportation is the most important process in non-toxic impact categories. • Leaching of oxyanions is the critical process in toxic impact categories. • Modelling of Cr fate in the subsoil is highly influential to the results. - Abstract: Life cycle assessment (LCA) modelling of construction and demolition waste (C&DW) management was carried out. The functional unit was management of 1 Mg mineral, source separated C&DW, which is either utilised in road construction as a substitute for naturalmore » aggregates, or landfilled. The assessed environmental impacts included both non-toxic and toxic impact categories. The scenarios comprised all stages of the end-of-life management of C&DW, until final disposal of all residues. Leaching of inorganic contaminants was included, as was the production of natural aggregates, which was avoided because of the use of C&DW. Typical uncertainties related to contaminant leaching were addressed. For most impact categories, utilisation of C&DW in road construction was preferable to landfilling; however, for most categories, utilisation resulted in net environmental burdens. Transportation represented the most important contribution for most nontoxic impacts, accounting for 60–95 per cent of these impacts. Capital goods contributed with negligible impacts. Leaching played a critical role for the toxic categories, where landfilling had lower impacts than utilisation because of the lower levels of leachate per ton of C&DW reaching the groundwater over a 100-year perspective. Leaching of oxyanions (As, V and Sb) was critical with respect to leaching. Typical experimental uncertainties in leaching data did not have a pivotal influence on the results; however, accounting for Cr immobilisation in soils as part of the impact assessment was critical for modelling the leaching impacts. Compared with the overall life cycle of building and construction materials, leaching emissions were shown to be potentially significant for toxicity impacts, compared with contributions from production of the same materials, showing that end-of-life impacts and leaching should not be disregarded when assessing environmental impacts from construction products and materials. CO{sub 2} uptake in the C&DW corresponding to 15 per cent carbonation could out-balance global warming impacts from transportation; however, carbonation would also likely result in increased toxicity impacts due to higher leaching of oxyanions.« less

Laboratory toxicity and benthic invertebrate field colonization of Upper Columbia River sediments: finding adverse effects using multiple lines of evidence.

PubMed

Fairchild, J F; Kemble, N E; Allert, A L; Brumbaugh, W G; Ingersoll, C G; Dowling, B; Gruenenfelder, C; Roland, J L

2012-07-01

From 1930 to 1995, the Upper Columbia River (UCR) of northeast Washington State received approximately 12 million metric tons of smelter slag and associated effluents from a large smelter facility located in Trail, British Columbia, approximately 10 km north of the United States-Canadian border. Studies conducted during the past two decades have demonstrated the presence of toxic concentrations of heavy metals in slag-based sandy sediments, including cadmium, copper, zinc, and lead in the UCR area as well as the downstream reservoir portion of Lake Roosevelt. We conducted standardized whole-sediment toxicity tests with the amphipod Hyalella azteca (28-day) and the midge Chironomus dilutus (10-day) on 11 samples, including both UCR and study-specific reference sediments. Metal concentrations in sediments were modeled for potential toxicity using three approaches: (1) probable effects quotients (PEQs) based on total recoverable metals (TRMs) and simultaneously extracted metals (SEMs); (2) SEMs corrected for acid-volatile sulfides (AVS; i.e., ∑SEM - AVS); and (3) ∑SEM - AVS normalized to the fractional organic carbon (f(oc)) (i.e., ∑SEM - AVS/f(oc)). The most highly metal-contaminated sample (∑PEQ(TRM) = 132; ∑PEQ(SEM) = 54; ∑SEM - AVS = 323; and ∑SEM - AVS/(foc) = 64,600 umol/g) from the UCR was dominated by weathered slag sediment particles and resulted in 80% mortality and 94% decrease in biomass of amphipods; in addition, this sample significantly decreased growth of midge by 10%. The traditional ∑AVS - SEM, uncorrected for organic carbon, was the most accurate approach for estimating the effects of metals in the UCR. Treatment of the toxic slag sediment with 20% Resinex SIR-300 metal-chelating resin significantly decreased the toxicity of the sample. Samples ∑SEM - AVS > 244 was not toxic to amphipods or midge in laboratory testing, indicating that this value may be an approximate threshold for effects in the UCR. In situ benthic invertebrate colonization studies in an experimental pond (8-week duration) indicated that two of the most metal-contaminated UCR sediments (dominated by high levels of sand-sized slag particles) exhibited decreased invertebrate colonization compared with sand-based reference sediments. Field-exposed SIR-300 resin samples also exhibited decreased invertebrate colonization numbers compared with reference materials, which may indicate behavioral avoidance of this material under field conditions. Multiple lines of evidence (analytical chemistry, laboratory toxicity, and field colonization results), along with findings from previous studies, indicate that high metal concentrations associated with slag-enriched sediments in the UCR are likely to adversely impact the growth and survival of native benthic invertebrate communities. Additional laboratory toxicity testing, refinement of the applications of sediment benchmarks for metal toxicity, and in situ benthic invertebrate studies will assist in better defining the spatial extent, temporal variations, and ecological impacts of metal-contaminated sediments in the UCR system.

A gallium complex with a new tripodal tris-hydroxypyridinone for potential nuclear diagnostic imaging: solution and in vivo studies of 67Ga-labeled species.

PubMed

Chaves, Sílvia; Mendonça, Ana C; Marques, Sérgio M; Prata, M Isabel; Santos, Ana C; Martins, André F; Geraldes, Carlos F G C; Santos, M Amélia

2011-01-01

The gallium(III) complex of a new tripodal 3-hydroxy-4-pyridinone (3,4-HP) chelator has been studied in terms of its physico-chemical and in vivo properties aimed at potential application as probe for nuclear imaging. In particular, based on spectrophotometric titrations, the hexa-coordinated (1:1) gallium complex appeared as the major species in a wide physiological acid-neutral pH range and its high stability (pGa=27.5) should avoid drug-induced toxicity resulting from Ga(III) accumulation in tissues due to processes of transmetallation with endogenenous ligands or demetallation. A multinuclear ((1)H and (71)Ga) NMR study gave some insights into the structure and dynamics of the gallium(III) chelate in solution, which are consistent with the tris-(3,4-HP) coordination and an eventual pseudo-octahedral geometry. Biodistribution and scintigraphic studies of the (67)Ga(III) labelled chelate, performed in Wistar rats, confirmed the in vivo stability of the radiolabelled complex, its non interaction with blood proteins and its quick renal clearance. These results indicate good perspectives for potential application of extrafunctionalized analogues in radiodiagnostic techniques. Copyright © 2010 Elsevier Inc. All rights reserved.

Developing and regenerating a sense of taste

PubMed Central

Barlow, Linda A.; Klein, Ophir D.

2015-01-01

Taste is one of the fundamental senses, and it is essential for our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Taste buds, which are clusters of neuroepithelial receptor cells, are housed in highly organized structures called taste papillae in the oral cavity. Whereas the overall structure of the taste periphery is conserved in almost all vertebrates examined to date, the anatomical, histological, and cell biological, as well as potentially the molecular details of taste buds in the oral cavity are diverse across species and even among individuals. In mammals, several types of gustatory papillae reside on the tongue in highly ordered arrangements, and the patterning and distribution of the mature papillae depends on coordinated molecular events in embryogenesis. In this review, we highlight new findings in the field of taste development, including how taste buds are patterned and how taste cell fate is regulated. We discuss whether a specialized taste bud stem cell population exists and how extrinsic signals can define which cell lineages are generated. We also address the question of whether molecular regulation of taste cell renewal is analogous to that of taste bud development. Finally, we conclude with suggestions for future directions, including the potential influence of the maternal diet and maternal health on the sense of taste in utero. PMID:25662267

Optimizing therapy of seizures in neurosurgery.

PubMed

Michelucci, Roberto

2006-12-26

The use of antiepileptic drugs (AEDs) in the neurosurgical setting has a number of implications, including their possible role in the prevention of seizures after acute cerebral insults or brain tumors and the potential for toxicity and interactions when these agents are administered in association with radiotherapy or chemotherapy. This review discusses these controversial issues and draws the following conclusions. 1) AEDs should be prescribed on a short-term basis to prevent seizures occurring within the first week after a cerebral insult (trauma, neurosurgical procedure) but are ineffective to avoid true post-traumatic epilepsy or first seizures in patients with primary or secondary cerebral neoplasms. 2) The use of phenytoin and, to a lesser extent, phenobarbital and carbamazepine during cranial irradiation is associated with an increased risk for severe, potentially fatal, mucocutaneous reactions. In this context, new AEDs with a very low potential for allergic cutaneous reactions should be preferred. 3) Enzyme-inducing AEDs, such as phenytoin, phenobarbital, and carbamazepine, may increase the clearance and reduce the clinical efficacy of corticosteroids and anticancer agents that are also metabolized by the cytochrome P450 system. The newly developed AEDs that are devoid of hepatic metabolism, such as levetiracetam and gabapentin, are now recommended because of good results in preliminary studies and because they do not show interactions with anticancer agents.

An in silico algal toxicity model with a wide applicability potential for industrial chemicals and pharmaceuticals.

PubMed

Önlü, Serli; Saçan, Melek Türker

2017-04-01

The authors modeled the 72-h algal toxicity data of hundreds of chemicals with different modes of action as a function of chemical structures. They developed mode of action-based local quantitative structure-toxicity relationship (QSTR) models for nonpolar and polar narcotics as well as a global QSTR model with a wide applicability potential for industrial chemicals and pharmaceuticals. The present study rigorously evaluated the generated models, meeting the Organisation for Economic Co-operation and Development principles of robustness, validity, and transparency. The proposed global model had a broad structural coverage for the toxicity prediction of diverse chemicals (some of which are high-production volume chemicals) with no experimental toxicity data. The global model is potentially useful for endpoint predictions, the evaluation of algal toxicity screening, and the prioritization of chemicals, as well as for the decision of further testing and the development of risk-management measures in a scientific and regulatory frame. Environ Toxicol Chem 2017;36:1012-1019. © 2016 SETAC. © 2016 SETAC.

Real-time obstacle avoidance using harmonic potential functions

NASA Technical Reports Server (NTRS)

Kim, Jin-Oh; Khosla, Pradeep K.

1992-01-01

This paper presents a new formulation of the artificial potential approach to the obstacle avoidance problem for a mobile robot or a manipulator in a known environment. Previous formulations of artificial potentials for obstacle avoidance have exhibited local minima in a cluttered environment. To build an artificial potential field, harmonic functions that completely eliminate local minima even for a cluttered environment are used. The panel method is employed to represent arbitrarily shaped obstacles and to derive the potential over the whole space. Based on this potential function, an elegant control strategy is proposed for the real-time control of a robot. The harmonic potential, the panel method, and the control strategy are tested with a bar-shaped mobile robot and a three-degree-of-freedom planar redundant manipulator.

Phenobarbital Treatment at a Neonatal Age Results in Decreased Efficacy of Omeprazole in Adult Mice.

PubMed

Tien, Yun-Chen; Piekos, Stephanie C; Pope, Chad; Zhong, Xiao-Bo

2017-03-01

Drug-drug interactions (DDIs) occur when the action of one drug interferes with or alters the activity of another drug taken concomitantly. This can lead to decreased drug efficacy or increased toxicity. Because of DDIs, physicians in the clinical practice attempt to avoid potential interactions when multiple drugs are coadministrated; however, there is still a large knowledge gap in understanding how drugs taken in the past can contribute to DDIs in the future. The goal of this study was to investigate the consequence of neonatal drug exposure on efficacy of other drugs administered up through adult life. We selected a mouse model to test phenobarbital exposure at a neonatal age and its impact on efficacy of omeprazole in adult life. The results of our experiment show an observed decrease in omeprazole's ability to raise gastric pH in adult mice that received single or multiple doses of phenobarbital at a neonatal age. This effect may be associated with the permanent induction of cytochrome P450 enzymes in adult liver after neonatal phenobarbital treatment. Our data indicates that DDIs may result from drugs administered in the past in an animal model and should prompt re-evaluation of how DDIs are viewed and how to avoid long-term DDIs in clinical practice. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

TOWARDS REFINED USE OF TOXICITY DATA IN ...

EPA Pesticide Factsheets

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants. In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

Land Application of Wastes: An Educational Program. Potentially Toxic Elements - Module 11.

ERIC Educational Resources Information Center

Clarkson, W. W.; And Others

Five elements are identified as being potentially hazardous in this module. These are boron, cadmium, copper, molybdenum, and nickel. The hazards to plants and animals posed by these elements are discussed in some detail. The sources of toxic elements in sewage and the factors that effect the uptake of toxic elements by sewage sludge are also…

Effectiveness of piscicides for controlling round gobies (Neogobius melanostomus)

USGS Publications Warehouse

Schreier, Theresa M.; Dawson, V.K.; Larson, W.

2008-01-01

Round gobies (Neogobius melanostomus) were introduced to the Great Lakes presumably as a result of ballast water releases from seagoing freighters returning from European water bodies. These unwelcome fish have become established in the Great Lakes region and are expanding their range to suitable portions of other interior drainage basins including the Mississippi River traversing the central United States and the Trent-Severn waterway spanning south-central Ontario. If the invasion continues, use of chemical toxicants as a control measure may be necessary. Toxicity tests of the currently registered piscicides antimycin, rotenone, 3-trifluoromethyl-4-nitrophenol (TFM), and Bayluscide?? were conducted with three fish species native to the Great Lakes and round gobies collected from the Illinois Waterway. Tests indicated that round gobies are sensitive to all of the piscicides, however, the level of sensitivity is similar to that of the native fish species tested. Therefore, currently registered piscicides have limited potential to selectively remove round gobies. Bottom-release formulations of Bayluscide?? and antimycin were also evaluated as control agents for the normally bottom-dwelling round goby. Avoidance behavior tests demonstrated that the round goby did not react to the presence of either chemical. Therefore, the bottom-release formulations may have some application for the selective removal of round gobies, and may be one of the few tools presently available to fishery managers to help limit the range expansion of this invasive fish.

[Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy].

PubMed

Troussier, I; Huguet, F; Servagi-Vernat, S; Benahim, C; Khalifa, J; Darmon, I; Ortholan, C; Krebs, L; Dejean, C; Fenoglietto, P; Vieillot, S; Bensadoun, R-J; Thariat, J

2015-04-01

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Inhibition and enhancement of microbial surface colonization: the role of silicate composition

USGS Publications Warehouse

Roberts, Jennifer A.

2004-01-01

Classical treatment of cell attachment by models of filtration or coulombic attraction assumes that attachment of cells to mineral surfaces would be controlled by factors such as response to predation, collision efficiency, or coulombic attraction between the charged groups at the mineral and cell surfaces. In the study reported here, the passive model of attachment was investigated using a native microbial consortium and a variety of Al- and Fe-bearing silicates and oxides to determine if other controls, such as mineral composition, also influence the interaction between cells and surfaces. Results from in situ colonization studies in an anaerobic groundwater at pH 6.8 combined with most probable number analyses (MPN) of surface-adherent cells demonstrate that electrostatic effects dominate microbial colonization on positively charged oxide surfaces regardless of mineral composition. In contrast, on negatively charged silicate minerals and glasses, the solid phase composition is a factor in determining the extent of microbial colonization, as well as the diversity of the attached community. In particular, silicates containing more than 1.2% Al exhibit less biomass than Al-poor silicates and MPN suggests a shift in community diversity, possibly indicating Al toxicity on these surfaces. When Fe is present in the silicate, however, this trend is reversed and abundant colonization of the surface is observed. Here, microorganisms preferentially colonize those silicate surfaces that offer beneficial nutrients and avoid those that contain potentially toxic elements.

Modification in digestive processing strategies to reduce toxic trace metal uptake in a marine bivalve

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

Decho, A.W.; Luoma, S.N.

1994-12-31

Bivalves possess two major digestion pathways for processing food particles: a rapid ``intestinal`` pathway where digestion is largely extracellular; and a slower ``glandular`` pathway where digestion is largely intracellular. The slower glandular pathway often results in more efficient absorption of carbon but also more efficient uptake of certain metals (e.g. Cr associated with bacteria). In the bivalve Potamocorbula amurensis, large portions (> 90%) of bacteria are selectively routed to the glandular pathway. This results in efficient C uptake but also efficient uptake of associated Cr. The authors further determined if prolonged exposure to Cr-contaminated bacteria would result in high Crmore » uptake by animals or whether mechanisms exist to reduce Cr exposure and uptake. Bivalves were exposed to natural food + added bacteria (with or without added Cr) for a 6-day period, then pulse-chase experiments were conducted to quantify digestive processing and % absorption efficiencies (%AE) of bacterial Cr. Bivalves compensate at low (2--5 ug/g sed) Cr by reducing overall food ingestion, while digestive processing of food remains statistically similar to controls. At high Cr (200--500 ug/g sed) there are marked decreases in % bacteria processed by glandular digestion. This results in lower overall %AE of Cr. The results suggest that bivalves under natural conditions might balance efficient carbon sequestration against avoiding uptake of potentially toxic metals associated the food.« less

Increased intrapulmonary retention of radiolabeled neutrophils in early oxygen toxicity

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

Rinaldo, J.E.; English, D.; Levine, J.

1988-02-01

Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria.more » However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.« less

Toxicity of clove essential oil and its ester eugenyl acetate against Artemia salina.

PubMed

Cansian, R L; Vanin, A B; Orlando, T; Piazza, S P; Puton, B M S; Cardoso, R I; Gonçalves, I L; Honaiser, T C; Paroul, N; Oliveira, D

2017-03-01

The production of compounds via enzymatic esterification has great scientific and technological interest due to the several inconveniences related to acid catalysis, mainly by these systems do not fit to the concept of "green chemistry". Besides, natural products as clove oil present compounds with excellent biological potential. Bioactives compounds are often toxic at high doses. The evaluation of lethality in a less complex animal organism can be used to a monitoring simple and rapid, helping the identification of compounds with potential insecticide activity against larvae of insect vector of diseases. In this sense, the toxicity against Artemia salina of clove essential oil and its derivative eugenyl acetate obtained by enzymatic esterification using Novozym 435 as biocatalyst was evaluated. The conversion of eugenyl acetate synthesis was 95.6%. The results about the evaluation of toxicity against the microcrustacean Artemia salina demonstrated that both oil (LC50= 0.5993 µg.mL-1) and ester (LC50= 0.1178 µg.mL-1) presented high toxic potential, being the eugenyl acetate almost 5 times more toxic than clove essential oil. The results reported here shows the potential of employing clove oil and eugenyl acetate in insecticide formulations.

The Flipside of the Power of Engineered T Cells: Observed and Potential Toxicities of Genetically Modified T Cells as Therapy.

PubMed

Bedoya, Felipe; Frigault, Matthew J; Maus, Marcela V

2017-02-01

Autologous T cells modified to recognize novel antigen targets are a novel form of therapy for cancer. We review the various potential forms of observed and hypothetical toxicities associated with genetically modified T cells. Despite the focus on toxicities in this review, re-directed T cells represent a powerful and highly effective form of anti-cancer therapy; we remain optimistic that the common toxicities will become routinely manageable and that some theoretical toxicity will be exceedingly rare, if ever observed. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Cost justification of clinical pharmacy services on a general surgery team: focus on diagnosis-related group cases.

