Sample records for compound toxicity based

  1. Investigation on modes of toxic action to rats based on aliphatic and aromatic compounds and comparison with fish toxicity based on exposure routes. (United States)

    He, Jia; Li, Jin J; Wen, Yang; Tai, Hong W; Yu, Yang; Qin, Wei C; Su, Li M; Zhao, Yuan H


    The modes of toxic action (MOAs) play an important role in the assessment of the ecotoxicity of organic pollutants. However, few studies have been reported on the MOAs in rat toxicity. In this paper, the toxic contributions of functional groups in 1255 aromatic compounds were calculated from regression and were then compared with the toxic contributions in aliphatic compounds. The results show that some functional groups have same toxic contributions both in aromatic and aliphatic compounds, but some have not. To investigate the MOAs in rat toxicity, the distribution of toxic ratio (TR) was examined for well-known baseline and less inert compounds and thresholds of log TR=0.3 and 0.5 were used to classify baseline, less inert and reactive compounds. The results showed that some compounds identified as baseline compounds in fish toxicity were also classified as baseline compounds in rat toxicity. Except for phenols and anilines which were identified as less inert compounds in fish toxicity, aromatic compounds with functional groups such as ether, nitrile, nitrophenol, isocyanatoe and chloro were identified as less inert chemicals in rat toxicity. Reactive compounds identified in fish toxicity exhibit greater toxicity to rats. These compounds can undergo nucleophilic substitution, acylation and Schiff base formation with biological macromolecules. The critical body residues (CBRs) calculated from absorption and bioconcentration show that log 1/CBRs in rat toxicity are not equal to that in fish for some compounds. It suggests that the exposure route can affect the identification of MOAs between these two species for these compounds.

  2. Toxic compounds in honey. (United States)

    Islam, Md Nazmul; Khalil, Md Ibrahim; Islam, Md Asiful; Gan, Siew Hua


    There is a wealth of information about the nutritional and medicinal properties of honey. However, honey may contain compounds that may lead to toxicity. A compound not naturally present in honey, named 5-hydroxymethylfurfural (HMF), may be formed during the heating or preservation processes of honey. HMF has gained much interest, as it is commonly detected in honey samples, especially samples that have been stored for a long time. HMF is a compound that may be mutagenic, carcinogenic and cytotoxic. It has also been reported that honey can be contaminated with heavy metals such as lead, arsenic, mercury and cadmium. Honey produced from the nectar of Rhododendron ponticum contains alkaloids that can be poisonous to humans, while honey collected from Andromeda flowers contains grayanotoxins, which can cause paralysis of limbs in humans and eventually leads to death. In addition, Melicope ternata and Coriaria arborea from New Zealand produce toxic honey that can be fatal. There are reports that honey is not safe to be consumed when it is collected from Datura plants (from Mexico and Hungary), belladonna flowers and Hyoscamus niger plants (from Hungary), Serjania lethalis (from Brazil), Gelsemium sempervirens (from the American Southwest), Kalmia latifolia, Tripetalia paniculata and Ledum palustre. Although the symptoms of poisoning due to honey consumption may differ depending on the source of toxins, most common symptoms generally include dizziness, nausea, vomiting, convulsions, headache, palpitations or even death. It has been suggested that honey should not be considered a completely safe food.

  3. Toxicity of platinum compounds. (United States)

    Hartmann, Jörg Thomas; Lipp, Hans-Peter


    Since the introduction of platinum-based combination chemotherapy, particularly cisplatin, the outcome of the treatment of many solid tumours has changed. The leading platinum compounds in cancer chemotherapy are cisplatin, carboplatin and oxaliplatin. They share some structural similarities; however, there are marked differences between them in therapeutic use, pharmacokinetics and adverse effects profiles [1-4]. Compared to cisplatin, carboplatin has inferior efficacy in germ-cell tumour, head and neck cancer and bladder and oesophageal carcinoma, whereas both drugs seem to have comparable efficacy in advanced non-small cell and small cell lung cancer as well as ovarian cancer [5-7]. Oxaliplatin belongs to the group of diaminocyclohexane platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid [8,9]. Other platinum compounds such as oral JM216, ZD0473, BBR3464 and SPI-77, which is a pegylated liposomal formulation of cisplatin, are still under investigation [10-13], whereas nedaplatin has been approved in Japan for the treatment of non-small cell lung cancer and other solid tumours. This review focuses on cisplatin, carboplatin and oxaliplatin.