PubMed

Bertch, K E; Hatoum, H T; Willett, M S; Witte, K W

1988-11-01

We used a novel approach to cost-justify clinical pharmacy services on a general surgery team in nine diagnosis-related group cases. The clinical pharmacist monitored nine patients longitudinally on a general surgery team from admission to discharge and intervened in their therapeutic management. Each recommendation was analyzed for rationale, acceptance, perceived impact on quality and/or cost of patient care, whether self-initiated or solicited, and impact on patient outcome. Types of recommendations and outcomes were categorized by process and outcome measurement criteria. Total cost avoidance per patient was calculated using costs of drug therapy, laboratory tests, and length of stay. Accounting for cost of clinical pharmacy services, net cost avoidance per patient was calculated. The clinical pharmacist made 101 recommendations on nine patients. Physicians accepted 82 percent of the recommendations; 77 percent of the recommendations were self-initiated and 23 percent were solicited. Recommendations had a perceived impact on cost, quality, or both at 13, 31, and 56 percent, respectively. Most recommendations (79 percent) brought patient therapy to a level of conformance with current standards of practice as documented in the medical literature. Recommendations that potentially preserved a major organ function by preventing drug-induced toxicity or the exacerbation of existing problems constituted 16 percent of the total. None of the accepted recommendations adversely affected patient outcome and 23 percent directly resulted in a measurable positive outcome in patient care. A total of four hospital days was potentially saved for two cases. Based on objective outcome criteria, a 1.9-day increase in therapeutic control was documented per patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Can plastic bag derived-microplastics act as vectors for metal exposure in terrestrial invertebrates?

NASA Astrophysics Data System (ADS)

E Hodson, Mark; Duffus-Hodson, Calum A.; Prendergast-Miller, Miranda; Thorpe, Karen

2017-04-01

Microplastics are widely reported contaminants in marine and freshwater ecosystems and studies have shown that they can be ingested by aquatic organisms and lead to potential negative effects on health. The effects can arise from the physical effects of the plastics (e.g. food displacement and blockages of the digestive tract) and from their potential to adsorb contaminants, primarily organic compounds, resulting in an increased exposure of the organism to toxic contaminants. Studies are beginning to emerge that also show a high abundance of microplastics in the terrestrial environment but there remains a lack of data on the impacts of these terrestrial microplastics or their interaction with other terrestrial pollutants. We conducted Zn adsorption experiments using HDPE microplastics, derived from plastic bags. Zinc adsorption to microplastics was similar to that observed in soils, but in the presence of both soil and microplastics, preferential adsorption onto the soil was observed. In desorption experiments, desorption of Zn from microplastics and soils was minimal (< 10 %) in 0.01 M CaCl2 solution, but in synthetic earthworm guts desorption of 40 - 60% was observed for the microplastics compared to 2 - 15 % for the soils. In earthworm exposure experiments Lumbricus terrestris earthworms cultivated in soils containing 0.35% by mass of Zn-bearing plastic (236 - 4505 mg kg-1) ingested the microplastics with no evidence for either preferential feeding or avoidance. There was no evidence for an accumulation of the microplastics in the earthworm gut or for signs of toxicity. Our experiments demonstrate that earthworms will ingest microplastics and that microplastics can adsorb metals and act as vectors for metal exposure in soil invertebrates. However, for Zn, the risk associated with this exposure appears to be minimal.

The NQO1 bioactivatable drug, β-lapachone, alters the redox state of NQO1+ pancreatic cancer cells, causing perturbation in central carbon metabolism.

PubMed

Silvers, Molly A; Deja, Stanislaw; Singh, Naveen; Egnatchik, Robert A; Sudderth, Jessica; Luo, Xiuquan; Beg, Muhammad S; Burgess, Shawn C; DeBerardinis, Ralph J; Boothman, David A; Merritt, Matthew E

2017-11-03

Many cancer treatments, such as those for managing recalcitrant tumors like pancreatic ductal adenocarcinoma, cause off-target toxicities in normal, healthy tissue, highlighting the need for more tumor-selective chemotherapies. β-Lapachone is bioactivated by NAD(P)H:quinone oxidoreductase 1 (NQO1). This enzyme exhibits elevated expression in most solid cancers and therefore is a potential cancer-specific target. β-Lapachone's therapeutic efficacy partially stems from the drug's induction of a futile NQO1-mediated redox cycle that causes high levels of superoxide and then peroxide formation, which damages DNA and causes hyperactivation of poly(ADP-ribose) polymerase, resulting in extensive NAD + /ATP depletion. However, the effects of this drug on energy metabolism due to NAD + depletion were never described. The futile redox cycle rapidly consumes O 2 , rendering standard assays of Krebs cycle turnover unusable. In this study, a multimodal analysis, including metabolic imaging using hyperpolarized pyruvate, points to reduced oxidative flux due to NAD + depletion after β-lapachone treatment of NQO1+ human pancreatic cancer cells. NAD + -sensitive pathways, such as glycolysis, flux through lactate dehydrogenase, and the citric acid cycle (as inferred by flux through pyruvate dehydrogenase), were down-regulated by β-lapachone treatment. Changes in flux through these pathways should generate biomarkers useful for in vivo dose responses of β-lapachone treatment in humans, avoiding toxic side effects. Targeting the enzymes in these pathways for therapeutic treatment may have the potential to synergize with β-lapachone treatment, creating unique NQO1-selective combinatorial therapies for specific cancers. These findings warrant future studies of intermediary metabolism in patients treated with β-lapachone. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Effects of pesticides and plant bio-stimulants on the germination of chlamydospores and in vitro development of the nematophagous fungus Pochonia chlamydosporia].

PubMed

Ceiro, Wilson G; Arévalo, Jersys; Hidalgo-Díaz, Leopoldo

2015-01-01

The effects of pesticides and plant bio-stimulants used in protected vegetable production systems on the fungus Pochonia chlamydosporia are unknown. The effectiveness of P. chlamydosporia against Meloidogyne spp. could be affected by products used in protected vegetable production systems. Two in vitro assays were carried out to evaluate any potential effect that pesticides and bio-stimulants often used in these systems could have on the fungus. The effect on chlamydospore germination was evaluated in a first assay, and mycelia growth and sporulation in a second. With these results, the compatibility of each product with the fungus was determined. Chlamydospores germination was over 50% with the control, FitoMas E, Biobras-16 and Amidor. Lower results were observed with other products, with some of them even inhibiting germination completely. Fungal growth was potentiated by Biobras-16 to 106.23%, promoted up to 50-100% by the control, FitoMas E and Cuproflow, and was below 50% with the rest of the products.Cipermetrina, Benomilo, Zineb, Mitigan, Karate, FitoMas E and Amidor promoted fungal sporulation, which was below 50% with Cuproflow and completely inhibited by the other products. Fifty-four percent of the products evaluated were compatible with P. chlamydosporia, while 8% were toxic and 38%, very toxic. Cipermetrina, Karate, Amidor, Benomilo, Zineb, Mitigan and FitoMas E were compatible with P. chlamydosporia. If it is necessary to use any of the other products for integrated pest management in protected vegetable production systems, it is recommended to avoid direct contact with P. chlamydosporia. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Auger Emitting Radiopharmaceuticals for Cancer Therapy

NASA Astrophysics Data System (ADS)

Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

Root based responses account for Psidium guajava survival at high nickel concentration.

PubMed

Bazihizina, Nadia; Redwan, Mirvat; Taiti, Cosimo; Giordano, Cristiana; Monetti, Emanuela; Masi, Elisa; Azzarello, Elisa; Mancuso, Stefano

2015-02-01

The presence of Psidium guajava in polluted environments has been reported in recent studies, suggesting that this species has a high tolerance to the metal stress. The present study aims at a physiological characterization of P. guajava response to high nickel (Ni) concentrations in the root-zone. Three hydroponic experiments were carried out to characterize the effects of toxic Ni concentrations on morphological and physiological parameters of P. guajava, focusing on Ni-induced damages at the root-level and root ion fluxes. With up to 300μM NiSO4 in the root-zone, plant growth was similar to that in control plants, whereas at concentrations higher than 1000μM NiSO4 there was a progressive decline in plant growth and leaf gas exchange parameters; this occurred despite, at all considered concentrations, plants limited Ni(2+) translocation to the shoot, therefore avoiding shoot Ni(2+) toxicity symptoms. Maintenance of plant growth with 300μM Ni(2+) was associated with the ability to retain K(+) in the roots meanwhile 1000 and 3000μM NiSO4 led to substantial K(+) losses. In this study, root responses mirror all plant performances suggesting a direct link between root functionality and Ni(2+) tolerance mechanisms and plant survival. Considering that Ni was mainly accumulated in the root system, the potential use of P. guajava for Ni(2+) phytoextraction in metal-polluted soils is limited; nevertheless, the observed physiological changes indicate a good Ni(2+) tolerance up to 300μM NiSO4 suggesting a potential role for the phytostabilization of polluted soils. Copyright © 2014 Elsevier GmbH. All rights reserved.

Oxygen diffusion: an enzyme-controlled variable parameter.

PubMed

Erdmann, Wilhelm; Kunke, Stefan

2014-01-01

Previous oxygen microelectrode studies have shown that the oxygen diffusion coefficient (DO₂) increases during extracellular PO₂ decreases, while intracellular PO₂ remained unchanged and thus cell function (spike activity of neurons). Oxygen dependency of complex multicellular organisms requires a stable and adequate oxygen supply to the cells, while toxic concentrations have to be avoided. Oxygen brought to the tissue by convection diffuses through the intercellular and cell membranes, which are potential barriers to diffusion. In gerbil brain cortex, PO₂ and DO₂ were measured by membrane-covered and by bare gold microelectrodes, as were also spike potentials. Moderate respiratory hypoxia was followed by a primary sharp drop of tissue PO₂ that recovered to higher values concomitant with an increase of DO₂. A drop in intracellular PO₂ recovered immediately. Studies on the abdominal ganglion of aplysia californica showed similar results.Heterogeneity is a feature of both normal oxygen supply to tissue and supply due to a wide range of disturbances in oxygen supply. Oxygen diffusion through membranes is variable thereby ensuring adequate intracellular PO₂. Cell-derived glucosamine oxidase seems to regulate the polymerization/depolymerisation ratio of membrane mucopolysaccharides and thus oxygen diffusion.Variability of oxygen diffusion is a decisive parameter for regulating the supply/demand ratio of oxygen supply to the cell; this occurs in highly developed animals as well as in species of a less sophisticated nature. Autoregulation of oxygen diffusion is as important as the distribution/perfusion ratio of the capillary meshwork and as the oxygen extraction ratio in relation to oxygen consumption of the cell. Oxygen diffusion resistance is the cellular protection against luxury oxygen supply (which can result in toxic oxidative species leading to mutagenesis).

Life cycle environmental impacts of domestic solar water heaters in Turkey: The effect of different climatic regions.

PubMed

Uctug, Fehmi Gorkem; Azapagic, Adisa

2018-05-01

Solar water heating (SWH) systems could help reduce environmental impacts from energy use but their performance and impacts depend on the climate. This paper considers how these vary for residential SWH across four different climatic regions in Turkey, ranging from hot to cold climates. Life cycle assessment was used for these purposes. The results suggest that in the hotter regions, the impacts of SWH are 1.5-2 times lower than those of natural gas boilers. A similar trend was observed in the two colder regions except for acidification, which was four times higher than that of the boiler. The raw materials and electricity required for the manufacturing of the systems were found to be the most important contributors to the impacts. Recycling the major components instead of landfilling reduced human toxicity potential by 50% but had only a small effect (5%) on the other impacts. The impacts were highly sensitive to the type of material used for the construction of the hot storage tank, but were not affected by transport and end-of life recycling. The only exception to the latter is human toxicity potential which decreased significantly with greater recycling. Extrapolating the results at the national level showed that SWH systems could reduce the annual greenhouse gas emissions in Turkey by 790kt CO 2 -eq. and would save the economy $162.5millionperyear through the avoided imports of natural gas. All other impacts would also be reduced significantly (3-32 times), except for acidification which would double. Therefore, SWH systems should be deployed more extensively in Turkey but government incentives may be needed to stimulate the uptake. Copyright © 2017 Elsevier B.V. All rights reserved.

Iron-Catalyzed C-O Bond Activation: Opportunity for Sustainable Catalysis.

PubMed

Bisz, Elwira; Szostak, Michal

2017-10-23

Oxygen-based electrophiles have emerged as some of the most valuable cross-coupling partners in organic synthesis due to several major strategic and environmental benefits, such as abundance and potential to avoid toxic halide waste. In this context, iron-catalyzed C-O activation/cross-coupling holds particular promise to achieve sustainable catalytic protocols due to its natural abundance, inherent low toxicity, and excellent economic and ecological profile. Recently, tremendous progress has been achieved in the development of new methods for functional-group-tolerant iron-catalyzed cross-coupling reactions by selective C-O cleavage. These methods establish highly attractive alternatives to traditional cross-coupling reactions by using halides as electrophilic partners. In particular, new easily accessible oxygen-based electrophiles have emerged as substrates in iron-catalyzed cross-coupling reactions, which significantly broaden the scope of this catalysis platform. New mechanistic manifolds involving iron catalysis have been established; thus opening up vistas for the development of a wide range of unprecedented reactions. The synthetic potential of this sustainable mode of reactivity has been highlighted by the development of new strategies in the construction of complex motifs, including in target synthesis. The most recent advances in sustainable iron-catalyzed cross-coupling of C-O-based electrophiles are reviewed, with a focus on both mechanistic aspects and synthetic utility. It should be noted that this catalytic manifold provides access to motifs that are often not easily available by other methods, such as the assembly of stereodefined dienes or C(sp 2 )-C(sp 3 ) cross-couplings, thus emphasizing the synthetic importance of this mode of reactivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Necessity of toxicity assessment in Turkish industrial discharges (examples from metal and textile industry effluents).

PubMed

Sponza, Delia Teresa

2002-01-01

Toxicity of some organic and inorganic chemicals to microorganisms is an important consideration in assessing their environmental impact against their economic benefits. Microorganisms play an important role in several environmental processes, both natural and engineered. Some organic and inorganics at toxic levels have been detected in industrial discharges resulting in plant upsets and discharge permit violations. In addition to this, even though in some cases the effluent wastewater does not exceed the discharge limits, the results of toxicity tests show potential toxicity. Toxicity knowledge of effluents can benefit treatment plant operators in optimising plant operation, setting pre-treatment standards, and protecting receiving water quality and in establishing sewer discharge permits to safeguard the plant. In the Turkish regulations only toxicity dilution factor (TDF) with fish is part of the toxicity monitoring program of permissible wastewater discharge. In various countries, laboratory studies involving the use of different organisms and protocol for toxicity assessment was conducted involving a number of discharges. In this study, it was aimed to investigate the acute toxicity of textile and metal industry wastewaters by traditional and enrichment toxicity tests and emphasize the importance of toxicity tests in wastewater discharge regulations. The enrichment toxicity tests are novel applications and give an idea whether there is potential toxicity or growth limiting and stimulation conditions. Different organisms were used such as bacteria (Floc and Coliform bacteria) algae (Chlorella sp.). fish (Lepistes sp.) and protozoan (Vorticella sp.) to represent four tropic levels. The textile industry results showed acute toxicity for at least one organism in 8 out of 23 effluent samples. Acute toxicity for at least two organisms in 7 out of 23 effluent sampling was observed for the metal industry. The toxicity test results were assessed with chemical analyses such as COD, BOD, color and heavy metals. It was observed that the toxicity of the effluents could not be explained by using physicochemical analyses in 5 cases for metal and 4 cases for the textile industries. The results clearly showed that the use of bioassay tests produce additional information about the toxicity potential of industrial discharges and effluents.

Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Nanoparticle Titanium Dioxide

EPA Science Inventory

Identification of toxicity pathways linked to chemical -exposure is critical for a better understanding of biological effects of the exposure, toxic mechanisms, and for enhancement of the prediction of chemical toxicity and adverse health outcomes. To identify toxicity pathways a...

Research on UAV Intelligent Obstacle Avoidance Technology During Inspection of Transmission Line

NASA Astrophysics Data System (ADS)

Wei, Chuanhu; Zhang, Fei; Yin, Chaoyuan; Liu, Yue; Liu, Liang; Li, Zongyu; Wang, Wanguo

Autonomous obstacle avoidance of unmanned aerial vehicle (hereinafter referred to as UAV) in electric power line inspection process has important significance for operation safety and economy for UAV intelligent inspection system of transmission line as main content of UAV intelligent inspection system on transmission line. In the paper, principles of UAV inspection obstacle avoidance technology of transmission line are introduced. UAV inspection obstacle avoidance technology based on particle swarm global optimization algorithm is proposed after common obstacle avoidance technologies are studied. Stimulation comparison is implemented with traditional UAV inspection obstacle avoidance technology which adopts artificial potential field method. Results show that UAV inspection strategy of particle swarm optimization algorithm, adopted in the paper, is prominently better than UAV inspection strategy of artificial potential field method in the aspects of obstacle avoidance effect and the ability of returning to preset inspection track after passing through the obstacle. An effective method is provided for UAV inspection obstacle avoidance of transmission line.

Life-cycle-assessment of the historical development of air pollution control and energy recovery in waste incineration.

PubMed

Damgaard, Anders; Riber, Christian; Fruergaard, Thilde; Hulgaard, Tore; Christensen, Thomas H

2010-07-01

Incineration of municipal solid waste is a debated waste management technology. In some countries it is the main waste management option whereas in other countries it has been disregarded. The main discussion point on waste incineration is the release of air emissions from the combustion of the waste, but also the energy recovery efficiency has a large importance. The historical development of air pollution control in waste incineration was studied through life-cycle-assessment modelling of eight different air pollution control technologies. The results showed a drastic reduction in the release of air emissions and consequently a significant reduction in the potential environmental impacts of waste incineration. Improvements of a factor 0.85-174 were obtained in the different impact potentials as technology developed from no emission control at all, to the best available emission control technologies of today (2010). The importance of efficient energy recovery was studied through seven different combinations of heat and electricity recovery, which were modelled to substitute energy produced from either coal or natural gas. The best air pollution control technology was used at the incinerator. It was found that when substituting coal based energy production total net savings were obtained in both the standard and toxic impact categories. However, if the substituted energy production was based on natural gas, only the most efficient recovery options yielded net savings with respect to the standard impacts. With regards to the toxic impact categories, emissions from the waste incineration process were always larger than those from the avoided energy production based on natural gas. The results shows that the potential environmental impacts from air emissions have decreased drastically during the last 35 years and that these impacts can be partly or fully offset by recovering energy which otherwise should have been produced from fossil fuels like coal or natural gas. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

α1-Adrenoceptors in the hippocampal dentate gyrus involved in learning-dependent long-term potentiation during active-avoidance learning in rats.