  4. Polyoxometalate-based Catalysts for Toxic Compound Decontamination and Solar Energy Conversion (United States)

    Guo, Weiwei

    Polyoxometalates (POMs) have been attracting interest from researchers in the fields of Inorganic Chemistry, Physical Chemistry, Biomolecular Chemistry, etc. Their unique structures and properties render them versatile and facilitate applications in medicine, magnetism, electrochemistry, photochemistry and catalysis. In particular, toxic compound (chemical warfare agents (CWAs) and toxic industrial compounds (TICs)) decontamination and solar energy conversion by POM-based materials have becoming promising and important research areas that deserve much attention. The focus of this thesis is to explore the structural features of POMs, to develop POM-based materials and to investigate their applications in toxic compound decontamination and solar energy conversion. The first part of this thesis gives a general introduction on the history, structures, properties and applications of POMs. The second part reports the synthesis, structures, and reactivity of different types of POMs in the destruction of TICs and CWAs. Three tetra-n-butylammonium (TBA) salts of polyvanadotungstates, [n-Bu4N]6[ PW9V3], [n-Bu4N] 5H2PW8V4O40 (PW 8V4), [n-Bu4N]4H 5PW6V6O40· 20H2O (PW6V6) are discussed in detail. These vanadium-substituted Keggin type POMs show effective activity for the aerobic oxidation of formaldehyde (a major TIC and human-environment carcingen) to formic acid under ambient conditions. Moreover, two types of POMs have also been developed for the removal of CWAs and/or their simulants. Specifically, a layered manganese(IV)-containing heteropolyvanadate with a 1:14 Stoichiometry, K4Li2[MnV14O40]˙21H2 O has been prepared. Its catalytic activity for oxidative removal of 2-chloroethyl ethyl sulfide (a mustard simulant) is discussed. The second type of POM developed for decontamination of CWAs and their simulants is the new one-dimensional polymeric polyniobate (P-PONb), K12[Ti 2O2][GeNb12O40]˙19H2O (KGeNb). The complex has been applied to the decontamination of a wide range

  5. A quantum chemical based toxicity study of estimated reduction potential and hydrophobicity in series of nitroaromatic compounds. (United States)

    Gooch, A; Sizochenko, N; Sviatenko, L; Gorb, L; Leszczynski, J


    Nitroaromatic compounds and the products of their degradation are toxic to bacteria, cells and animals. Various studies have been carried out to better understand the mechanism of toxicity of aromatic nitrocompounds and their relationship to humans and the environment. Recent data relate cytotoxicity of nitroaromatic compounds to their single- or two-electron enzymatic reduction. However, mechanisms of animal toxicity could be more complex. This work investigates the estimated reduction and oxidation potentials of 34 nitroaromatic compounds using quantum chemical approaches. All geometries were optimized with density functional theory (DFT) using the solvation model based on density (SMD) and polarizable continuum model (PCM) solvent model protocols. Quantitative structure-activity/property (QSAR/QSPR) models were developed using descriptors obtained from quantum chemical optimizations as well as the DRAGON software program. The QSAR/QSPR equations developed consist of two to four descriptors. Correlations have been identified between electron affinity (ELUMO) and hydrophobicity (log P).

  6. Weighted Feature Significance: A Simple, Interpretable Model of Compound Toxicity Based on the Statistical Enrichment of Structural Features


    Huang, Ruili; Southall, Noel; Xia, Menghang; Cho, Ming-Hsuang; Jadhav, Ajit; Nguyen, Dac-Trung; Inglese, James; Tice, Raymond R.; Austin, Christopher P.


    In support of the U.S. Tox21 program, we have developed a simple and chemically intuitive model we call weighted feature significance (WFS) to predict the toxicological activity of compounds, based on the statistical enrichment of structural features in toxic compounds. We trained and tested the model on the following: (1) data from quantitative high–throughput screening cytotoxicity and caspase activation assays conducted at the National Institutes of Health Chemical Genomics Center, (2) dat...

  7. Feasibility of application of conductometric biosensor based on acetylcholinesterase for the inhibitory analysis of toxic compounds of different nature. (United States)

    Stepurska, K V; Soldatkin, Capital O Cyrillic О; Kucherenko, I S; Arkhypova, V M; Dzyadevych, S V; Soldatkin, A P


    This study was aimed at the development of a conductometric biosensor based on acetylcholinesterase considering the feasibility of its application for the inhibitory analysis of various toxicants. In this paper, the optimum conditions for enzyme immobilization on the transducer surface are selected as well as the optimum concentration of substrate for inhibitory analysis. Sensitivity of the developed biosensor to different classes of toxic compounds (organophosphorus pesticides, heavy metal ions, surfactants, aflatoxin, glycoalkaloids) was tested. It is shown that the developed biosensor can be successfully used for the analysis of pesticides and mycotoxins, as well as for determination of total toxicity of the samples. A new method of biosensor analysis of toxic substances of different classes in complex multicomponent aqueous samples is proposed.

  8. Reproductive toxicities of methoxychlor based on estrogenic properties of the compound and its estrogenic metabolite, hydroxyphenyltrichloroethane. (United States)

    Aoyama, Hiroaki; Chapin, Robert E


    Methoxychlor is an organochlorine pesticide having a weak estrogenicity, which is estimated to be approximately 1000- to 14,000-fold less potent to a natural ligand, 17β-estradiol. However, its active metabolite, hydroxyphenyltrichloroethane, has much more potent estrogenic activity and probably acts in the target organs of animals exposed to methoxychlor at least 100 times stronger than the parent compound. A variety of in vivo reproductive toxicity studies have shown that treatment with methoxychlor exerts typical endocrine-disrupting effects manifest as estrogenic effects, such as formation of cystic ovaries resulting in ovulation failures, uterine hypertrophy, hormonal imbalances, atrophy of male sexual organs, and deteriorations of sperm production in rats and/or mice, through which it causes serious reproductive damages in both sexes of animals at sufficient dose levels. However, methoxychlor is not teratogenic. The no-observed-adverse-effect level of methoxychlor among reliable experimental animal studies in terms of the reproductive toxicity is 10 ppm (equivalent to 0.600 mg/kg/day) in a two-generation reproduction toxicity study.

  9. Toxicity of dipyridyl compounds and related compounds. (United States)

    Li, Shenggang; Crooks, Peter A; Wei, Xiaochen; de Leon, Jose


    Five dipyridyl isomers, 2,2'-, 2,3'-, 2,4'-, 3,3'-, and 4,4'-dipyridyl, are products resulting from the pyrolytic degradation of tobacco products and degradation of the herbicide paraquat, and therefore may be present in the environment. In this article, the toxicological properties of these dipyridyl isomers in humans and animals are reviewed. Epidemiological studies suggest that cancerous skin lesions in workers involved in the manufacturing of paraquat may be associated with exposure to dipyridyl compounds. Experimental animal studies suggest that dipyridyl isomers may have several toxicological effects. Three of the dipyridyl isomers (the 2,2', 2,4', and 4,4' isomers) appear to be inducers of some metabolic enzymes. The 2,2'-dipyridyl isomer, an iron chelator, appears to influence vasospasm in primate models of stroke. The cytotoxic effects of 2,2'-dipyridyl on several leukemia cell lines have been reported, and a potent teratogenic effect of 2,2'-dipyridyl has been observed in rats. Based on the results of paraquat studies in experimental animal models, it has been proposed that paraquat may have deleterious effects on dopaminergic neurons. These findings support the epidemiological evidence that paraquat exposure may be associated with the development of Parkinson's disease. Studies designed to determine an association between paraquat exposure and Parkinson's disease are complicated by the possibility that metabolic changes may influence the neurotoxicity of paraquat and/or its metabolites. Preliminary unpublished data in mice show that 300-mg/kg doses of 2,2'-dipyridyl are neurotoxic, and 300-mg/kg doses of 2,4'- and 4,4'-dipyridyls are lethal. These results are consistent with earlier studies in Sherman rats using high 2,2'- and 4,4'-dipyridyl doses. New studies are needed to further explore the toxicological properties of dipyridyls and their potential public health impact.