PubMed

Lv, Jing; Zhan, Su-Yang; Li, Guang-Xie; Wang, Dan; Li, Ying-Shun; Jin, Qing-Hua

2016-11-09

The hippocampus is the key structure for learning and memory in mammals and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. The influences of norepinephrine (NE) on the modulation of learning and memory, as well as LTP, through β-adrenoceptors are well documented, whereas the role of α1-adrenoceptors in learning-dependent LTP is not yet clear. In the present study, we measured extracellular concentrations of NE in the hippocampal dentate gyrus (DG) region using an in-vivo brain microdialysis and high-performance liquid chromatography techniques during the acquisition and extinction of active-avoidance behavior in freely moving conscious rats. Next, the effects of prazosin (an antagonist of α1-adrenoceptor) and phenylephrine (an agonist of the α1-adrenoceptor) on amplitudes of field excitatory postsynaptic potential were measured in the DG region during the active-avoidance behavior. Our results showed that the extracellular concentration of NE in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to the baseline level following extinction training. A local microinjection of prazosin into the DG significantly accelerated the acquisition of the active-avoidance behavior, whereas a local microinjection of phenylephrine retarded the acquisition of the active-avoidance behavior. Furthermore, in all groups, the changes in field excitatory postsynaptic potential amplitude were accompanied by corresponding changes in active-avoidance behavior. Our results suggest that NE activation of α1-adrenoceptors in the hippocampal DG inhibits active-avoidance learning by modulation of synaptic efficiency in rats.

Integration of genomic endpoints into toxicity identification evaluations

EPA Science Inventory

Toxicity identification and evaluations (TIEs) use physical/chemical manipulation of a sample to isolate or change the potency of different groups of toxicants potentially present in a sample. Organisms are then exposed to these fractions to determine if their toxicity has change...

Synthetic Neurotensin Analogues Are Nontoxic Analgesics for the Rabbit Cornea

PubMed Central

Kim, Charles; Barbut, Denise; Heinemann, Murk H.; Pasternak, Gavril; Rosenblatt, Mark I.

2014-01-01

Purpose. To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Methods. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. Results. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Conclusions. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. PMID:24825106

Estimation of potential safety benefits for pedestrian crash avoidance/mitigation systems.

DOT National Transportation Integrated Search

2017-04-01

This report presents and exercises a methodology to estimate the effectiveness and potential safety benefits of production pedestrian crash avoidance/mitigation systems. The analysis focuses on light vehicles moving forward and striking a pedestrian ...

Parameter uncertainty and variability in evaluative fate and exposure models

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

Hertwich, E.G.; McKone, T.E.; Pease, W.S.

The human toxicity potential, a weighting scheme used to evaluate toxic emissions for life cycle assessment and toxics release inventories, is based on potential dose calculations and toxicity factors. This paper evaluates the variance in potential dose calculations that can be attributed to the uncertainty in chemical-specific input parameters as well as the variability in exposure factors and landscape parameters. A knowledge of the uncertainty allows us to assess the robustness of a decision based on the toxicity potential; a knowledge of the sources of uncertainty allows one to focus resources if the uncertainty is to be reduced. The potentialmore » does of 236 chemicals was assessed. The chemicals were grouped by dominant exposure route, and a Monte Carlo analysis was conducted for one representative chemical in each group. The variance is typically one to two orders of magnitude. For comparison, the point estimates in potential dose for 236 chemicals span ten orders of magnitude. Most of the variance in the potential dose is due to chemical-specific input parameters, especially half-lives, although exposure factors such as fish intake and the source of drinking water can be important for chemicals whose dominant exposure is through indirect routes. Landscape characteristics are generally of minor importance.« less

Comparison of Modeling Approaches to Prioritize Chemicals Based on Estimates of Exposure and Exposure Potential

EPA Science Inventory

While only limited data are available to characterize the potential toxicity of over 8 million commercially available chemical substances, there is even less information available on the exposure and use-scenarios that are required to link potential toxicity to human and ecologic...

One-pot synthesis of water soluble iron nanoparticles using rationally-designed peptides and ligand release.

PubMed

Papst, Stefanie; Cheong, Soshan; Banholzer, Moritz J; Brimble, Margaret A; Williams, David E; Tilley, Richard D

2013-05-18

Herein we report the rational design of new phosphopeptides for control of nucleation, growth and aggregation of water-soluble, superparamagnetic iron-iron oxide core-shell nanoparticles. The use of the designed peptides enables a one-pot synthesis that avoids utilizing unstable or toxic iron precursors, organic solvents, and the need for exchange of capping agent after synthesis of the NPs.

Surgery of the Forestomach.

PubMed

Lozier, Joseph W; Niehaus, Andrew J

2016-11-01

Indications for rumen surgery include rumen tympany (bloat), toxic plant ingestion, to provide enteral nutrition, to perform elective cannula placement, and to access other forestomach compartments (reticulum/omasum). The rumen is a highly contaminated viscus and special care should be taken to avoid peritoneal contamination from rumen contents. Diseases causing forestomach dysfunction and surgical procedures on the forestomach compartments are discussed here. Copyright © 2016 Elsevier Inc. All rights reserved.

Aqueous dye-sensitized solar cell electrolytes based on the ferricyanide-ferrocyanide redox couple.

PubMed

Daeneke, Torben; Uemura, Yu; Duffy, Noel W; Mozer, Attila J; Koumura, Nagatoshi; Bach, Udo; Spiccia, Leone

2012-03-02

Solar energy conversion efficiencies of over 4% have been achieved in DSCs constructed with aqueous electrolytes based on the ferricyanide-ferrocyanide redox couple, thereby avoiding the use of expensive, flammable and toxic solvents. This paradigm shift was made possible by the use of a hydrophobic organic carbazole dye. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanomaterials and Retinal Toxicity

EPA Science Inventory

The neuroretina should be considered as a potential site of nanomaterial toxicity. Engineered nanomaterials may reach the retina through three potential routes of exposure including; intra­ vitreal injection of therapeutics; blood-borne delivery in the retinal vasculature an...

Arsenic: A Review of the Element's Toxicity, Plant Interactions, and Potential Methods of Remediation.

PubMed

Hettick, Bryan E; Cañas-Carrell, Jaclyn E; French, Amanda D; Klein, David M

2015-08-19

Arsenic is a naturally occurring element with a long history of toxicity. Sites of contamination are found worldwide as a result of both natural processes and anthropogenic activities. The broad scope of arsenic toxicity to humans and its unique interaction with the environment have led to extensive research into its physicochemical properties and toxic behavior in biological systems. The purpose of this review is to compile the results of recent studies concerning the metalloid and consider the chemical and physical properties of arsenic in the broad context of human toxicity and phytoremediation. Areas of focus include arsenic's mechanisms of human toxicity, interaction with plant systems, potential methods of remediation, and protocols for the determination of metals in experimentation. This assessment of the literature indicates that controlling contamination of water sources and plants through effective remediation and management is essential to successfully addressing the problems of arsenic toxicity and contamination.

NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning

PubMed Central

Chen, Ming; Wang, Quanxin; Zhang, Lixin; Yan, Guiying

2016-01-01

Fungal infection has become one of the leading causes of hospital-acquired infections with high mortality rates. Furthermore, drug resistance is common for fungus-causing diseases. Synergistic drug combinations could provide an effective strategy to overcome drug resistance. Meanwhile, synergistic drug combinations can increase treatment efficacy and decrease drug dosage to avoid toxicity. Therefore, computational prediction of synergistic drug combinations for fungus-causing diseases becomes attractive. In this study, we proposed similar nature of drug combinations: principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa. Furthermore, we developed a novel algorithm termed Network-based Laplacian regularized Least Square Synergistic drug combination prediction (NLLSS) to predict potential synergistic drug combinations by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures. We applied NLLSS to predict antifungal synergistic drug combinations and showed that it achieved excellent performance both in terms of cross validation and independent prediction. Finally, we performed biological experiments for fungal pathogen Candida albicans to confirm 7 out of 13 predicted antifungal synergistic drug combinations. NLLSS provides an efficient strategy to identify potential synergistic antifungal combinations. PMID:27415801

Energy Drinks: Implications for the Breastfeeding Mother.

PubMed

Thorlton, Janet; Ahmed, Azza; Colby, David A

2016-01-01

Breastfeeding women may experience disrupted sleep schedules and be tempted to turn to popular energy drinks to reduce fatigue and enhance alertness, prompting the question: What are the maternal and child health implications for breastfeeding mothers consuming energy drinks? Caffeine and vitamin-rich energy drinks contain a variety of herbal ingredients and vitamins; however, ingredient amounts may not be clearly disclosed on product labels. Interactions between herbal ingredients and caffeine are understudied and not well defined in the literature. Some infants can be sensitive to caffeine and display increased irritability and sleep disturbances when exposed to caffeine from breastmilk. Breastfeeding women who consume energy drinks may be ingesting herbal ingredients that have not undergone scientific evaluation, and if taking prenatal vitamins, may unknowingly exceed the recommended daily intake. Caffeinated products are marketed in newer ways, fueling concerns about health consequences of caffeine exposure. We present implications associated with consumption of caffeine and vitamin-rich energy drinks among breastfeeding women. Product safety, labeling, common ingredients, potential interactions, and clinical implications are discussed. Healthcare providers should encourage breastfeeding women to read product labels for ingredients, carbohydrate content, serving size, and to discourage consumption of energy drinks when breastfeeding and/or taking prenatal vitamins, to avoid potential vitamin toxicity.

Current toxicological aspects on drug and chemical transport and metabolism across the human placental barrier.

PubMed

Giaginis, Constantinos; Theocharis, Stamatios; Tsantili-Kakoulidou, Anna

2012-10-01

Placenta plays an obligatory role in fetal growth and development by performing a multitude of functions, including embryo implantation, transport of nutrients and elimination of metabolic waste products and endocrine activity. Drugs and chemicals can transfer across the placental barrier from mother to fetus either by passive diffusion mechanisms and/or via a network of active transporters, which may lead to potential fetotoxicity effects. Placenta also expresses a wide variety of enzymes, being capable of metabolizing a large diversity of drugs and chemicals to metabolites of lower or even higher toxicity than parent compounds. The present review aims to summarize the current toxicological aspects in the emerging topic of drug transport and metabolism across the human placental barrier. There is an emerging demand for accurate assessment of drug transport and metabolism across the human placental barrier, on the basis of a high throughput screening process in the early stages of drug design, to avoid drug candidates from potential fetotoxicity effects. In this aspect, combined studies, which take into account in vivo and in vitro investigations, as well as the ex vivo perfusion method and the recently developed computer-aided technologies, may significantly contribute to this direction.

Controlling off-label medication use.

PubMed

Gillick, Muriel R

2009-03-03

Off-label prescribing may lead to innovative new uses of old medications, is essential in such fields as pediatrics, and avoids the lengthy and expensive process of modifying U.S. Food and Drug Administration (FDA) drug labeling. Using medications for unapproved indications, however, raises concerns about patient safety when the drugs have a high potential for toxicity and generates economic concerns when their cost is high. A possible means of controlling the use of off-label drugs is to focus on medications used off-label that are both expensive and potentially risky. These are principally biotechnology drugs, such as recombinant enzymes, cytokines, and monoclonal antibodies. This article suggests a 2-step process for controlling use of such drugs, analogous to that used for devices. Once a drug is FDA approved, it would undergo scrutiny using the Centers for Medicare & Medicaid Services (CMS) National Coverage Determination method if its cost exceeds a specified benchmark-for example, $12 000, which is the average cost of a pacemaker. The CMS would pay only for off-label uses for which there is adequate evidence in its National Coverage Determination process. Other insurance companies would probably adopt the recommendations of CMS.

Modulation of mitochondrial metabolism as a biochemical trait in blood feeding organisms: the redox vampire hypothesis redux.

PubMed

Ferreira, Caroline M; Oliveira, Matheus P; Paes, Marcia C; Oliveira, Marcus F

2018-06-01

Hematophagous organisms undergo remarkable metabolic changes during the blood digestion process, increasing fermentative glucose metabolism, and reducing respiratory rates, both consequence of functional mitochondrial remodeling. Here, we review the pathways involved in energy metabolism and mitochondrial functionality in a comparative framework across different hematophagous species, and consider how these processes regulate redox homeostasis during blood digestion. The trend across distinct species indicate that a switch in energy metabolism might represent an important defensive mechanism to avoid the potential harmful interaction of oxidants generated from aerobic energy metabolism with products derived from blood digestion. Indeed, in insect vectors, blood feeding transiently reduces respiratory rates and oxidant production, irrespective of tissue and insect model. On the other hand, a different scenario is observed in several unrelated parasite species when exposed to blood digestion products, as respiratory rates reduce and mitochondrial oxidant production increase. The emerging picture indicates that re-wiring of energy metabolism, through reduced mitochondrial function, culminates in improved tolerance to redox insults and seems to represent a key step for hematophagous organisms to cope with the overwhelming and potentially toxic blood meal. © 2018 International Federation for Cell Biology.

Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

PubMed Central

Essack, Magbubah; Alzubaidy, Hanin S.; Bajic, Vladimir B.; Archer, John A. C.

2014-01-01

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review. PMID:25356733

Chemical compounds toxic to invertebrates isolated from marine cyanobacteria of potential relevance to the agricultural industry.

PubMed

Essack, Magbubah; Alzubaidy, Hanin S; Bajic, Vladimir B; Archer, John A C

2014-10-29

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

[Research progress of health effect of polybrominated diphenyl ethers].

PubMed

Zhai, J X; Tong, S L

2016-06-01

Polybrominated diphenyl ethers (PBDEs) was one of the most common brominated flame retardants, it has been widely used in products such as furnitures, polymer and plastical material, textiles, electronic products and building materials. PBDEs have potential effect such as neurodevelopmental toxicity, reproductive toxicity, thyroid toxicity, immunological toxicity, embryo toxicity, liver toxicity, teratogenicity and potential carcinogenicity. This paper was aimed to review the environmental exposure way, current level, neurotoxicity, neurodevelopmental toxicity and reproductive toxicity of PBDEs. In recent years, PBDEs has been detected in environment, wildlife animal and human body around the world, there were the significant differences of exposure levels of PBDEs. The most abundant congener were tetra-BDE or BDE-47, hexa-BDE or BDE-153, and deca-BDE or BDE-209. Prenatal exposure to PBDEs has great impact on the infants' neurodevelopmental function, induces changes in neuropsychological developmental behavior, decreases of congnition, motivation and attention. High levels of PBDEs have positive relationship with Luteinizing hormone levels, testis disfunction and children's cryptorchidism, and have negative relationship with sperm number and testis size.

Review of chemical, medication, and anesthesia toxicity in the OR.

PubMed

Fiedler, M A; Biddle, C

1998-02-01

A host of toxic substances exist in the OR. The toxicity of prep solutions, cleaning chemicals, common medications, and trace anesthetic gases varies greatly. Nurses use, direct others in the use of, or administer potential toxins while breathing air that may be contaminated to some degree with anesthetic vapors. Often, the OR nurse is the neighborhood resource when questions about the toxicity of common chemicals and drugs arise. A general knowledge of the toxicity of these substances improves the nurse's ability to assess the risk from trace anesthetic gases, prevent injury to patients, provide first aid when potentially dangerous exposure occurs, and direct others in the safe use of OR chemicals.

Evaluation of the Possible Sources and Controlling Factors of Toxic Metals/Metalloids in the Florida Everglades and Their Potential Risk of Exposure.

PubMed

Li, Yanbin; Duan, Zhiwei; Liu, Guangliang; Kalla, Peter; Scheidt, Daniel; Cai, Yong

2015-08-18

The Florida Everglades is an environmentally sensitive wetland ecosystem with a number of threatened and endangered fauna species susceptible to the deterioration of water quality. Several potential toxic metal sources exist in the Everglades, including farming, atmospheric deposition, and human activities in urban areas, causing concerns of potential metal exposure risks. However, little is known about the pollution status of toxic metals/metalloids of potential concern, except for Hg. In this study, eight toxic metals/metalloids (Cd, Cr, Pb, Ni, Cu, Zn, As, and Hg) in Everglades soils were investigated in both dry and wet seasons. Pb, Cr, As, Cu, Cd, and Ni were identified to be above Florida SQGs (sediment quality guidelines) at a number of sampling sites, particularly Pb, which had a level of potential risk to organisms similar to that of Hg. In addition, a method was developed for quantitative source identification and controlling factor elucidation of toxic metals/metalloids by introducing an index, enrichment factor (EF), in the conventional multiple regression analysis. EFs represent the effects of anthropogenic sources on metals/metalloids in soils. Multiple regression analysis showed that Cr and Ni were mainly controlled by anthropogenic loading, whereas soil characteristics, in particular natural organic matter (NOM), played a more important role for Hg, As, Cd, and Zn. NOM may control the distribution of these toxic metals/metalloids by affecting their mobility in soils. For Cu and Pb, the effects of EFs and environmental factors are comparable, suggesting combined effects of loading and soil characteristics. This study is the first comprehensive research with a vast amount of sampling sites on the distribution and potential risks of toxic metals/metalloids in the Everglades. The finding suggests that in addition to Hg other metals/metalloids could also potentially be an environmental problem in this wetland ecosystem.

Nanomaterial Toxicity Testing in the 21st Century: Use of a Predictive Toxicological Approach and High Throughput Screening

PubMed Central

NEL, ANDRE; XIA, TIAN; MENG, HUAN; WANG, XIANG; LIN, SIJIE; JI, ZHAOXIA; ZHANG, HAIYUAN

2014-01-01

Conspectus The production of engineered nanomaterials (ENMs) is a scientific breakthrough in material design and the development of new consumer products. While the successful implementation of nanotechnology is important for the growth of the global economy, we also need to consider the possible environmental health and safety (EHS) impact as a result of the novel physicochemical properties that could generate hazardous biological outcomes. In order to assess ENM hazard, reliable and reproducible screening approaches are needed to test the basic materials as well as nano-enabled products. A platform is required to investigate the potentially endless number of bio-physicochemical interactions at the nano/bio interface, in response to which we have developed a predictive toxicological approach. We define a predictive toxicological approach as the use of mechanisms-based high throughput screening in vitro to make predictions about the physicochemical properties of ENMs that may lead to the generation of pathology or disease outcomes in vivo. The in vivo results are used to validate and improve the in vitro high throughput screening (HTS) and to establish structure-activity relationships (SARs) that allow hazard ranking and modeling by an appropriate combination of in vitro and in vivo testing. This notion is in agreement with the landmark 2007 report from the US National Academy of Sciences, “Toxicity Testing in the 21st Century: A Vision and a Strategy” (http://www.nap.edu/catalog.php?record_id=11970), which advocates increased efficiency of toxicity testing by transitioning from qualitative, descriptive animal testing to quantitative, mechanistic and pathway-based toxicity testing in human cells or cell lines using high throughput approaches. Accordingly, we have implemented HTS approaches to screen compositional and combinatorial ENM libraries to develop hazard ranking and structure-activity relationships that can be used for predicting in vivo injury outcomes. This predictive approach allows the bulk of the screening analysis and high volume data generation to be carried out in vitro, following which limited, but critical, validation studies are carried out in animals or whole organisms. Risk reduction in the exposed human or environmental populations can then focus on limiting or avoiding exposures that trigger these toxicological responses as well as implementing safer design of potentially hazardous ENMs. In this communication, we review the tools required for establishing predictive toxicology paradigms to assess inhalation and environmental toxicological scenarios through the use of compositional and combinatorial ENM libraries, mechanism-based HTS assays, hazard ranking and development of nano-SARs. We will discuss the major injury paradigms that have emerged based on specific ENM properties, as well as describing the safer design of ZnO nanoparticles based on characterization of dissolution chemistry as a major predictor of toxicity. PMID:22676423

Influence of interspecific interactions on avoidance response to contamination.