  10. Nanoengineered Carbon-Based Materials For Reactive Adsorption of Toxic Industrial Compounds (United States)


    ChemSusChem, (03 2011): 0. doi: 10.1002/cssc.201000296 Camille Petit, Teresa J. Bandosz. Synthesis , Characterization, and Ammonia Adsorption...Bandosz. The synthesis and characterization of copper-based metal organic framework/graphene composites, Carbon, (9 2010): . doi: C. Petit, B...Mendoza, T.J. Bandosz. Reactive adsorption of ammonia on Cu-based MOF /graphene composites , Langmuir, (7 2010): . doi: Kavindra Singh, Nikolina A

  11. Medical Applications and Toxicities of Gallium Compounds

    Directory of Open Access Journals (Sweden)

    Christopher R. Chitambar


    Full Text Available Over the past two to three decades, gallium compounds have gained importance in the fields of medicine and electronics. In clinical medicine, radioactive gallium and stable gallium nitrate are used as diagnostic and therapeutic agents in cancer and disorders of calcium and bone metabolism. In addition, gallium compounds have displayed anti-inflammatory and immunosuppressive activity in animal models of human disease while more recent studies have shown that gallium compounds may function as antimicrobial agents against certain pathogens. In a totally different realm, the chemical properties of gallium arsenide have led to its use in the semiconductor industry. Gallium compounds, whether used medically or in the electronics field, have toxicities. Patients receiving gallium nitrate for the treatment of various diseases may benefit from such therapy, but knowledge of the therapeutic index of this drug is necessary to avoid clinical toxicities. Animals exposed to gallium arsenide display toxicities in certain organ systems suggesting that environmental risks may exist for individuals exposed to this compound in the workplace. Although the arsenic moiety of gallium arsenide appears to be mainly responsible for its pulmonary toxicity, gallium may contribute to some of the detrimental effects in other organs. The use of older and newer gallium compounds in clinical medicine may be advanced by a better understanding of their mechanisms of action, drug resistance, pharmacology, and side-effects. This review will discuss the medical applications of gallium and its mechanisms of action, the newer gallium compounds and future directions for development, and the toxicities of gallium compounds in current use.

  12. A proposal for calculating the no-observed-adverse-effect level (NOAEL) for organic compounds responsible for liver toxicity based on their physicochemical properties


    Marek Jakubowski; Sławomir Czerczak


    Objectives: Both environmental and occupational exposure limits are based on the no-observed-adverse-effect level (NOAEL), lowest-observed-adverse-effect level (LOAEL) or benchmark dose (BMD) deriving from epidemiological and experimental studies. The aim of this study is to investigate to what extent the NOAEL values for organic compounds responsible for liver toxicity calculated based on their physicochemical properties could be used for calculating occupational exposure limits. Material an...

  13. A proposal for calculating the no-observed-adverse-effect level (NOAEL for organic compounds responsible for liver toxicity based on their physicochemical properties

    Directory of Open Access Journals (Sweden)

    Marek Jakubowski


    Full Text Available Objectives: Both environmental and occupational exposure limits are based on the no-observed-adverse-effect level (NOAEL, lowest-observed-adverse-effect level (LOAEL or benchmark dose (BMD deriving from epidemiological and experimental studies. The aim of this study is to investigate to what extent the NOAEL values for organic compounds responsible for liver toxicity calculated based on their physicochemical properties could be used for calculating occupational exposure limits. Material and Methods: The distribution coefficients from air to the liver (log Kliver were calculated according to the Abraham solvation equation. NOAEL and LOAEL values for early effects in the liver were obtained from the literature data. The descriptors for Abraham's equation were found for 59 compounds, which were divided into 2 groups: "non-reactive" (alcohols, ketones, esters, ethers, aromatic and aliphatic hydrocarbons, amides and "possibly reactive" (aldehydes, allyl compounds, amines, benzyl halides, halogenated hydrocarbons, acrylates. Results: The correlation coefficients between log-log K and log NOAEL for non-reactive and reactive compounds amounted to r = -0.8123 and r = -0.8045, respectively, and were statistically significant. It appears that the Abraham equation could be used to predict the NOAEL values for compounds lacking information concerning their liver toxicity. Conclusions: In view of the tendency to limit animal testing procedures, the method proposed in this paper can improve the practice of setting exposure guidelines for the unstudied compounds.