PubMed

Silva, Daniel C V R; Araújo, Cristiano V M; Marassi, Rodrigo J; Cardoso-Silva, Sheila; Neto, Morun B; Silva, Gilmar C; Ribeiro, Rui; Silva, Flávio T; Paiva, Teresa C B; Pompêo, Marcelo L M

2018-06-17

An increasing number of studies have shown the ability of organisms to escape from toxic effects due to contamination, by moving spatially towards less contaminated habitats. However, this issue has been investigated in monospecific scenarios, without considering possible interactions between species during the contamination avoidance process. It is widely known that the spatial distribution of one species can be affected by another one, in different ways. Therefore, the main question addressed in the present study was as follows: Might interspecific interaction between the freshwater fish Danio rerio (zebrafish) and Poecilia reticulata (guppy) change their behavior patterns in terms of avoidance in the presence of a copper gradient? Zebrafish and guppies exposed to a copper gradient were tested for avoidance responses in a free-choice, non-forced, static, multi-compartmented exposure system, using two distinct approaches: (1) monospecific tests, in which only one species was exposed to the copper gradient, at two different population densities; and (2) multispecific tests, in which both species were tested simultaneously. In the control (with no copper) monospecific tests, both species were randomly distributed; however, in the control multispecific test, P. reticulata tended to aggregate. In the monospecific tests with a copper gradient, both species avoided copper in a similar way, with AC 50 (concentration triggering avoidance in 50% of the exposed population) values between 15 and 18 μg·L -1 , irrespective of the population density. However, in the multispecific tests, P. reticulata displaced D. rerio to previously avoided copper levels, consequently increasing the AC 50 of D. rerio to 75 μg·L -1 . This study shows the importance of understanding the interactions among species in contaminated areas, and the way that one species can prevent the avoidance behavior of another. Copyright © 2018 Elsevier B.V. All rights reserved.

MEASURING AND MODELLING METABOLISM

EPA Science Inventory

The use of QSAR with potential metabolism (bioactivation or deactivation) is an experimental approach for exploring toxicity pathways and estimating the relative toxicity of chemicals within a pathway. This conference will hear and discuss the potential and limitations of these ...

Head and Neck Cancer in the Elderly: Frailty, Shared Decisions, and Avoidance of Low Value Care.

PubMed

Mady, Leila J; Nilsen, Marci L; Johnson, Jonas T

2018-05-01

Head and neck cancer (HNC) is a disease of older adults. Recurrent and metastatic head and neck squamous cell carcinoma portends a poor prognosis, with median overall survival of less than 12 months. Within this vulnerable population, significant treatment-related toxicities and physical and psychosocial sequelae can be devastating to quality of life at the end of life. Shared decision making and early comprehensive palliative and support services are at the crux of the approach to older adults with HNC. In doing so, low-value care that fails to meet the goals of patients and their caregivers at the end-of-life may be avoided. Copyright © 2018 Elsevier Inc. All rights reserved.

What Are Nursing Facilities Doing to Reduce Potentially Avoidable Hospitalizations?

PubMed

Daras, Laura Coots; Wang, Joyce M; Ingber, Melvin J; Ormond, Catherine; Breg, Nathaniel W; Khatutsky, Galina; Feng, Zhanlian

2017-05-01

Hospitalizations among nursing facility residents are frequent and often potentially avoidable. A number of initiatives and interventions have been developed to reduce excessive hospitalizations; however, little is known about the specific approaches nursing facilities use to address this issue. The objective of this study is to better understand which types of interventions nursing facilities have introduced to reduce potentially avoidable hospitalizations of long-stay nursing facility residents. Cross-sectional survey. 236 nursing facilities from 7 states. Nursing facility administrators. Web-based survey to measure whether facilities introduced any policies or procedures designed specifically to reduce potentially avoidable hospitalizations of long-stay nursing facility residents between 2011 and 2015. We surveyed facilities about seven types of interventions and quality improvement activities related to reducing avoidable hospitalizations, including use of Interventions to Reduce Acute Care Transfers (INTERACT) and American Medical Directors Association tools. Ninety-five percent of responding nursing facilities reported having introduced at least one new policy or procedure to reduce nursing facility resident hospitalizations since January 2011. The most common practice reported was hospitalization rate tracking or review, followed by standardized communication tools, such as Situation, Background, Assessment, Recommendation (SBAR). We found some variation in the extent and types of these reported interventions. Nearly all facilities surveyed reported having introduced a variety of initiatives to reduce potentially avoidable hospitalizations, likely driven by federal, state, and corporate initiatives to decrease hospital admissions and readmissions. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.

Bioassays for toxicological risk assessment of landfill leachate: A review.

PubMed

Ghosh, Pooja; Thakur, Indu Shekhar; Kaushik, Anubha

2017-07-01

Landfilling is the most common solid waste management practice. However, there exist a potential environmental risk to the surface and ground waters due to the possible leaching of contaminants from the landfill leachates. Current municipal solid waste landfill regulatory approaches consider physicochemical characterization of the leachate and do not assess their potential toxicity. However, assessment of toxic effects of the leachates using rapid, sensitive and cost-effective biological assays is more useful in assessing the risks as they measure the overall toxicity of the chemicals in the leachate. Nevertheless, more research is needed to develop an appropriate matrix of bioassays based on their sensitivity to various toxicants in order to evaluate leachate toxicity. There is a need for a multispecies approach using organisms representing different trophic levels so as to understand the potential impacts of leachate on different trophic organisms. The article reviews different bioassays available for assessing the hazard posed by landfill leachates. From the review it appears that there is a need for a multispecies approach to evaluate leachate toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-01-01

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

Effects of three pesticides on the avoidance behavior of earthworms in laboratory tests performed under temperate and tropical conditions.

PubMed

Garcia, Marcos; Römbke, Jörg; de Brito, Marcus Torres; Scheffczyk, Adam

2008-05-01

Little research has been performed on the impact of pesticides on earthworms under tropical conditions. Taking into consideration the often-limited resources in tropical countries, simple screening tests are needed. Therefore, it was investigated whether three pesticides relevant for the Brazilian Amazon (benomyl, carbendazim, lambda-cyhalothrin) affect the avoidance behavior of the earthworm Eisenia fetida. The tests were performed for two days according to ISO guideline 17512 but were adapted to tropical conditions (i.e. test substrate, test organism and temperature). The results indicate that this test gives reproducible and reliable results. Toxicity values (NOEC, EC50) are lower than those determined in 14 day-acute mortality tests and are approximately in the same range such as those found in 56 day-chronic reproduction tests with the same earthworm species, which were performed in parallel. Therefore, the use of the earthworm avoidance tests is recommended as a screening tool for the risk assessment of pesticides.

Toxic stress and child refugees.

PubMed

Murray, John S

2018-01-01

The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures. The scientists reported that experiencing four or more ACEs during childhood significantly increases the risk for toxic stress. Toxic stress is defined as the exposure to extreme, frequent, and persistent adverse events without the presence of a supportive caretaker. There is a paucity of literature related to toxic stress and child refugees. However, it has been clearly established that the prolonged brutal and traumatizing war in Syria is having a profound impact on the physical and mental health of child refugees at a distressing rate. Prevention of toxic stress should be a primary goal of all pediatric healthcare professionals working with child refugees. While this seems daunting given the population, and the seemingly insurmountable stressors they experience, some basic interventions should be considered. Providing basic anticipatory guidance to parents and caregivers of child refugees, to encourage positive parenting and strengthening support networks, will be highly effective in developing the requisite buffers that mitigate the effects of stress and avoid toxic stress. Efforts should also be focused on addressing caregiver stress and improving their ability to provide safe, reliable, and nurturing care that will help to mitigate any stress response experienced by a child. It is critical that greater awareness be placed on the effects of toxic stress on child refugees who are exposed to significant adverse events early in life. © 2017 Wiley Periodicals, Inc.

Molecular and physiological strategies to increase aluminum resistance in plants.

PubMed

Inostroza-Blancheteau, Claudio; Rengel, Zed; Alberdi, Miren; de la Luz Mora, María; Aquea, Felipe; Arce-Johnson, Patricio; Reyes-Díaz, Marjorie

2012-03-01

Aluminum (Al) toxicity is a primary limitation to plant growth on acid soils. Root meristems are the first site for toxic Al accumulation, and therefore inhibition of root elongation is the most evident physiological manifestation of Al toxicity. Plants may resist Al toxicity by avoidance (Al exclusion) and/or tolerance mechanisms (detoxification of Al inside the cells). The Al exclusion involves the exudation of organic acid anions from the root apices, whereas tolerance mechanisms comprise internal Al detoxification by organic acid anions and enhanced scavenging of free oxygen radicals. One of the most important advances in understanding the molecular events associated with the Al exclusion mechanism was the identification of the ALMT1 gene (Al-activated malate transporter) in Triticum aestivum root cells, which codes for a plasma membrane anion channel that allows efflux of organic acid anions, such as malate, citrate or oxalate. On the other hand, the scavenging of free radicals is dependent on the expression of genes involved in antioxidant defenses, such as peroxidases (e.g. in Arabidopsis thaliana and Nicotiana tabacum), catalases (e.g. in Capsicum annuum), and the gene WMnSOD1 from T. aestivum. However, other recent findings show that reactive oxygen species (ROS) induced stress may be due to acidic (low pH) conditions rather than to Al stress. In this review, we summarize recent findings regarding molecular and physiological mechanisms of Al toxicity and resistance in higher plants. Advances have been made in understanding some of the underlying strategies that plants use to cope with Al toxicity. Furthermore, we discuss the physiological and molecular responses to Al toxicity, including genes involved in Al resistance that have been identified and characterized in several plant species. The better understanding of these strategies and mechanisms is essential for improving plant performance in acidic, Al-toxic soils.

Environmental transmission of generalized anxiety disorder from parents to children: worries, experiential avoidance, and intolerance of uncertainty

PubMed Central

Aktar, Evin; Nikolić, Milica; Bögels, Susan M.

2017-01-01

Generalized anxiety disorder (GAD) runs in families. Building on recent theoretical approaches, this review focuses on potential environmental pathways for parent-to-child transmission of GAD. First, we address child acquisition of a generalized pattern of fearful/anxious and avoidant responding to potential threat from parents via verbal information and via modeling. Next, we address how parenting behaviors may contribute to maintenance of fearful/anxious and avoidant reactions in children. Finally, we consider intergenerational transmission of worries as a way of coping with experiential avoidance of strong negative emotions and with intolerance of uncertainty. We conclude that parents with GAD may bias their children's processing of potential threats in the environment by conveying the message that the world is not safe, that uncertainty is intolerable, that strong emotions should be avoided, and that worry helps to cope with uncertainty, thereby transmitting cognitive styles that characterize GAD. Our review highlights the need for research on specific pathways for parent-to-child transmission of GAD. PMID:28867938

Environmental transmission of generalized anxiety disorder from parents to children: worries, experiential avoidance, and intolerance of uncertainty.

PubMed

Aktar, Evin; Nikolić, Milica; Bögels, Susan M

2017-06-01

Generalized anxiety disorder (GAD) runs in families. Building on recent theoretical approaches, this review focuses on potential environmental pathways for parent-to-child transmission of GAD. First, we address child acquisition of a generalized pattern of fearful/anxious and avoidant responding to potential threat from parents via verbal information and via modeling. Next, we address how parenting behaviors may contribute to maintenance of fearful/anxious and avoidant reactions in children. Finally, we consider intergenerational transmission of worries as a way of coping with experiential avoidance of strong negative emotions and with intolerance of uncertainty. We conclude that parents with GAD may bias their children's processing of potential threats in the environment by conveying the message that the world is not safe, that uncertainty is intolerable, that strong emotions should be avoided, and that worry helps to cope with uncertainty, thereby transmitting cognitive styles that characterize GAD. Our review highlights the need for research on specific pathways for parent-to-child transmission of GAD.

TOXICITY TESTING IN THE 21ST CENTURY: A VISION AND A STRATEGY

PubMed Central

Krewski, Daniel; Acosta, Daniel; Andersen, Melvin; Anderson, Henry; Bailar, John C.; Boekelheide, Kim; Brent, Robert; Charnley, Gail; Cheung, Vivian G.; Green, Sidney; Kelsey, Karl T.; Kerkvliet, Nancy I.; Li, Abby A.; McCray, Lawrence; Meyer, Otto; Patterson, Reid D.; Pennie, William; Scala, Robert A.; Solomon, Gina M.; Stephens, Martin; Yager, James; Zeise, Lauren

2015-01-01

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology. PMID:20574894

Application of the Activity Framework for Assessing Aquatic Ecotoxicology Data for Organic Chemicals.

PubMed

Thomas, Paul; Dawick, James; Lampi, Mark; Lemaire, Philippe; Presow, Shaun; van Egmond, Roger; Arnot, Jon A; Mackay, Donald; Mayer, Philipp; Galay Burgos, Malyka

2015-10-20

Toxicological research in the 1930s gave the first indications of the link between narcotic toxicity and the chemical activity of organic chemicals. More recently, chemical activity has been proposed as a novel exposure parameter that describes the fraction of saturation and that quantifies the potential for partitioning and diffusive uptake. In the present study, more than 2000 acute and chronic algal, aquatic invertebrates and fish toxicity data, as well as water solubility and melting point values, were collected from a series of sources. The data were critically reviewed and grouped by mode of action (MoA). We considered 660 toxicity data to be of acceptable quality. The 328 data which applied to the 72 substances identified as MoA 1 were then evaluated within the activity-toxicity framework: EC50 and LC50 values for all three taxa correlated generally well with (subcooled) liquid solubilities. Acute toxicity was typically exerted within the chemical activity range of 0.01-0.1, whereas chronic toxicity was exerted in the range of 0.001-0.01. These results confirm that chemical activity has the potential to contribute to the determination, interpretation and prediction of toxicity to aquatic organisms. It also has the potential to enhance regulation of organic chemicals by linking results from laboratory tests, monitoring and modeling programs. The framework can provide an additional line of evidence for assessing aquatic toxicity, for improving the design of toxicity tests, reducing animal usage and addressing chemical mixtures.

A novel in-situ-gelling liquid suppository for site-targeting delivery of anti-colorectal cancer drugs.

PubMed

Lin, Hong-Ru; Tseng, Chao-Chih; Lin, Yiu-Jiuan; Ling, Ming-Hung

2012-01-01

In order to avoid anti-cancer drugs undergoing a first-pass effect and reduce their toxicity, and to solve conventional suppositories defects, we developed an in-situ-gelling and injectable Pluronic-poly(acrylic acid) (Pluronic-PAA) liquid suppository, which could gel fast in the physiological state and had suitable gel strength and bioadhesive force. The liquid suppositories were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum for at least 6 h and while releasing the drug. The toxicity and cytotoxic tests indicated that Pluronic and PAA were non-toxic materials and could inhibit colon cancer cells when oxaliplatin was incorporated. C max and AUC0→12h values of oxaliplatin after rectal administration of a oxaliplatin suppository were higher than those for an oxaliplatin solution administered orally. These results suggest that an in-situ-gelling and injectable liquid suppository for humans can be further developed as a more convenient and effective rectal dosage form.

Stinging wasps (Hymenoptera: Aculeata), which species have the longest sting?

PubMed

Sadler, Emily A; Pitts, James P; Wilson, Joseph S

2018-01-01

The stings of bees, wasps, and ants are something that catches the attention of anyone that experiences them. While many recent studies have focused on the pain inflicted by the stings of various stinging wasps, bees, or ants (Hymenoptera: Aculeata), little is known about how the length of the sting itself varies between species. Here, we investigate the sting length of a variety of aculeate wasps, and compare that to reported pain and toxicity values. We find that velvet ants (Hymenoptera: Mutillidae) have the longest sting compared to their body size out of any bee, wasp, or ant species. We also find that there is no link between relative sting length and pain; however, we did find an inverse relationship between relative sting length and toxicity with taxa having shorter relative stings being more toxic. While we found a significant relationship between host use and relative sting length, we suggest that the long sting length of the velvet ants is also related to their suite of defenses to avoid predation.

Proteome Profiling of BEAS-2B Cells Treated with Titanium Dioxide Reveals Potential Toxicity of and Detoxification Pathways for Nanomaterial

EPA Science Inventory

Oxidative stress is known to play important roles in nanomaterial-induced toxicities. However, the proteins and signaling pathways associated with nanomaterial-mediated oxidative stress and toxicity are largely unknown. To identify oxidative stress-responding toxicity pathways an...

Proteome Profiling Reveals Potential Toxicity and Detoxification Pathways Following Exposure of BEAS-2B Cells to Engineered Titanium Dioxide Nanoparticles

EPA Science Inventory

Oxidative stress is known to play important roles in engineered nanomaterial induced cellular toxicity. However, the proteins and signaling pathways associated with the engineered nanomaterial mediated oxidative stress and toxicity are largely unknown. To identify these toxicity ...

EPA’s ToxCast Program for Predicting Toxicity and Prioritizing Chemicals for Further Screening and Testing

EPA Science Inventory

Testing of environmental and industrial chemicals for toxicity potential is a daunting task because of the wide range of possible toxicity mechanisms. Although animal testing is one means of achieving broad toxicity coverage, evaluation of large numbers of chemicals is challengin...

USING THE MEDAKA EMBRYO ASSAY TO INVESTIGATE DEVELOPMENTAL ETHANOL TOXICITY.

EPA Science Inventory

Ethanol (EtOH) is a well-known developmental toxicant that produces a range of abnormal phenotypes. While the toxic potential of developmental EtOH exposure is well characterized, the effect of the timing of exposure on the extent of toxicity remains unknown. Fish models such as ...

40 CFR 798.4900 - Developmental toxicity study.

Code of Federal Regulations, 2011 CFR

2011-07-01

... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

40 CFR 798.4900 - Developmental toxicity study.

Code of Federal Regulations, 2012 CFR

2012-07-01

... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 33 2012-07-01 2012-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

40 CFR 798.4900 - Developmental toxicity study.

Code of Federal Regulations, 2013 CFR

2013-07-01

... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

40 CFR 798.4900 - Developmental toxicity study.

Code of Federal Regulations, 2014 CFR

2014-07-01

... study is designed to provide information on the potential hazard to the unborn which may arise from... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Developmental toxicity study. 798.4900... Developmental toxicity study. (a) Purpose. In the assessment and evaluation of the toxic characteristics of a...

Biotic and abiotic studies on the biological fate, transport and ecotoxicity of toxic and hazardous waste in the Mississippi River basin

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

Abdelghani, A.; Pramar, Y.; Mandal, T.

1996-05-02

This project assesses the levels of xenobiotics in Devils Swamp and studies their biological fate, transport, ecotoxicity, and potential toxicity to man. This article reports on the following studies: assessment of the acute toxicity of individual xenobiotics and toxicity of organic compounds hexachlorobutadience (HCB) and hexachlorobenzene (HCBD) on juvenile crayfish; determination of the biotic influence of temperature, salinity, pH, oxidation-reduction potential, and sediment composition on the migration of xenobiotics; development of a pharmacokinetics model for xenobiotic absorption and storage, distribution and excretion by fish and crayfish.

Human health risk from heavy metal via food crops consumption with wastewater irrigation practices in Pakistan.

PubMed

Khan, Muhammad Usman; Malik, Riffat Naseem; Muhammad, Said

2013-11-01

The current study was designed to investigate the potential human health risks associated with consumption of food crops contaminated with toxic heavy metals. Cadmium (Cd) concentration in surface soils; Cd, lead (Pb) and chromium (Cr) in the irrigation water and food crops were above permissible limits. The accumulation factor (AF) was >1 for manganese (Mn) and Pb in different food crops. The Health Risk Index (HRI) was >1 for Pb in all food crops irrigated with wastewater and tube well water. HRI >1 was also recorded for Cd in all selected vegetables; and for Mn in Spinacia oleracea irrigated with wastewater. All wastewater irrigated samples (soil and food crops) exhibited high relative contamination level as compared to samples irrigated with tube well water. Our results emphasized the need for pretreatment of wastewater and routine monitoring in order to avoid contamination of food crops from the wastewater irrigation system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Production of microbial biosurfactants by solid-state cultivation.

PubMed

Krieger, Nadia; Camilios Neto, Doumit; Mitchell, David Alexander

2010-01-01

In recent years biosurfactants have attracted attention because of their low toxicity, biodegradability and ecological acceptability. However, their use is currently extremely limited due to their high cost in relation to that of chemical surfactants. Solid-state cultivation represents an alternative technology for biosurfactant production that can bring two important advantages: firstly, it allows the use of inexpensive substrates and, secondly, it avoids the problem of foaming that complicates submerged cultivation processes for biosurfactant production. In this chapter we show that, despite its potential, to date relatively little attention has been given to solid-state cultivation for biosurfactant production. We also note that this cultivation technique brings its own challenges, such as the selection of a bioreactor type that will allow adequate heat removal, of substrates with appropriate physico-chemical properties and of methods for monitoring of the cultivation process and recovering the biosurfactants from the fermented solid. With suitable efforts in research, solid-state cultivation can be used for large-scale production of biosurfactants.

Nectar Attracts Foraging Honey Bees with Components of Their Queen Pheromones.

PubMed

Liu, Fanglin; Gao, Jie; Di, Nayan; Adler, Lynn S

2015-11-01

Floral nectar often contains chemicals that are deterrent to pollinators, presenting potential challenges to outcrossing plant species. Plants may be able to co-opt pollinator chemical signals to mitigate the negative effects of nectar deterrent compounds on pollination services. We found that buckwheat (Fagopyrum esculentum) and Mexican sunflower (Tithonia diversifolia) produce nectar with abundant phenolics, including three components of the Apis honeybee queen mandibular pheromone (QMP). In addition, these nectars contain a non-pheromonal phenolic, chlorogenic acid (CA), which was toxic to honeybees, and T. diversifolia nectar also contained isochlorogenic acid (IA). Fresh nectar or solutions containing nectar phenolics reduced Apis individual feeding compared to sucrose solutions. However, freely foraging bees preferred solutions with QMP components to control solutions, and QMP components over-rode or reversed avoidance of CA and IA. Furthermore, prior exposure to the presence or just the odor of QMP components removed the deterrent effects of CA and IA. By mimicking the honey bee pheromone blend, nectar may maintain pollinator attraction in spite of deterrent nectar compounds.

A Comparative Approach for Ranking Contaminated Sites Based on the Risk Assessment Paradigm Using Fuzzy PROMETHEE

NASA Astrophysics Data System (ADS)

Zhang, Kejiang; Kluck, Cheryl; Achari, Gopal

2009-11-01

A ranking system for contaminated sites based on comparative risk methodology using fuzzy Preference Ranking Organization METHod for Enrichment Evaluation (PROMETHEE) was developed in this article. It combines the concepts of fuzzy sets to represent uncertain site information with the PROMETHEE, a subgroup of Multi-Criteria Decision Making (MCDM) methods. Criteria are identified based on a combination of the attributes (toxicity, exposure, and receptors) associated with the potential human health and ecological risks posed by contaminated sites, chemical properties, site geology and hydrogeology and contaminant transport phenomena. Original site data are directly used avoiding the subjective assignment of scores to site attributes. When the input data are numeric and crisp the PROMETHEE method can be used. The Fuzzy PROMETHEE method is preferred when substantial uncertainties and subjectivities exist in site information. The PROMETHEE and fuzzy PROMETHEE methods are both used in this research to compare the sites. The case study shows that this methodology provides reasonable results.

New CVD-based method for the growth of high-quality crystalline zinc oxide layers

NASA Astrophysics Data System (ADS)

Huber, Florian; Madel, Manfred; Reiser, Anton; Bauer, Sebastian; Thonke, Klaus

2016-07-01

High-quality zinc oxide (ZnO) layers were grown using a new chemical vapour deposition (CVD)-based low-cost growth method. The process is characterized by total simplicity, high growth rates, and cheap, less hazardous precursors. To produce elementary zinc vapour, methane (CH4) is used to reduce a ZnO powder. By re-oxidizing the zinc with pure oxygen, highly crystalline ZnO layers were grown on gallium nitride (GaN) layers and on sapphire substrates with an aluminum nitride (AlN) nucleation layer. Using simple CH4 as precursor has the big advantage of good controllability and the avoidance of highly toxic gases like nitrogen oxides. In photoluminescence (PL) measurements the samples show a strong near-band-edge emission and a sharp line width at 5 K. The good crystal quality has been confirmed in high resolution X-ray diffraction (HRXRD) measurements. This new growth method has great potential for industrial large-scale production of high-quality single crystal ZnO layers.

A brief review on the application of nanoparticle enclosed herbal medicine for the treatment of infective endocarditis.

PubMed

Namdari, Mehrdad; Eatemadi, Ali; Soleimaninejad, Maryam; Hammed, Aiyelabegan T

2017-03-01

Herbal medicines have been routinely employed all over the world dated back from the ancient time and have been identified by patients and physicians for their excellent therapeutic value as they have lower adverse effects when compared with the modern medicines. Phytotherapeutics requires a scientific technique to deliver the active herbal extract in a controlled manner to avoid repeated administration and increase patient compliance. This can be reached by fabricating a novel drug delivery systems (NDDS) for herbal components. NDDSs does not only decrease the repeated dose to overcome ineffectiveness, but also help to increase potency by decreasing toxicity and elevating drug bioavailability. Nano-sized DDS of herbal drugs have a potential application for improving the activity and countering the problems related to herbal medicines. Hence, application of nanocarriers as an NDDS in the traditional herbal medicine system is important to treat more chronic diseases like infectious endocarditis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent.

PubMed

Lewis, Susan J; Mueller, Bruce A

2014-01-01

Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT. We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients. © 2014 Wiley Periodicals, Inc.

Combined exposure to low doses of pesticides causes decreased birth weights in rats.

PubMed

Hass, Ulla; Christiansen, Sofie; Axelstad, Marta; Scholze, Martin; Boberg, Julie

2017-09-01

Decreased birth weight is a common effect of many pesticides in reproductive toxicity studies, but there are no empirical data on how pesticides act in combination on this endpoint. We hypothesized that a mixture of six pesticides (cyromazine, MCPB, pirimicarb, quinoclamine, thiram, and ziram) would decrease birth weight, and that these mixture effects could be predicted by the Dose Addition model. Data for the predictions were obtained from the Draft Assessment Reports of the individual pesticides. A mixture of equi-effective doses of these pesticides was tested in two studies in Wistar rats, showing mixture effects in good agreement with the additivity predictions. Significantly lower birth weights were observed when compounds were present at individual doses below their no-observed adverse effect levels (NOAELs). These results emphasize the need for cumulative risk assessment of pesticides to avoid potentially serious impact of mixed exposure on prenatal development and pregnancy in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

General Method to Determine the Flux of Charged Molecules through Nanopores Applied to β-Lactamase Inhibitors and OmpF.

PubMed

Ghai, Ishan; Pira, Alessandro; Scorciapino, Mariano Andrea; Bodrenko, Igor; Benier, Lorraine; Ceccarelli, Matteo; Winterhalter, Mathias; Wagner, Richard

2017-03-16

A major challenge in the discovery of the new antibiotics against Gram-negative bacteria is to achieve sufficiently fast permeation in order to avoid high doses causing toxic side effects. So far, suitable assays for quantifying the uptake of charged antibiotics into bacteria are lacking. We apply an electrophysiological zero-current assay using concentration gradients of β-lactamase inhibitors combined with single-channel conductance to quantify their flux rates through OmpF. Molecular dynamic simulations provide in addition details on the interactions between the nanopore wall and the charged solutes. In particular, the interaction barrier for three β-lactamase inhibitors is surprisingly as low as 3-5 kcal/mol and only slightly above the diffusion barrier of ions such as chloride. Within our macroscopic constant field model, we determine that at a zero-membrane potential a concentration gradient of 10 μM of avibactam, sulbactam, or tazobactam can create flux rates of roughly 620 molecules/s per OmpF trimer.

Uranium induces oxidative stress in lung epithelial cells

PubMed Central

Periyakaruppan, Adaikkappan; Kumar, Felix; Sarkar, Shubhashish; Sharma, Chidananda S.

2009-01-01

Uranium compounds are widely used in the nuclear fuel cycle, antitank weapons, tank armor, and also as a pigment to color ceramics and glass. Effective management of waste uranium compounds is necessary to prevent exposure to avoid adverse health effects on the population. Health risks associated with uranium exposure includes kidney disease and respiratory disorders. In addition, several published results have shown uranium or depleted uranium causes DNA damage, mutagenicity, cancer and neurological defects. In the current study, uranium toxicity was evaluated in rat lung epithelial cells. The study shows uranium induces significant oxidative stress in rat lung epithelial cells followed by concomitant decrease in the antioxidant potential of the cells. Treatment with uranium to rat lung epithelial cells also decreased cell proliferation after 72 h in culture. The decrease in cell proliferation was attributed to loss of total glutathione and superoxide dismutase in the presence of uranium. Thus the results indicate the ineffectiveness of antioxidant system’s response to the oxidative stress induced by uranium in the cells. PMID:17124605

Chemical inhibition of prometastatic lysyl-tRNA synthetase–laminin receptor interaction

PubMed Central

Kim, Dae Gyu; Lee, Jin Young; Kwon, Nam Hoon; Fang, Pengfei; Zhang, Qian; Wang, Jing; Young, Nicolas L.; Guo, Min; Cho, Hye Young; Mushtaq, AmeeqUl; Jeon, Young Ho; Choi, Jin Woo; Han, Jung Min; Kang, Ho Woong; Joo, Jae Eun; Hur, Youn; Kang, Wonyoung; Yang, Heekyoung; Nam, Do-Hyun; Lee, Mi-Sook; Lee, Jung Weon; Kim, Eun-Sook; Moon, Aree; Kim, Kibom; Kim, Doyeun; Kang, Eun Joo; Moon, Youngji; Rhee, Kyung Hee; Han, Byung Woo; Yang, Jee Sun; Han, Gyoonhee; Yang, Won Suk; Lee, Cheolju; Wang, Ming-Wei; Kim, Sunghoon

2014-01-01

Lysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds to KRS, impinged on interaction of KRS with 67LR and suppressed metastasis in 3 different mouse models. The compound inhibited KRS–67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS–67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS. PMID:24212136

What is the role of metabolic hormones in taste buds of the tongue.

PubMed

Cai, Huan; Maudsley, Stuart; Martin, Bronwen

2014-01-01

Gustation is one of the important chemical senses that guides the organism to identify nutrition while avoiding toxic chemicals. An increasing number of metabolic hormones and/or hormone receptors have been identified in the taste buds of the tongue and are involved in modulating taste perception. The gustatory system constitutes an additional endocrine regulatory locus that affects food intake, and in turn whole-body energy homeostasis. Here we provide an overview of the main metabolic hormones known to be present in the taste buds of the tongue; discuss their potential functional roles in taste perception and energy homeostasis and how their functional integrity is altered in the metabolic imbalance status (obesity and diabetes) and aging process. Better understanding of the functional roles of metabolic hormones in flavor perception as well as the link between taste perception and peripheral metabolism may be vital for developing strategies to promote healthier eating and prevent obesity or lifestyle-related disorders. © 2014 S. Karger AG, Basel.

Evaluation of actinide biosorption by microorganisms

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

Happel, A.M.

1996-06-01

Conventional methods for removing metals from aqueous solutions include chemical precipitation, chemical oxidation or reduction, ion exchange, reverse osmosis, electrochemical treatment and evaporation. The removal of radionuclides from aqueous waste streams has largely relied on ion exchange methods which can be prohibitively costly given increasingly stringent regulatory effluent limits. The use of microbial cells as biosorbants for heavy metals offers a potential alternative to existing methods for decontamination or recovery of heavy metals from a variety of industrial waste streams and contaminated ground waters. The toxicity and the extreme and variable conditions present in many radionuclide containing waste streams maymore » preclude the use of living microorganisms and favor the use of non-living biomass for the removal of actinides from these waste streams. In the work presented here, we have examined the biosorption of uranium by non-living, non-metabolizing microbial biomass thus avoiding the problems associated with living systems. We are investigating biosorption with the long term goal of developing microbial technologies for the remediation of actinides.« less

Bioengineered protein-based nanocage for drug delivery.

PubMed

Lee, Eun Jung; Lee, Na Kyeong; Kim, In-San

2016-11-15

Nature, in its wonders, presents and assembles the most intricate and delicate protein structures and this remarkable phenomenon occurs in all kingdom and phyla of life. Of these proteins, cage-like multimeric proteins provide spatial control to biological processes and also compartmentalizes compounds that may be toxic or unstable and avoids their contact with the environment. Protein-based nanocages are of particular interest because of their potential applicability as drug delivery carriers and their perfect and complex symmetry and ideal physical properties, which have stimulated researchers to engineer, modify or mimic these qualities. This article reviews various existing types of protein-based nanocages that are used for therapeutic purposes, and outlines their drug-loading mechanisms and bioengineering strategies via genetic and chemical functionalization. Through a critical evaluation of recent advances in protein nanocage-based drug delivery in vitro and in vivo, an outlook for de novo and in silico nanocage design, and also protein-based nanocage preclinical and future clinical applications will be presented. Copyright © 2016 Elsevier B.V. All rights reserved.

The Scarlet Letter of Alkylation: A Mini Review of Selective Alkylating Agents

PubMed Central

Oronsky, Bryan T; Reid, Tony; Knox, Susan J; Scicinski, Jan J

2012-01-01

If there were a stigma scale for chemotherapy, alkylating agents would be ranked at the top of the list. The chemical term alkylation is associated with nonselective toxicity, an association that dates back to the use of nitrogen mustards during World War I as chemical warfare agents. That this stigma persists and extends to compounds that, through selectivity, attempt to “tame” the indiscriminate destructive potential of alkylation is the subject of this review. Selective alkylation, as it is referred to herein, constitutes an extremely nascent and dynamic field in oncology. The pharmacodynamic response to this selective strategy depends on a delicate kinetic balance between specificity and the rate and extent of binding. Three representative compounds are presented: RRx-001, 3-bromopyruvate, and TH-302. The main impetus for the development of these compounds has been the avoidance of the serious complications of traditional alkylating agents; therefore, it is the thesis of this review that they should not experience stigma by association. PMID:22937173

Passage of irinotecan and its active metabolite, SN-38, into human milk.

PubMed

Nakagawa, J; Terui, K; Hosoi, K; Ueno, K; Yokoyama, Y; Hayakari, M

2016-10-01

We measured the levels of irinotecan and its active metabolite, SN-38, in human milk after the administration of irinotecan to assess the potential risks when women treated with irinotecan nurse their infants. Human milk was collected for 6 days starting on the day after irinotecan was administered. The levels of irinotecan and SN-38 in human milk were measured using liquid chromatography-mass spectrometry. Irinotecan was detected on Days 2 and 3 but not after Day 4. A strong signal indicating the presence of SN-38 was detected on Day 2 and the signal was readily detected until Day 7, indicating that SN-38 remained in human milk. Intravenously administered CPT-11 continues to pass into human milk over a prolonged period in the form of its active metabolite, SN-38. The relationship between administration of CPT-11 and SN-38 exposure and toxicity is still not well defined, so patients should avoid nursing their infants while they are being treated with CPT-11. © 2016 John Wiley & Sons Ltd.

Supercritical fluid extraction of plant flavors and fragrances.

PubMed

Capuzzo, Andrea; Maffei, Massimo E; Occhipinti, Andrea

2013-06-19

Supercritical fluid extraction (SFE) of plant material with solvents like CO₂, propane, butane, or ethylene is a topic of growing interest. SFE allows the processing of plant material at low temperatures, hence limiting thermal degradation, and avoids the use of toxic solvents. Although today SFE is mainly used for decaffeination of coffee and tea as well as production of hop extracts on a large scale, there is also a growing interest in this extraction method for other industrial applications operating at different scales. In this review we update the literature data on SFE technology, with particular reference to flavors and fragrance, by comparing traditional extraction techniques of some industrial medicinal and aromatic crops with SFE. Moreover, we describe the biological activity of SFE extracts by describing their insecticidal, acaricidal, antimycotic, antimicrobial, cytotoxic and antioxidant properties. Finally, we discuss the process modelling, mass-transfer mechanisms, kinetics parameters and thermodynamic by giving an overview of SFE potential in the flavors and fragrances arena.

Therapeutic Antisense Oligonucleotides against Cancer: Hurdling to the Clinic

NASA Astrophysics Data System (ADS)

Moreno, Pedro; Pêgo, Ana

2014-10-01

Under clinical development since the early 90’s and with two successfully approved drugs (Fomivirsen and Mipomersen), oligonucleotide-based therapeutics have not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given towards a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field.

Therapeutic antisense oligonucleotides against cancer: hurdling to the clinic

PubMed Central

Moreno, Pedro M. D.; Pêgo, Ana P.

2014-01-01

Under clinical development since the early 90's and with two successfully approved drugs (Fomivirsen and Mipomersen), oligonucleotide-based therapeutics has not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given toward a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field. PMID:25353019

Tobacco and areca nut chewing--reproductive impairments: an overview.

PubMed

Kumar, Sunil

2013-04-01

A large number of people are using smokeless tobacco and areca nut worldwide. Sufficient data on tobacco smoking have harmful effect on human health and reproduction is available. However, data on the smokeless tobacco and areca nut use on human reproduction is scanty. This overview is an attempt to compose on the consumption of smokeless tobacco and areca nut on human reproduction and some relevant experimental data were also included. The existing studies suggest that tobacco and areca nut chewing alone, together or with other ingredients had reproductive toxic potential. Pregnant women using smokeless tobacco during pregnancy also had adverse effect on pregnancy and its outcome. Thus pregnant women must avoid consumption of any mixture containing areca nut and tobacco in order to protect the pregnancy and outcome. The data suggest that smokeless tobacco use is also harmful as smoking for reproduction and use of areca nut might have further compounded the problem. Copyright © 2012 Elsevier Inc. All rights reserved.