  14. Modeling toxic compounds from nitric oxide emission measurements (United States)

    Vallero, Daniel A.; Peirce, Jeffrey; Cho, Ki Don

    Determining the amount and rate of degradation of toxic pollutants in soil and groundwater is difficult and often requires invasive techniques, such as deploying extensive monitoring well networks. Even with these networks, degradation rates across entire systems cannot readily be extrapolated from the samples. When organic compounds are degraded by microbes, especially nitrifying bacteria, oxides or nitrogen (NO x) are released to the atmosphere. Thus, the flux of nitric oxide (NO) from the soil to the lower troposphere can be used to predict the rate at which organic compounds are degraded. By characterizing and applying biogenic and anthropogenic processes in soils the rates of degradation of organic compounds. Toluene was selected as a representative of toxic aromatic compounds, since it is inherently toxic, it is a substituted benzene compound and is listed as a hazardous air pollutant under Section 12 of the Clean Air Act Amendments of 1990. Measured toluene concentrations in soil, microbial population growth and NO fluxes in chamber studies were used to develop and parameterize a numerical model based on carbon and nitrogen cycling. These measurements, in turn, were used as indicators of bioremediation of air toxic (i.e. toluene) concentrations. The model found that chemical concentration, soil microbial abundance, and NO production can be directly related to the experimental results (significant at P hydrocarbons and oxides of nitrogen. As such, the model may be a tool for decision makers in ozone non-attainment areas.

  15. [Platinum compounds: metabolism, toxicity and supportive strategies]. (United States)

    Lipp, H P; Hartmann, J T


    Although the leading platinum compounds, cisplatin, carboplatin, and oxaliplatin, share some structural similarities, there are marked differences between them in therapeutic uses, pharmacokinetics, and adverse effects profiles. Compared with cisplatin, carboplatin has inferior efficacy in germ-cell tumors, head and neck cancers, and bladder and esophageal carcinomas, whereas the two drugs appear to have comparable efficacy in ovarian cancer, extensive small-cell lung cancers (SCLC), and advanced non-small-cell lung cancers (NSCLC). Oxaliplatin belongs to the group of diaminocyclohexane (DACH) platinum compounds. It is the first platinum-based drug that has marked efficacy in colorectal cancer when given in combination with 5-fluorouracil and folinic acid. Nedaplatin has been registered in Japan, whereas other derivatives, like JM216 (which is the only orally available platinum derivative), ZD0473, BBR3464, and SPI-77 (a liposomal formulation of cisplatin), are still under investigation. The adverse effects of platinum compounds are reviewed together with possible prevention strategies.

  16. Toxic effects of copper-based nanoparticles or compounds to lettuce (Lactuca sativa) and alfalfa (Medicago sativa). (United States)

    Hong, Jie; Rico, Cyren M; Zhao, Lijuan; Adeleye, Adeyemi S; Keller, Arturo A; Peralta-Videa, Jose R; Gardea-Torresdey, Jorge L


    The increased production and use of nanoparticles (NPs) has generated concerns about their impact on living organisms. In this study, nCu, bulk Cu, nCuO, bulk CuO, Cu(OH)2 (CuPRO 2005, Kocide 3000), and CuCl2 were exposed for 15 days to 10 days-old hydroponically grown lettuce (Lactuca sativa) and alfalfa (Medicago sativa). Each compound was applied at 0, 5, 10, and 20 mg L(-1). At harvest, we measured the size of the plants and determined the concentration of Cu, macro and microelements by using ICP-OES. Catalase and ascorbate peroxidase activity was also determined. Results showed that all Cu NPs/compounds reduced the root length by 49% in both plant species. All Cu NPs/compounds increased Cu, P, and S (>100%, >50%, and >20%, respectively) in alfalfa shoots and decreased P and Fe in lettuce shoot (>50% and >50%, respectively, excluding Fe in CuCl2 treatment). Biochemical assays showed reduced catalase activity in alfalfa (root and shoot) and increased ascorbate peroxidase activity in roots of both plant species. Results suggest that Cu NPs/compounds not only reduced the size of the plants but altered nutrient content and enzyme activity in both plant species.