A comparative approach for ranking contaminated sites based on the risk assessment paradigm using fuzzy PROMETHEE.

PubMed

Zhang, Kejiang; Kluck, Cheryl; Achari, Gopal

2009-11-01

A ranking system for contaminated sites based on comparative risk methodology using fuzzy Preference Ranking Organization METHod for Enrichment Evaluation (PROMETHEE) was developed in this article. It combines the concepts of fuzzy sets to represent uncertain site information with the PROMETHEE, a subgroup of Multi-Criteria Decision Making (MCDM) methods. Criteria are identified based on a combination of the attributes (toxicity, exposure, and receptors) associated with the potential human health and ecological risks posed by contaminated sites, chemical properties, site geology and hydrogeology and contaminant transport phenomena. Original site data are directly used avoiding the subjective assignment of scores to site attributes. When the input data are numeric and crisp the PROMETHEE method can be used. The Fuzzy PROMETHEE method is preferred when substantial uncertainties and subjectivities exist in site information. The PROMETHEE and fuzzy PROMETHEE methods are both used in this research to compare the sites. The case study shows that this methodology provides reasonable results.

Population properties affect inbreeding avoidance in moose

PubMed Central

Herfindal, Ivar; Haanes, Hallvard; Røed, Knut H.; Solberg, Erling J.; Markussen, Stine S.; Heim, Morten; Sæther, Bernt-Erik

2014-01-01

Mechanisms reducing inbreeding are thought to have evolved owing to fitness costs of breeding with close relatives. In small and isolated populations, or populations with skewed age- or sex distributions, mate choice becomes limited, and inbreeding avoidance mechanisms ineffective. We used a unique individual-based dataset on moose from a small island in Norway to assess whether inbreeding avoidance was related to population structure and size, expecting inbreeding avoidance to be greater in years with larger populations and even adult sex ratios. The probability that a potential mating event was realized was negatively related to the inbreeding coefficient of the potential offspring, with a stronger relationship in years with a higher proportion or number of males in the population. Thus, adult sex ratio and population size affect the degree of inbreeding avoidance. Consequently, conservation managers should aim for sex ratios that facilitate inbreeding avoidance, especially in small and isolated populations. PMID:25540152

Toxicity assessment for petroleum-contaminated soil using terrestrial invertebrates and plant bioassays.

PubMed

Hentati, Olfa; Lachhab, Radhia; Ayadi, Mariem; Ksibi, Mohamed

2013-04-01

The assessment of soil quality after a chemical or oil spill and/or remediation effort may be measured by evaluating the toxicity of soil organisms. To enhance our understanding of the soil quality resulting from laboratory and oil field spill remediation, we assessed toxicity levels by using earthworms and springtails testing and plant growth experiments. Total petroleum hydrocarbons (TPH)-contaminated soil samples were collected from an oilfield in Sfax, Tunisia. Two types of bioassays were performed. The first assessed the toxicity of spiked crude oil (API gravity 32) in Organization for Economic Co-operation and Development artificial soil. The second evaluated the habitat function through the avoidance responses of earthworms and springtails and the ability of Avena sativa to grow in TPH-contaminated soils diluted with farmland soil. The EC50 of petroleum-contaminated soil for earthworms was 644 mg of TPH/kg of soil at 14 days, with 67 % of the earthworms dying after 14 days when the TPH content reached 1,000 mg/kg. The average germination rate, calculated 8 days after sowing, varied between 64 and 74 % in low contaminated soils and less than 50 % in highly contaminated soils.

Stabilizing the baseline current of a microbial fuel cell-based biosensor through overpotential control under non-toxic conditions.

PubMed

Stein, Nienke E; Hamelers, Hubertus V M; Buisman, Cees N J

2010-04-01

A MFC-based biosensor can act as online toxicity sensor. Electrical current is a direct linear measure for metabolic activity of electrochemically active microorganisms. Microorganisms gain energy from anodic overpotential and current strongly depends on anodic overpotential. Therefore control of anodic overpotential is necessary to detect toxic events and prevent false positive alarms. Anodic overpotential and thus current is influenced by anode potential, pH, substrate and bicarbonate concentrations. In terms of overpotential all factor showed a comparable effect, anode potential 1.2% change in current density per mV, pH 0.43%/mV, bicarbonate 0.75%/mV and acetate 0.8%/mV. At acetate saturation the maximum acetate conversion rate is reached and with that a constant bicarbonate concentration. Control of acetate and bicarbonate concentration can be less strict than control of anode potential and pH. Current density changes due to changing anode potential and pH are in the same order of magnitude as changes due to toxicity. Strict control of pH and anode potential in a small range is required. The importance of anodic overpotential control for detection of toxic compounds is shown. To reach a stable baseline current under nontoxic conditions a MFC-based biosensor should be operated at controlled anode potential, controlled pH and saturated substrate concentrations. 2009 Elsevier B.V. All rights reserved.

RIFM fragrance ingredient safety assessment, isobornyl isovalerate, CAS registry number 7779-73-9.

PubMed

Api, A M; Belsito, D; Bhatia, S; Bruze, M; Calow, P; Dagli, M L; Dekant, W; Fryer, A D; Kromidas, L; La Cava, S; Lapczynski, A; Liebler, D C; O'Brien, D; Parakhia, R; Penning, T M; Politano, V T; Ritacco, G; Salvito, D; Schultz, T W; Shen, J; Sipes, I G; Wall, B; Wilcox, D K

2017-12-01

This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization potential, as well as, environmental safety. Data from the suitable read across analog isobornyl acetate (CAS # 125-12-2) show that this material is not genotoxic, provided a MOE > 100 for the repeated dose, developmental and reproductive endpoints, and does not have skin sensitization potential. The local respiratory toxicity endpoint was completed using the TTC (threshold of Toxicological Concern) for a Cramer Class II material (0.47 mg/day). The phototoxicity/photoallergenicity endpoint was completed based on suitable UV spectra. The environmental endpoint was completed as described in the RIFM Framework. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing the Potential Environmental Consequences of a New Energetic Material: A Phased Approach, September 2005

DTIC Science & Technology

2007-12-01

there are no reliable alternatives to animal testing in the determination of toxicity. QSARs are only as reliable as the corroborating toxicological ...2) QSAR approaches can also be used to estimate toxicological impact. Toxicity QSAR models can often predict many toxicity parameters without... Toxicology Study No. 87-XE-03N3-05, Assessing the Potential Environmental Consequences of a New Energetic Material: A Phased Approach, September 2005 1

Maternally Mediated Developmental Toxicity

EPA Science Inventory

The current practice for the assessment of an agent’s potential effects on the developing embryo/fetus includes administration of high, maternally toxic doses to pregnant laboratory animals. For most agents evaluated, developmental effects occur concomitant with maternal toxicity...

The Freon loop double containment design for Spacelab refrigerator/freezer to protect environment

NASA Technical Reports Server (NTRS)

Hye, A.

1985-01-01

General Electric is building a vapor compression refrigerator/freezer for NASA-Johnson Space Center for the Spacelab mission SLS-1 for life sciences experiments. Freon R502 is used as refrigerant. As R502 is considered toxic, the whole Freon loop is enclosed in a second containment to avoid exposure to crewmen. A detailed description of the design and construction of the safety enclosure is presented.

Biofiltration as a Viable Alternative for Air Pollution Control at Department of Defense Surface Coating Facilities

DTIC Science & Technology

2007-03-01

enzymes or energy to break down the contaminants (Devinny, 1999). Known biologically toxic compounds should be avoided altogether if using a...mesophilic and thermophilic temperature ranges, however, most biodegradation is executed by mesophiles and thermophiles (Leson and Winer, 1991). Of...ambient temperatures. Some microbes are known to function effectively in thermophilic conditions (40-55 °C). For example, microbes were shown to have

Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers.

PubMed

Efferth, Thomas; Volm, Manfred

2017-07-01

The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR). Hence ABC-transporters may have opposing effects for organismic health reaching from harmful in MDR of tumors to beneficial for maintenance of health in MXR. While their inhibition by specific inhibitors may improve treatment success in oncology and avoid carcinogenesis, blocking of ABC-transporter-driven efflux by environmental pollutants leads to ecotoxicological consequences in marine biotopes. Poisoned seafood may enter the food-chain and cause intoxications in human beings. As exemplified with ABC-transporters, joining forces in interdisciplinary research may, therefore, be a wise strategy to fight problems in human medicine and environmental sciences.

Neuroprotective effects of the polyphenolic antioxidant agent, Curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat.

PubMed

Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Kazeminejad, Behrang

2010-10-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of these diseases. In this study, the possible antioxidant and neuroprotective properties of the polyphenolic antioxidant compound, Curcumin against homocysteine (Hcy) neurotoxicity was investigated. Curcumin (5 and 50mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intrahippocampal injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24h after the last Curcumin or its vehicle injection. We detected Malondialdehyde (MDA) and Super oxide anion (SOA) in rats' hippocampi. Results indicated that Hcy could induce lipid peroxidation and increase MDA and SOA levels in rats' hippocampi. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, Curcumin treatment decreased MDA and SOA levels significantly as well as improved learning and memory in rats. Histopathological analysis also indicated that Hcy could decrease hippocampus cell count and Curcumin inhibited this toxic effect. These results suggest that Hcy may induce lipid peroxidation in rats' hippocampi and polyphenol treatment (Curcumin) improved learning and memory deficits by protecting the nervous system against Hcy toxicity. (c) 2010 Elsevier Inc. All rights reserved.

An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

PubMed Central

Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

2017-01-01

Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

A systematic evaluation of chemicals in hydraulic-fracturing fluids and wastewater for reproductive and developmental toxicity.

PubMed

Elliott, Elise G; Ettinger, Adrienne S; Leaderer, Brian P; Bracken, Michael B; Deziel, Nicole C

2017-01-01

Hydraulic-fracturing fluids and wastewater from unconventional oil and natural gas development contain hundreds of substances with the potential to contaminate drinking water. Challenges to conducting well-designed human exposure and health studies include limited information about likely etiologic agents. We systematically evaluated 1021 chemicals identified in hydraulic-fracturing fluids (n=925), wastewater (n=132), or both (n=36) for potential reproductive and developmental toxicity to triage those with potential for human health impact. We searched the REPROTOX database using Chemical Abstract Service registry numbers for chemicals with available data and evaluated the evidence for adverse reproductive and developmental effects. Next, we determined which chemicals linked to reproductive or developmental toxicity had water quality standards or guidelines. Toxicity information was lacking for 781 (76%) chemicals. Of the remaining 240 substances, evidence suggested reproductive toxicity for 103 (43%), developmental toxicity for 95 (40%), and both for 41 (17%). Of these 157 chemicals, 67 had or were proposed for a federal water quality standard or guideline. Our systematic screening approach identified a list of 67 hydraulic fracturing-related candidate analytes based on known or suspected toxicity. Incorporation of data on potency, physicochemical properties, and environmental concentrations could further prioritize these substances for future drinking water exposure assessments or reproductive and developmental health studies.

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

PubMed

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Age factors potentiating drug toxicity in the reproductive axis

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

Walker, R.F.

Traditionally, the drug toxicity in the reproductive system has been a concern only as it affects fertility and fecundity in young individuals. The purpose of this report is to address the potential problem of synergy between drug actions and abnormal secretion of reproductive hormones that together produce disease in older individuals. Thus, reproductive toxicity has different, but no less serious implications in aging individuals. During aging, the coordinated function of elements within the reproductive neuroendocrine axis degrades. This change promotes atypical secretion of hormones producing abnormal responses in target organs and thus creates a condition with pathogenic potential. Certain drugsmore » may contribute to reproductive toxicity in aging individuals either by accelerating the process of dysregulation and/or by synergizing with hormones to stimulate pathologic changes in target tissues. The geriatric population or the world is increasing, and since it consumes a proportionately larger percentage of drugs than younger groups, this novel form of reproductive toxicity may represent a problem in drug safety that warrants serious consideration.« less

Laboratory toxicity and benthic invertebrate field colonization of Upper Columbia River sediments: Finding adverse effects using multiple lines of evidence

USGS Publications Warehouse

Fairchild, J.F.; Kemble, N.E.; Allert, A.L.; Brumbaugh, W.G.; Ingersoll, C.G.; Dowling, B.; Gruenenfelder, C.; Roland, J.L.

2012-01-01

From 1930 to 1995, the Upper Columbia River (UCR) of northeast Washington State received approximately 12 million metric tons of smelter slag and associated effluents from a large smelter facility located in Trail, British Columbia, approximately 10 km north of the United States–Canadian border. Studies conducted during the past two decades have demonstrated the presence of toxic concentrations of heavy metals in slag-based sandy sediments, including cadmium, copper, zinc, and lead in the UCR area as well as the downstream reservoir portion of Lake Roosevelt. We conducted standardized whole-sediment toxicity tests with the amphipod Hyalella azteca (28-day) and the midge Chironomus dilutus (10-day) on 11 samples, including both UCR and study-specific reference sediments. Metal concentrations in sediments were modeled for potential toxicity using three approaches: (1) probable effects quotients (PEQs) based on total recoverable metals (TRMs) and simultaneously extracted metals (SEMs); (2) SEMs corrected for acid-volatile sulfides (AVS; i.e., ∑SEM − AVS); and (3) ∑SEM − AVS normalized to the fractional organic carbon (foc) (i.e., ∑SEM − AVS/foc). The most highly metal-contaminated sample (∑PEQTRM = 132; ∑PEQSEM = 54; ∑SEM − AVS = 323; and ∑SEM − AVS/foc = 64,600 umol/g) from the UCR was dominated by weathered slag sediment particles and resulted in 80% mortality and 94% decrease in biomass of amphipods; in addition, this sample significantly decreased growth of midge by 10%. The traditional ∑AVS – SEM, uncorrected for organic carbon, was the most accurate approach for estimating the effects of metals in the UCR. Treatment of the toxic slag sediment with 20% Resinex SIR-300 metal-chelating resin significantly decreased the toxicity of the sample. Samples ∑SEM − AVS > 244 was not toxic to amphipods or midge in laboratory testing, indicating that this value may be an approximate threshold for effects in the UCR. In situ benthic invertebrate colonization studies in an experimental pond (8-week duration) indicated that two of the most metal-contaminated UCR sediments (dominated by high levels of sand-sized slag particles) exhibited decreased invertebrate colonization compared with sand-based reference sediments. Field-exposed SIR-300 resin samples also exhibited decreased invertebrate colonization numbers compared with reference materials, which may indicate behavioral avoidance of this material under field conditions. Multiple lines of evidence (analytical chemistry, laboratory toxicity, and field colonization results), along with findings from previous studies, indicate that high metal concentrations associated with slag-enriched sediments in the UCR are likely to adversely impact the growth and survival of native benthic invertebrate communities. Additional laboratory toxicity testing, refinement of the applications of sediment benchmarks for metal toxicity, and in situ benthic invertebrate studies will assist in better defining the spatial extent, temporal variations, and ecological impacts of metal-contaminated sediments in the UCR system.

Toxicity of carbon nanotubes: A review.

PubMed

Francis, Arul Prakash; Devasena, Thiyagarajan

2018-03-01

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

Predicting subtle behavioral responses of invertebrates to soil contaminants

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

Donkin, S.G.

1995-12-31

At concentration levels well below those which cause death and injury to soil invertebrates, a toxic chemical plume may yet effectively damage a soil ecosystem by triggering avoidance behavior among sensitive invertebrates as they move along the concentration gradient. The result may be a soil ecosystem lacking the benefits of effective nutrient cycling and mineralization which a thriving invertebrate population provides. While determining actual detection limits of invertebrates for chemical gradients in soils is experimentally difficult, theoretical calculations have suggested that such limits may be extremely low, and hence many organisms may sense and avoid concentrations of chemicals far belowmore » levels commonly considered acceptable. The minimum gradient (G) that can be detected by a receptor depends on the receptor radius (R), the chemical concentration (C), the diffusion constant of the chemical (D), the velocity of the organism (v), and the time over which the receptor integrates the chemical signal (t). In addition, the characteristics of that gradient are determined by interactions between the chemical and the soil particles (sorption/desorption), and advection through the pore spaces. The example of lead (Pb), a neurotoxic metal with demonstrated behavioral effects on the free-living nematode Caenorhabditis elegans, is used to model a chemical migrating through a soil. Based on experimentally determined Pb concentrations which elicited avoidance behavior in nematodes, and sorption characteristics of defined Pb-soil systems, the minimum detectable gradient (G) produced by a solubilized Pb plume in several soils was modeled. The results predict maximum allowable Pb levels in a soil if a healthy invertebrate community is desired, and suggest areas for further research into the subtle behavioral effects of environmental toxicants ore sensitive invertebrates.« less

Effects of Fruit Toxins on Intestinal and Microbial β-Glucosidase Activities of Seed-Predating and Seed-Dispersing Rodents (Acomys spp.).

PubMed

Kohl, Kevin D; Samuni-Blank, Michal; Lymberakis, Petros; Kurnath, Patrice; Izhaki, Ido; Arad, Zeev; Karasov, William H; Dearing, M Denise

2016-01-01

Plant secondary compounds (PSCs) have profound influence on the ecological interaction between plants and their consumers. Glycosides, a class of PSC, are inert in their intact form and become toxic on activation by either plant β-glucosidase enzymes or endogenous β-glucosidases produced by the intestine of the plant-predator or its microbiota. Many insect herbivores decrease activities of endogenous β-glucosidases to limit toxin exposure. However, such an adaptation has never been investigated in nonmodel mammals. We studied three species of spiny mice (Acomys spp.) that vary in their feeding behavior of the glycoside-rich fruit of Ochradenus baccatus. Two species, the common (Acomys cahirinus) and Crete (Acomys minous) spiny mice, behaviorally avoid activating glycosides, while the golden spiny mouse (Acomys russatus) regularly consumes activated glycosides. We fed each species a nontoxic diet of inert glycosides or a toxic diet of activated fruit toxins and investigated the responses of intestinal and microbial β-glucosidase activities. We found that individuals feeding on activated toxins had lower intestinal β-glucosidase activity and that the species that behaviorally avoid activating glycosides also had lower intestinal β-glucosidase activity regardless of treatment. The microbiota represented a larger source of toxin liberation, and the toxin-adapted species (golden spiny mouse) exhibited almost a fivefold increase in microbial β-glucosidase when fed activated toxins, while other species showed slight decreases. These results are contrary to those in insects, where glycoside-adapted species have lower β-glucosidase activity. The glycoside-adapted golden spiny mouse may have evolved tolerance mechanisms such as enhanced detoxification rather than avoidance mechanisms.

TOWARDS REFINED USE OF TOXICITY DATA IN STATISTICALLY BASED SAR MODELS FOR DEVELOPMENTAL TOXICITY.

EPA Science Inventory

In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

Predictive Modeling of Developmental Toxicity

EPA Science Inventory

The use of alternative methods in conjunction with traditional in vivo developmental toxicity testing has the potential to (1) reduce cost and increase throughput of testing the chemical universe, (2) prioritize chemicals for further targeted toxicity testing and risk assessment,...

Screening of toxic potential of graphene family nanomaterials using in vitro and alternative in vivo toxicity testing systems.

PubMed

Chatterjee, Nivedita; Yang, Ji Su; Park, Kwangsik; Oh, Seung Min; Park, Jeonggue; Choi, Jinhee

2015-01-01

The widely promising applications of graphene nanomaterials raise considerable concerns regarding their environmental and human health risk assessment. The aim of the current study was to evaluate the toxicity profiling of graphene family nananomaterials (GFNs) in alternative in vitro and in vivo toxicity testing models. The GFNs used in this study are graphene nanoplatelets ([GNPs]-pristine, carboxylate [COOH] and amide [NH2]) and graphene oxides (single layer [SLGO] and few layers [FLGO]). The human bronchial epithelial cells (Beas2B cells) as in vitro system and the nematode Caenorhabditis elegans as in vivo system were used to profile the toxicity response of GFNs. Cytotoxicity assays, colony formation assay for cellular toxicity and reproduction potentiality in C. elegans were used as end points to evaluate the GFNs' toxicity. In general, GNPs exhibited higher toxicity than GOs in Beas2B cells, and among the GNPs the order of toxicity was pristine>NH2>COOH. Although the order of toxicity of the GNPs was maintained in C. elegans reproductive toxicity, but GOs were found to be more toxic in the worms than GNPs. In both systems, SLGO exhibited profoundly greater dose dependency than FLGO. The possible reason of their differential toxicity lay in their distinctive physicochemical characteristics and agglomeration behavior in the exposure media. The present study revealed that the toxicity of GFNs is dependent on the graphene nanomaterial's physical forms, surface functionalizations, number of layers, dose, time of exposure and obviously, on the alternative model systems used for toxicity assessment.

Defense Science Board (DSB) Summer Study Report on Strategic Surprise

DTIC Science & Technology

2015-07-01

against changing priorities. The study focused on potential regrets in eight areas and provides recommendations to avoid strategic surprise in those...explore potential changes for  Department of Defense priorities as well as possible actions and hedges to strategic surprise and  avoid   potential  regrets ...similar surprises—and to  avoid   regretting  actions or lack  of action taken today—the study evaluated several key mission and enterprise areas. Some of

Motorcycle crashes potentially preventable by three crash avoidance technologies on passenger vehicles.

PubMed

Teoh, Eric R

2018-07-04

The objective of this study was to identify and quantify the motorcycle crash population that would be potential beneficiaries of 3 crash avoidance technologies recently available on passenger vehicles. Two-vehicle crashes between a motorcycle and a passenger vehicle that occurred in the United States during 2011-2015 were classified by type, with consideration of the functionality of 3 classes of passenger vehicle crash avoidance technologies: frontal crash prevention, lane maintenance, and blind spot detection. Results were expressed as the percentage of crashes potentially preventable by each type of technology, based on all known types of 2-vehicle crashes and based on all crashes involving motorcycles. Frontal crash prevention had the largest potential to prevent 2-vehicle motorcycle crashes with passenger vehicles. The 3 technologies in sum had the potential to prevent 10% of fatal 2-vehicle crashes and 23% of police-reported crashes. However, because 2-vehicle crashes with a passenger vehicle represent fewer than half of all motorcycle crashes, these technologies represent a potential to avoid 4% of all fatal motorcycle crashes and 10% of all police-reported motorcycle crashes. Refining the ability of passenger vehicle crash avoidance systems to detect motorcycles represents an opportunity to improve motorcycle safety. Expanding the capabilities of these technologies represents an even greater opportunity. However, even fully realizing these opportunities can affect only a minority of motorcycle crashes and does not change the need for other motorcycle safety countermeasures such as helmets, universal helmet laws, and antilock braking systems.

Chemical mixtures in untreated water from public-supply wells in the U.S. — Occurrence, composition, and potential toxicity

USGS Publications Warehouse

Toccalino, Patricia L.; Norman, Julia E.; Scott, Jonathon C.

2012-01-01

Chemical mixtures are prevalent in groundwater used for public water supply, but little is known about their potential health effects. As part of a large-scale ambient groundwater study, we evaluated chemical mixtures across multiple chemical classes, and included more chemical contaminants than in previous studies of mixtures in public-supply wells. We (1) assessed the occurrence of chemical mixtures in untreated source-water samples from public-supply wells, (2) determined the composition of the most frequently occurring mixtures, and (3) characterized the potential toxicity of mixtures using a new screening approach. The U.S. Geological Survey collected one untreated water sample from each of 383 public wells distributed across 35 states, and analyzed the samples for as many as 91 chemical contaminants. Concentrations of mixture components were compared to individual human-health benchmarks; the potential toxicity of mixtures was characterized by addition of benchmark-normalized component concentrations. Most samples (84%) contained mixtures of two or more contaminants, each at concentrations greater than one-tenth of individual benchmarks. The chemical mixtures that most frequently occurred and had the greatest potential toxicity primarily were composed of trace elements (including arsenic, strontium, or uranium), radon, or nitrate. Herbicides, disinfection by-products, and solvents were the most common organic contaminants in mixtures. The sum of benchmark-normalized concentrations was greater than 1 for 58% of samples, suggesting that there could be potential for mixtures toxicity in more than half of the public-well samples. Our findings can be used to help set priorities for groundwater monitoring and suggest future research directions for drinking-water treatment studies and for toxicity assessments of chemical mixtures in water resources.

Intersection collision avoidance using ITS countermeasures. Task 9, Intersection collision avoidance system performance guidelines

DOT National Transportation Integrated Search

2000-09-01

Phase III of the Intersection Collision Avoidance Using ITS Countermeasures program developed testbed systems, implemented the systems on a vehicle, and performed testing to determine the potential effectiveness of this system in preventing intersect...

Years of Life and Productivity Loss from Potentially Avoidable Colorectal Cancer Deaths in U.S. Counties with Lower Educational Attainment (2008–2012)

PubMed Central

Weir, Hannah K.; Li, Chunyu; Henley, S. Jane; Joseph, Djenaba

2018-01-01

Background Educational attainment (EA) is inversely associated with colorectal cancer risk. Colorectal cancer screening can save lives if precancerous polyps or early cancers are found and successfully treated. This study aims to estimate the potential productivity loss (PPL) and associated avoidable colorectal cancer–related deaths among screen-eligible adults residing in lower EA counties in the United States. Methods Mortality and population data were used to examine colorectal cancer deaths (2008–2012) among adults aged 50 to 74 years in lower EA counties, and to estimate the expected number of deaths using the mortality experience from high EA counties. Excess deaths (observed–expected) were used to estimate potential years life lost, and the human capital method was used to estimate PPL in 2012 U.S. dollars. Results County-level colorectal cancer death rates were inversely associated with county-level EA. Of the 100,857 colorectal cancer deaths in lower EA counties, we estimated that more than 21,000 (1 in 5) was potentially avoidable and resulted in nearly $2 billion annual productivity loss. Conclusions County-level EA disparities contribute to a large number of potentially avoidable colorectal cancer–related deaths. Increased prevention and improved screening potentially could decrease deaths and help reduce the associated economic burden in lower EA communities. Increased screening could further reduce deaths in all EA groups. Impact These results estimate the large economic impact of potentially avoidable colorectal cancer–related deaths in economically disadvantaged communities, as measured by lower EA. PMID:28003180

Psychological Treatments to Avoid

ERIC Educational Resources Information Center

Thomason, Timothy C.

2010-01-01

Certain psychological treatments should be avoided, and a list of such treatments would provide valuable guidance for counselors, as well as potential clients. It is well established that some therapies are potentially dangerous, and some fringe therapies are highly unlikely to help clients beyond a placebo effect. This article provides an…

Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans

PubMed Central

Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H.

2018-01-01

More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. PMID:29079228

Assessment of the application of an ecotoxicological procedure to screen illicit toxic discharges in domestic septic tank sludge.

PubMed

López-Gastey, J; Choucri, A; Robidoux, P Y; Sunahara, G I

2000-06-01

An innovative screening procedure has been developed to detect illicit toxic discharges in domestic septic tank sludge hauled to the Montreal Urban Community waste-water treatment plant. This new means of control is based on an integrative approach, using bioassays and chemical analyses. Conservative criteria are applied to detect abnormal toxicity with great reliability while avoiding false positive results. The complementary data obtained from toxicity tests and chemical analyses support the use of this efficient and easy-to-apply procedure. This study assesses the control procedure in which 231 samples were analyzed over a 30-month period. Data clearly demonstrate the deterrent power of an efficient control procedure combined with a public awareness campaign among the carriers. In the first 15 months of application, between January 1996 and March 1997, approximately 30% of the 123 samples analyzed showed abnormal toxicity. Between April 1997 and June 1998, that is, after a public hearing presentation of this procedure, this proportion dropped significantly to approximately 9% based on 108 analyzed samples. The results of a 30-month application of this new control procedure show the superior efficiency of the ecotoxicological approach compared with the previously used chemical control procedure. To be able to apply it effectively and, if necessary, to apply the appropriate coercive measures, ecotoxicological criteria should be included in regulatory guidelines.

Synthetic neurotensin analogues are nontoxic analgesics for the rabbit cornea.

PubMed

Kim, Charles; Barbut, Denise; Heinemann, Murk H; Pasternak, Gavril; Rosenblatt, Mark I

2014-05-13

To characterize the analgesic potency and toxicity of topical synthetic neurotensin analogues, and localize neurotensin receptors in the cornea and trigeminal ganglion. Cochet-Bonnet esthesiometry was performed on the rabbit cornea to test the analgesic dose response and duration of effect for two synthetic neurotensin analogues: NT71 and NT72. Receptors for neurotensin were localized in the murine cornea and trigeminal ganglion using quantitative PCR (qPCR), Western blotting, and immunohistochemistry. In vitro toxicity of NT71, NT72, and sodium channel blockers was evaluated using cytotoxicity, single-cell migration, and scratch closure assays performed on rabbit corneal epithelial cells. In vivo toxicity of these agents was assessed using a rabbit laser phototherapeutic keratectomy (PTK) model and histology. NT71 and NT72 induced potent analgesic effects on the rabbit cornea at concentrations between 1.0 and 2.5 mg/mL, lasting up to 180 minutes. A site-specific distribution of neurotensin receptors was observed in the murine cornea and trigeminal ganglion. NT71 and NT72 did not cause any significant in vitro or in vivo toxicity, in contrast to sodium channel blockers. Synthetic neurotensin analogues are potent analgesics that avoid the toxicities associated with established topical analgesic agents. Receptors for neurotensin are present in both the cornea and trigeminal ganglion. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Toxic cyanobacteria and cyanotoxins in public hot springs in Saudi Arabia.

PubMed

Mohamed, Zakaria A

2008-01-01

Toxic cyanobacteria are well reported in rivers, lakes and even marine environments, but the toxin production of cyanobacteria in hot springs is largely unexplored. Therefore, the present study investigated the presence of toxic cyanobacteria and cyanotoxins in public hot springs in Saudi Arabia. The results of an enzyme-linked immunosorbent assay (ELISA) revealed that Saudi spring cyanobacterial mats contained microcystins (MCYSTs) at concentrations ranging from 468 to 512.5 microg g(-1). The Limulus amebocyte lystae (LAL) assay detected lipopolysaccharide (LPS) endotoxins in these mats at concentrations ranging from 433.3 to 506.8 EU g(-1). MCYSTs and endotoxins were also detected in spring waters at levels of 5.7 microg l(-1) and 640 EU ml(-1), respectively, exceeding WHO's provisional guideline value for MCYST-LR in drinking-water. High-performance liquid chromatography (HPLC) analysis revealed that only Oscillatoria limosa and Synechococcus lividus can produce MCYSTs with a profile consisting of MCYST-RR and -LR. Based on the LAL assay, 12 out of 17 cyanobacterial species contained LPS at concentrations ranging from 0.93 to 21.06 EU g(-1). However, not all LPS of these species were toxic to mice. This study suggests that the hot springs in the world including Saudi Arabia should be screened for toxic cyanobacteria to avoid the exposure of people recreating and bathing in spring waters to cyanobacterial toxins.

Mg co-ordination with potential carcinogenic molecule acrylamide: Spectroscopic, computational and cytotoxicity studies

NASA Astrophysics Data System (ADS)

Singh, Ranjana; Mishra, Vijay K.; Singh, Hemant K.; Sharma, Gunjan; Koch, Biplob; Singh, Bachcha; Singh, Ranjan K.

2018-03-01

Acrylamide (acr) is a potential toxic molecule produced in thermally processed food stuff. Acr-Mg complex has been synthesized chemically and characterized by spectroscopic techniques. The binding sites of acr with Mg were identified by experimental and computational methods. Both experimental and theoretical results suggest that Mg coordinated with the oxygen atom of Cdbnd O group of acr. In-vitro cytotoxicity studies revealed significant decrease in the toxic level of acr-Mg complex as compared to pure acr. The decrease in toxicity on complexation with Mg may be a useful step for future research to reduce the toxicity of acr.

Toxicity of Nanoparticles and an Overview of Current Experimental Models.

PubMed

Bahadar, Haji; Maqbool, Faheem; Niaz, Kamal; Abdollahi, Mohammad

2016-01-01

Nanotechnology is a rapidly growing field having potential applications in many areas. Nanoparticles (NPs) have been studied for cell toxicity, immunotoxicity, and genotoxicity. Tetrazolium-based assays such as MTT, MTS, and WST-1 are used to determine cell viability. Cell inflammatory response induced by NPs is checked by measuring inflammatory biomarkers, such as IL-8, IL-6, and tumor necrosis factor, using ELISA. Lactate dehydrogenase (LDH) assay is used for cell membrane integrity. Different types of cell cultures, including cancer cell lines have been employed as in vitro toxicity models. It has been generally agreed that NPs interfere with either assay materials or with detection systems. So far, toxicity data generated by employing such models are conflicting and inconsistent. Therefore, on the basis of available experimental models, it may be difficult to judge and list some of the more valuable NPs as more toxic to biological systems and vice versa. Considering the potential applications of NPs in many fields and the growing apprehensions of FDA about the toxic potential of nanoproducts, it is the need of the hour to look for new internationally agreed free of bias toxicological models by focusing more on in vivo studies.

Short-term effects of oral administration of Pistacia lentiscus oil on tissue-specific toxicity and drug metabolizing enzymes in mice.

PubMed

Attoub, Samir; Karam, Sherif M; Nemmar, Abderrahim; Arafat, Kholoud; John, Annie; Al-Dhaheri, Wafa; Al Sultan, Mahmood Ahmed; Raza, Haider

2014-01-01

Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro. Pistacia lentiscus oil (100µl) was administered orally into mice for 5 days. Measurements of body weight did not show any weight loss. Serum concentration of LDH did not show any significant statistical difference when compared to control mice. Similarly, blood, kidney or liver function tests showed no toxicity with Pistacia lentiscus oil when compared to the control group. Examination of gastrointestinal tissues sections revealed similar structural features with no difference in cell proliferation. In this context, pharmacological dilutions of Pistacia lentiscus oil (10(-6) - 10(-3)) did not affect the viability (cell death and proliferation) of mouse gastric stem cells, human colorectal cancer cells HT29, human hepatoma cells HepG2. However, it appears that at the dose and time point studied, Pistacia lentiscus oil treatment has targeted various cytochrome P450s and has specifically inhibited the activities and the expression of CYP2E1, CYP3A4, CYP1A1 and CYP1A2 differentially in different tissues. Our results also demonstrate that there is no appreciable effect of Pistacia lentiscus oil on the GSH-dependent redox homoeostasis and detoxification mechanism in the tissues. These data suggest a good safety profile of short term oral use of Pistacia lentiscus oil as a monotherapy in the treatment of various skin, respiratory, and gastrointestinal disorders. However, due to its inhibitory effect of various cytochrome P450s and mainly CYP3A4, this might have implications on the bioavailability and metabolism of drugs taken in combination with Pistacia lentiscus oil. More attention is needed when Pistacia lentiscus oil is intended to be uses in combination with other pharmacological agents in order to avoid potential drug-drug interaction leading to toxicity. This study will help in safer use of Pistacia lentiscus oil for therapeutic purpose. © 2014 S. Karger AG, Basel.

Financial Toxicity and Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Financial Toxicity and Cancer Treatment discusses the increased financial distress that cancer patients and survivors uniquely experience. Get detailed information about the complex relationship between cancer and financial toxicity along with potential interventions in this clinician summary.

Using Spider-Web Patterns To Determine Toxicity

NASA Technical Reports Server (NTRS)

Noever, David A.; Cronise, Raymond J.; Relwani, Rachna A.

1995-01-01

Method of determining toxicities of chemicals involves recording and analysis of spider-web patterns. Based on observation spiders exposed to various chemicals spin webs that differ, in various ways, from normal webs. Potential alternative to toxicity testing on higher animals.

40 CFR 68.87 - Contractors.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.87 Contractors. (a) Application. This... known potential fire, explosion, or toxic release hazards related to the contractor's work and the... instructed in the known potential fire, explosion, or toxic release hazards related to his/her job and the...

40 CFR 68.87 - Contractors.

Code of Federal Regulations, 2012 CFR

2012-07-01

... ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.87 Contractors. (a) Application. This... known potential fire, explosion, or toxic release hazards related to the contractor's work and the... instructed in the known potential fire, explosion, or toxic release hazards related to his/her job and the...

40 CFR 68.87 - Contractors.

Code of Federal Regulations, 2014 CFR

2014-07-01

... ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.87 Contractors. (a) Application. This... known potential fire, explosion, or toxic release hazards related to the contractor's work and the... instructed in the known potential fire, explosion, or toxic release hazards related to his/her job and the...

40 CFR 68.87 - Contractors.

Code of Federal Regulations, 2013 CFR

2013-07-01

... ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.87 Contractors. (a) Application. This... known potential fire, explosion, or toxic release hazards related to the contractor's work and the... instructed in the known potential fire, explosion, or toxic release hazards related to his/her job and the...

Integration of Dosimetry, Exposure and High-Throughput Screening Data in Chemical Toxicity Assessment

EPA Science Inventory

High-throughput in vitro toxicity screening can provide an efficient way to identify potential biological targets for chemicals. However, relying on nominal assay concentrations may misrepresent potential in vivo effects of these chemicals due to differences in bioavailability, c...

Potential for metal contamination by direct sonication of nanoparticle suspensions

EPA Science Inventory

There is a growing need to examine the potential toxicity of engineered nanoparticles (ENPs) to establish regulations protective of environmental health and safety. During a series of experiments to evaluate the toxicity of titanium dioxide (TiO2) nanoparticles on terrestrial pla...

Understanding Genetic Toxicity Through Data Mining: The ...

EPA Pesticide Factsheets

This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies. This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies.

A risk assessment of topical tretinoin as a potential human developmental toxin based on animal and comparative human data.