  17. Mammalian Toxicity of Munitions Compounds. Summary of Toxicity of Nitrotoluenes (United States)


    Allargenicity Carcinogenicty Mutagenicity Reproductive toxicity Disposition Metabolism Excretion Risk Asseasment Water Quality Criterion UCU1flY...16 E. Water Quality Criterion .............. ... 17 References ................ ........................... .... 19 xii • I II’ I TABLE OF...including mixtures, are produced commercially in large quantities. They are reduced to diaminotoluenes , reacted with phosgene to make toluenediisocyanate

  18. Toxicity prediction of compounds from turmeric (Curcuma longa L). (United States)

    Balaji, S; Chempakam, B


    Turmeric belongs to the ginger family Zingiberaceae. Currently, cheminformatics approaches are not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which does not have any toxic effects. In the present study, toxicity of 200 chemical compounds from turmeric were predicted (includes bacterial mutagenicity, rodent carcinogenicity and human hepatotoxicity). The study shows out of 200 compounds, 184 compounds were predicted as toxigenic, 136 compounds are mutagenic, 153 compounds are carcinogenic and 64 compounds are hepatotoxic. To cross validate our results, we have chosen the popular curcumin and found that curcumin and its derivatives may cause dose dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric which are non-mutagenic, non-carcinogenic, non-hepatotoxic, and do not have any side-effects. Hence, the cost-effective approach presented in this paper could be used to filter toxic compounds from the drug discovery lifecycle.

  19. Chemoproteomics-based design of potent LRRK2-selective lead compounds that attenuate Parkinson's disease-related toxicity in human neurons (United States)

    Ramsden, Nigel; Perrin, Jessica; Ren, Zhao; Lee, Byoung Dae; Zinn, Nico; Dawson, Valina L.; Tam, Danny; Bova, Michael; Delling, Manja; Drewes, Gerard; Bantscheff, Marcus; Bard, Frederique; Dawson, Ted M.; Hopf, Carsten


    Leucine-rich repeat kinase-2 (LRRK2) mutations are the most important cause of familial Parkinson's disease and non-selective inhibitors are protective in rodent disease models. Due to their poor potency and selectivity, the neuroprotective mechanism of these tool compounds has remained elusive so far and it is still unknown whether selective LRRK2 inhibition can attenuate mutant LRRK2-dependent toxicity in human neurons. Here, we employ a chemoproteomics strategy to identify potent, selective and metabolically stable LRRK2 inhibitors. We demonstrate that CZC-25146 prevents mutant LRRK2-induced injury of cultured rodent and human neurons with mid-nanomolar potency. These precise chemical probes further validate this emerging therapeutic strategy. They will enable more detailed studies of LRRK2-dependent signaling and pathogenesis and accelerate drug discovery. PMID:21812418

  20. Sorption of toxic organic compounds on wastewater solids: Mechanism and modeling

    Energy Technology Data Exchange (ETDEWEB)

    Wang, L.; Govind, R.; Dobbs, R.A.


    Sorption of toxic organic compounds on wastewater solids is an important process in conventional biological wastewater treatment systems. The extent of accumulation of toxic organic compounds by sorption onto wastewater solids not only affects the efficiency of the treatment system, but also impacts the management of wastewater solids. The study is an attempt to propose a mechanism for understanding the sorption phenomenon and to develop a model for sorption on wastewater solids based on the proposed mechanism. It was postulated that sorption was a combination of two processes: adsorption and partitioning. A sorption model was developed for both single component and multicomponent systems. The model was tested using single component experimental isotherm data of eight toxic organic compounds.

  1. Toxicity of Myristica fagrans seed compounds against Blattella germanica (Dictyoptera: Blattellidae). (United States)

    Jung, Woo-Chul; Jang, Young-Su; Hieu, Tran Trung; Lee, Chong-Kyu; Ahn, Young-Joon