PubMed

Johnson, E M

1997-03-01

Although topically applied all-trans-retinoic acid (tretinoin) undergoes minimal absorption and adds negligibly to normal endogenous levels, its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks. To assess the actual potential for developmental toxicity from treatment with topical tretinoin. Risk assessments were conducted on four known human developmental toxicants (valproic acid, methotrexate, thalidomide, and isotretinoin) and a potential developmental toxicant (acetylsalicylic acid). The margin of safety for each chemical was calculated from the ratio of animal no-observed adverse effect levels to human lowest-observed adverse effect levels or estimated exposure doses. The derived safety margin of more than 100 for topical tretinoin (with 2% absorption) contrasted sharply with the near unity values for valproic acid, methotrexate, thalidomide, and isotretinoin and was larger than that for acetylsalicylic acid. These data support other epidemiologic and animal data that topical tretinoin is not a potential human developmental toxicant.

Clinical grade adult stem cell banking

PubMed Central

Thirumala, Sreedhar; Goebel, W Scott

2009-01-01

There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations to formulate guidelines and standards for the quality of stem cell collection, processing, testing, banking, packaging and distribution. Clinically applicable cryopreservation and banking of adult stem cells offers unique opportunities to advance the potential uses and widespread implementation of these cells in clinical applications. Most current cryopreservation protocols include animal serum proteins and potentially toxic cryoprotectant additives (CPAs) that prevent direct use of these cells in human therapeutic applications. Long term cryopreservation of adult stem cells under good manufacturing conditions using animal product free solutions is critical to the widespread clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to avoid any potential cryoprotectant related complications, reduced CPA concentrations and efficient post-thaw washing to remove CPA are also desirable. The present review focuses on the current strategies and important aspects of adult stem cell banking for clinical applications. These include current good manufacturing practices (cGMPs), animal protein free freezing solutions, cryoprotectants, freezing & thawing protocols, viability assays, packaging and distribution. The importance and benefits of banking clinical grade adult stem cells are also discussed. PMID:20046678

Developing and regenerating a sense of taste.

PubMed

Barlow, Linda A; Klein, Ophir D

2015-01-01

Taste is one of the fundamental senses, and it is essential for our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Taste buds, which are clusters of neuroepithelial receptor cells, are housed in highly organized structures called taste papillae in the oral cavity. Whereas the overall structure of the taste periphery is conserved in almost all vertebrates examined to date, the anatomical, histological, and cell biological, as well as potentially the molecular details of taste buds in the oral cavity are diverse across species and even among individuals. In mammals, several types of gustatory papillae reside on the tongue in highly ordered arrangements, and the patterning and distribution of the mature papillae depend on coordinated molecular events in embryogenesis. In this review, we highlight new findings in the field of taste development, including how taste buds are patterned and how taste cell fate is regulated. We discuss whether a specialized taste bud stem cell population exists and how extrinsic signals can define which cell lineages are generated. We also address the question of whether molecular regulation of taste cell renewal is analogous to that of taste bud development. Finally, we conclude with suggestions for future directions, including the potential influence of the maternal diet and maternal health on the sense of taste in utero. © 2015 Elsevier Inc. All rights reserved.

Further evaluation of quantitative structure--activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens.

PubMed

Patlewicz, Grace Y; Basketter, David A; Pease, Camilla K Smith; Wilson, Karen; Wright, Zoe M; Roberts, David W; Bernard, Guillaume; Arnau, Elena Giménez; Lepoittevin, Jean-Pierre

2004-02-01

Fragrance substances represent a very diverse group of chemicals; a proportion of them are associated with the ability to cause allergic reactions in the skin. Efforts to find substitute materials are hindered by the need to undertake animal testing for determining both skin sensitization hazard and potency. One strategy to avoid such testing is through an understanding of the relationships between chemical structure and skin sensitization, so-called structure-activity relationships. In recent work, we evaluated 2 groups of fragrance chemicals -- saturated aldehydes and alpha,beta-unsaturated aldehydes. Simple quantitative structure-activity relationship (QSAR) models relating the EC3 values [derived from the local lymph node assay (LLNA)] to physicochemical properties were developed for both sets of aldehydes. In the current study, we evaluated an additional group of carbonyl-containing compounds to test the predictive power of the developed QSARs and to extend their scope. The QSAR models were used to predict EC3 values of 10 newly selected compounds. Local lymph node assay data generated for these compounds demonstrated that the original QSARs were fairly accurate, but still required improvement. Development of these QSAR models has provided us with a better understanding of the potential mechanisms of action for aldehydes, and hence how to avoid or limit allergy. Knowledge generated from this work is being incorporated into new/improved rules for sensitization in the expert toxicity prediction system, deductive estimation of risk from existing knowledge (DEREK).

Hazard-Ranking of Agricultural Pesticides for Chronic Health Effects in Yuma County, Arizona

PubMed Central

Sugeng, Anastasia J.; Beamer, Paloma I.; Lutz, Eric A.; Rosales, Cecilia B.

2013-01-01

With thousands of pesticides registered by the United States Environmental Protection Agency, it not feasible to sample for all pesticides applied in agricultural communities. Hazard-ranking pesticides based on use, toxicity, and exposure potential can help prioritize community-specific pesticide hazards. This study applied hazard-ranking schemes for cancer, endocrine disruption, and reproductive/developmental toxicity in Yuma County, Arizona. An existing cancer hazard-ranking scheme was modified, and novel schemes for endocrine disruption and reproductive/developmental toxicity were developed to rank pesticide hazards. The hazard-ranking schemes accounted for pesticide use, toxicity, and exposure potential based on chemical properties of each pesticide. Pesticides were ranked as hazards with respect to each health effect, as well as overall chronic health effects. The highest hazard-ranked pesticides for overall chronic health effects were maneb, metam sodium, trifluralin, pronamide, and bifenthrin. The relative pesticide rankings were unique for each health effect. The highest hazard-ranked pesticides differed from those most heavily applied, as well as from those previously detected in Yuma homes over a decade ago. The most hazardous pesticides for cancer in Yuma County, Arizona were also different from a previous hazard-ranking applied in California. Hazard-ranking schemes that take into account pesticide use, toxicity, and exposure potential can help prioritize pesticides of greatest health risk in agricultural communities. This study is the first to provide pesticide hazard-rankings for endocrine disruption and reproductive/developmental toxicity based on use, toxicity, and exposure potential. These hazard-ranking schemes can be applied to other agricultural communities for prioritizing community-specific pesticide hazards to target decreasing health risk. PMID:23783270

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

Tobler, Matt; Watson, Gordon; Leavitt, Dennis

Radiotherapy plays a key role in the definitive or adjuvant management of patients with mesothelioma of the pleural surface. Many patients are referred for radiation with intact lung following biopsy or subtotal pleurectomy. Delivery of efficacious doses of radiation to the pleural lining while avoiding lung parenchyma toxicity has been a difficult technical challenge. Using opposed photon fields produce doses in lung that result in moderate-to-severe pulmonary toxicity in 100% of patients treated. Combined photon-electron beam treatment, at total doses of 4250 cGy to the pleural surface, results in two-thirds of the lung volume receiving over 2100 cGy. We havemore » developed a technique using intensity-modulated photon arc therapy (IMRT) that significantly improves the dose distribution to the pleural surface with concomitant decrease in dose to lung parenchyma compared to traditional techniques. IMRT treatment of the pleural lining consists of segments of photon arcs that can be intensity modulated with varying beam weights and multileaf positions to produce a more uniform distribution to the pleural surface, while at the same time reducing the overall dose to the lung itself. Computed tomography (CT) simulation is critical for precise identification of target volumes as well as critical normal structures (lung and heart). Rotational arc trajectories and individual leaf positions and weightings are then defined for each CT plane within the patient. This paper will describe the proposed rotational IMRT technique and, using simulated isodose distributions, show the improved potential for sparing of dose to the critical structures of the lung, heart, and spinal cord.« less

The epidemiology of favism

PubMed Central

Belsey, Mark A.

1973-01-01

Favism is a potential obstacle to the use of the fava bean in the development of a locally produced, inexpensive weaning food for the Middle East and North Africa. The purposes of this study were to define the epidemiology of favism, to evaluate the advisability of using the fava bean in a weaning food, and to suggest ways of avoiding or eliminating the toxic factor in the bean. Field observations, locally acquired data, and a literature review suggested that the use of the fava bean in a weaning food would be hazardous, but that the hazard might be overcome by using certain strains of the bean or, more particularly, by using old dried beans. The disease is usually directly related in time to the harvesting and availability of fresh beans, but it is also associated with fresh dried beans. On the basis of the age distribution of the disease, patterns of bean consumption, and local food taboos it appears that the toxic factor is concentrated in the skin of the bean, that it is heat-stable, that in dried beans it decreases with age, and that it crosses into the breast milk of lactating mothers. It also appears that disease expression may be a result of the interaction of several host factors, such as nutritional status and the consumption of other foods. These observations are consistent with the results of laboratory studies, which incriminate vicine, divicine, and DOPA in the etiology of favism. PMID:4541143

National Air Toxic Assessments (NATA) Results

EPA Pesticide Factsheets

The National Air Toxics Assessment was conducted by EPA in 2002 to assess air toxics emissions in order to identify and prioritize air toxics, emission source types and locations which are of greatest potential concern in terms of contributing to population risk. This data source provides downloadable information on emissions at the state, county and census tract level.

Controllable cyanation of carbon-hydrogen bonds by zeolite crystals over manganese oxide catalyst

PubMed Central

Wang, Liang; Wang, Guoxiong; Zhang, Jian; Bian, Chaoqun; Meng, Xiangju; Xiao, Feng-Shou

2017-01-01

The synthesis of organic nitriles without using toxic cyanides is in great demand but challenging to make. Here we report an environmentally benign and cost-efficient synthesis of nitriles from the direct oxidative cyanation of primary carbon-hydrogen bonds with easily available molecular oxygen and urea. The key to this success is to design and synthesize manganese oxide catalysts fixed inside zeolite crystals, forming a manganese oxide catalyst with zeolite sheath (MnOx@S-1), which exhibits high selectivity for producing nitriles by efficiently facilitating the oxidative cyanation reaction and hindering the side hydration reaction. The work delineates a sustainable strategy for synthesizing nitriles while avoiding conventional toxic cyanide, which might open a new avenue for selective transformation of carbon-hydrogen bonds. PMID:28504259

The use of a behavioral response system in the USF/NASA toxicity screening test method

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Cumming, H. J.; Packham, S. C.

1977-01-01

Relative toxicity data on the pyrolysis effluents from bisphenol A polycarbonate and wool fabric were obtained, based on visual observations of the behavior of free-moving mice and on an avoidance response behavioral paradigm of restrained rats monitored by an instrumented behavioral system. The initial experiments show an essentially 1:1 correlation between the two systems with regard to first signs of incapacitation, collapse, and death from pyrolysis effluents from polycarbonate. It is hypothesized that similarly good correlations between these two systems might exist for other materials exhibiting predominantly carbon monoxide mechanisms of intoxication. This hypothesis needs to be confirmed, however, by additional experiments. Data with wool fabric exhibited greater variability with both procedures, indicating possibly different mechanisms of intoxication for wool as compared with bisphenol A polycarbonate.

Understanding approach and avoidance in verbal descriptions of everyday actions: An ERP study.

PubMed

Marrero, Hipólito; Urrutia, Mabel; Beltrán, David; Gámez, Elena; Díaz, José M

2017-06-01

Understanding verbal descriptions of everyday actions could involve the neural representation of action direction (avoidance and approach) toward persons and things. We recorded the electrophysiological activity of participants while they were reading approach/avoidance action sentences that were directed toward a target: a thing/a person (i.e., "Petra accepted/rejected Ramón in her group"/ "Petra accepted/rejected the receipt of the bank"). We measured brain potentials time locked to the target word. In the case of things, we found a N400-like component with right frontal distribution modulated by approach/avoidance action. This component was more negative in avoidance than in approach sentences. In the case of persons, a later negative event-related potential (545-750 ms) with left frontal distribution was sensitive to verb direction, showing more negative amplitude for approach than avoidance actions. In addition, more negativity in approach-person sentences was associated with fear avoidance trait, whereas less negativity in avoidance-person sentences was associated with a greater approach trait. Our results support that verbal descriptions of approach/avoidance actions are encoded differently depending on whether the target is a thing or a person. Implications of these results for a social, emotional and motivational understanding of action language are discussed.

Victimization and depressive symptomology in transgender adults: The mediating role of avoidant coping

PubMed Central

Hughto, Jaclyn M. White; Pachankis, John E.; Willie, Tiara C.; Reisner, Sari L.

2016-01-01

Victimization and depressive distress symptoms represent serious and interconnected public health problems facing transgender communities. Avoidant coping is hypothesized to temporarily alleviate the stress of victimization, but has potential long-term mental and behavioral health costs, such as increasing the probability of depressive symptoms. A community sample of 412 transgender adults (M age = 32.7, SD = 12.8) completed a one-time survey capturing multiple forms of victimization (i.e., everyday discrimination, bullying, physical assault by family, verbal harassment by family, childhood sexual abuse, intimate partner violence), avoidant coping, and past-week depressive symptomology. Structural equation modeling examined the mediating role of avoidant coping in the association between victimization and depressive symptomology. A latent victimization variable composed of six measures of victimization was positively associated with avoidant coping, which in turn was positively associated with depressive symptoms. Victimization was also positively associated with depressive symptomology both directly and indirectly through avoidant coping. Avoidant coping represents a potentially useful intervention target for clinicians aiming to reduce the mental health sequelae of victimization in this highly stigmatized and vulnerable population. PMID:28068130

Control of Sand Flies with Attractive Toxic Sugar Baits (ATSB) and Potential Impact on Non-Target Organisms in Morocco

DTIC Science & Technology

2015-02-08

dinotefuran has successful con- trolled Culex and Aedes spp. in similar field sites in Morocco [22]. However, this if the first report of the use of...et al. Control of Aedes abopttus with attractive toxic sugar baits (A TSB) and potential Impact on non target organisms In St. Augustine, Florida...of Anopheles sergenti and Aedes CO!Pk.JS populations following presentation of attractive toxic (splnosad) sugar bait stations In an oasis. J Am

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...

Toxico-Cheminformatics: New and Expanding Public Resources to Support Chemical Toxicity Assessments

EPA Science Inventory

High-throughput screening (HTS) technologies, along with efforts to improve public access to chemical toxicity information resources and to systematize older toxicity studies, have the potential to significantly improve information gathering efforts for chemical assessments and p...

SMOG-CHAMBER TOXICOLOGY BETTER ESTIMATES THE TRUE TOXIC POTENTIAL OF ATMOSPHERIC MIXTURES

EPA Science Inventory

The chemistry of hazardous air pollutants (HAPs) have been studied for many years, yet little is known about how these chemicals, once interacted with urban atmospheres, affect healthy and susceptible individuals. The toxic potential of these very reactive compounds once they int...

The Analysis of Genomic Dose-Response Data in the EPA ToxCast™ Program

EPA Science Inventory

The U.S. EPA must assess the potential adverse effects of thousands of chemicals, often with limited toxicity information. Accurate toxicity predictions will help prioritize chemicals for further testing, focusing resources on the greater potential hazards or risks. In vitro geno...

Acute Toxicity of Ternary Cd-Cu-Ni and Cd-Ni-Zn Mixtures to Daphnia magna: Dominant Metal Pairs Change along a Concentration Gradient.

PubMed

Traudt, Elizabeth M; Ranville, James F; Meyer, Joseph S

2017-04-18

Multiple metals are usually present in surface waters, sometimes leading to toxicity that currently is difficult to predict due to potentially non-additive mixture toxicity. Previous toxicity tests with Daphnia magna exposed to binary mixtures of Ni combined with Cd, Cu, or Zn demonstrated that Ni and Zn strongly protect against Cd toxicity, but Cu-Ni toxicity is more than additive, and Ni-Zn toxicity is slightly less than additive. To consider multiple metal-metal interactions, we exposed D. magna neonates to Cd, Cu, Ni, or Zn alone and in ternary Cd-Cu-Ni and Cd-Ni-Zn combinations in standard 48 h lethality tests. In these ternary mixtures, two metals were held constant, while the third metal was varied through a series that ranged from nonlethal to lethal concentrations. In Cd-Cu-Ni mixtures, the toxicity was less than additive, additive, or more than additive, depending on the concentration (or ion activity) of the varied metal and the additivity model (concentration-addition or independent-action) used to predict toxicity. In Cd-Ni-Zn mixtures, the toxicity was less than additive or approximately additive, depending on the concentration (or ion activity) of the varied metal but independent of the additivity model. These results demonstrate that complex interactions of potentially competing toxicity-controlling mechanisms can occur in ternary-metal mixtures but might be predicted by mechanistic bioavailability-based toxicity models.

Probing nanomechanical interaction at the interface between biological membrane and potentially toxic chemical.

PubMed

Lim, Chanoong; Park, Sohee; Park, Jinwoo; Ko, Jina; Lee, Dong Woog; Hwang, Dong Soo

2018-04-12

Various xenobiotics interact with biological membranes, and precise evaluations of the molecular interactions between them are essential to foresee the toxicity and bioavailability of existing or newly synthesized molecules. In this study, surface forces apparatus (SFA) measurement and Langmuir trough based tensiometry are performed to reveal nanomechanical interaction mechanisms between potential toxicants and biological membranes for ex vivo toxicity evaluation. As a toxicant, polyhexamethylene guanidine (PHMG) was selected because PHMG containing humidifier disinfectant and Vodka caused lots of victims in both S. Korea and Russia, respectively, due to the lack of holistic toxicity evaluation of PHMG. Here, we measured strong attraction (Wad ∼4.2 mJ/m 2 ) between PHMG and head group of biological membranes while no detectable adhesion force between the head group and control molecules was measured. Moreover, significant changes in π-A isotherm of 1,2-Dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) monolayers were measured upon PHMG adsorption. These results indicate PHMG strongly binds to hydrophilic group of lipid membranes and alters the structural and phase behavior of them. More importantly, complementary utilization of SFA and Langmuir trough techniques are found to be useful to predict the potential toxicity of a chemical by evaluating the molecular interaction with biological membranes, the primary protective barrier for living organisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Smoking-Specific Experiential Avoidance is Indirectly Associated with Trait Worry and Smoking Processes among Treatment-Seeking Smokers.

PubMed

Farris, Samantha G; Zvolensky, Michael J; Norton, Peter J; Hogan, Julianna; Smith, Angela H; Talkovsky, Alexander M; Garey, Lorra; Schmidt, Norman B

2016-01-01

Limited work has examined worry, or apprehensive anticipation about future negative events, in terms of smoking. One potential explanatory factor is the tendency to respond inflexibly and with avoidance in the presence of smoking-related distress (smoking-specific experiential avoidance). Participants (n = 465) were treatment-seeking daily smokers. Cross-sectional (pre-treatment) self-report data were utilized to assess trait worry, smoking-specific experiential avoidance, and four smoking criterion variables: nicotine dependence, motivational aspects of quitting, perceived barriers to smoking cessation, and severity of problematic symptoms reported in past quit attempts. Trait worry was significantly associated with greater levels of nicotine dependence, motivation to quit smoking, perceived barriers for smoking cessation, and more severe problems while quitting in the past; associations occurred indirectly through higher levels of smoking-specific experiential avoidance. Findings provide initial support for the potential role of smoking-specific experiential avoidance in explaining the association between trait worry and a variety of smoking processes.