    The insecticidal constituents of hexane-soluble fraction from a methanolic extract of the seeds from Myristica fragrans (Myristicaceae) against adult females of Blattella germanica (L.) (Dictyoptera: Blattellidae) were analyzed by gas chromatography and gas chromatography-mass spectrometry. The insecticidal activity of 13 Myristica seed compounds against female B. germanica was examined by using the filter-paper contact toxicity and vapor phase toxicity bioassays. Results were compared with those of the other 23 known compounds of Myristica seed and currently used insecticides: dichlorvos, deltamethrin, permethrin, and propoxur. In contact toxicity tests using female B. germanica, (IS)-(-) -beta-pinene (0.06 mg/cm2) was the most toxic insecticide, based on 24-h LD50 values. The insecticidal activity of this compound was comparable with that of permethrin (0.05 mg/cm2). (1R)-(+) -Camphor, (1S)-(-) -camphor, dipentene, (1R)-(+) -3-pinene, and (+)-alpha-terpineol (0.10-0.14 mg/cm2) were more toxic than propoxur (0.19 mg/cm2). (E)-Sabinene hydrate and propoxur were almost equitoxic. Potent insecticidal activity also was observed with (R)-(+) -citronellal, (S)-(-) -citronellal, (R)-(-) -alpha-phellandrene, (1S)-(-) -alpha-pinene, (1R)-(+) -alpha-pinene, and safrole (0.27-0.48 mg/cm2). In vapor phase toxicity tests, the compounds tested were effective in closed but not in open containers. These results indicate that the effect of these compounds was largely a result of action in the vapor phase. Myristica seed compounds described merit further study as potential insecticides or as leads for the control of cockroaches.

  2. Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test. (United States)

    Jomaa, Barae; Hermsen, Sanne A B; Kessels, Maurijn Y; van den Berg, Johannes H J; Peijnenburg, Ad A C M; Aarts, Jac M M J G; Piersma, Aldert H; Rietjens, Ivonne M C M


    Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems withinan alternative testing strategy to detect the developmental toxicity ofthyroid-active compounds. Model compounds tested included triiodothyronine (T3), propylthiouracil (PTU), methimazole (MMI), sodium perchlorate (NaClO4) and amiodarone hydrochloride (AMI), selected to represent different modes of action affecting thyroid activity. Tested time windows included 48-120 hours post fertilization (hpf), 0-72 hpf and 0-120 hpf. All tested compounds resulted in developmental changes, with T3 being the most potent. The developmental parameters affected included reflective iridophores, beat and glide swimming, inflated swim bladders, as well as resorbed yolk sacs. These effects are only evident by 120 hpf and therefore an existing General Morphology Score (GMS) system was extended to create a General Developmental Score(GDS) that extends beyond the 72 hpfscoring limit of GMS and includes additional parameters that are affected by exposure to model thyroid-active compounds. Moreover, the GDS is cumulative as it includes not only the scoring of developmental morphologies but also integrates developmental dysmorphologies. Exposures from 48-120 hpf did not provide additional information to exposures from 0-120 hpf. The results indicate that the zebrafish GDS can detect the developmental toxicity of thyroid toxicants and may be of use in an integrated testing strategy to reduce, refine and in certain cases replace animal testing.

  3. Using Delaunay triangulation and Voronoi tessellation to predict the toxicities of binary mixtures containing hormetic compound. (United States)

    Qu, Rui; Liu, Shu-Shen; Zheng, Qiao-Feng; Li, Tong


    Concentration addition (CA) was proposed as a reasonable default approach for the ecological risk assessment of chemical mixtures. However, CA cannot predict the toxicity of mixture at some effect zones if not all components have definite effective concentrations at the given effect, such as some compounds induce hormesis. In this paper, we developed a new method for the toxicity prediction of various types of binary mixtures, an interpolation method based on the Delaunay triangulation (DT) and Voronoi tessellation (VT) as well as the training set of direct equipartition ray design (EquRay) mixtures, simply IDVequ. At first, the EquRay was employed to design the basic concentration compositions of five binary mixture rays. The toxic effects of single components and mixture rays at different times and various concentrations were determined by the time-dependent microplate toxicity analysis. Secondly, the concentration-toxicity data of the pure components and various mixture rays were acted as a training set. The DT triangles and VT polygons were constructed by various vertices of concentrations in the training set. The toxicities of unknown mixtures were predicted by the linear interpolation and natural neighbor interpolation of vertices. The IDVequ successfully predicted the toxicities of various types of binary mixtures.

  4. Screening of drugs and toxic compounds with liquid chromatography-linear ion trap tandem mass spectrometry. (United States)

    Sauvage, François-Ludovic; Saint-Marcoux, Franck; Duretz, Bénédicte; Deporte, Didier; Lachatre, Gérard; Marquet, Pierre


    In clinical and forensic toxicology, general unknown screening is used to detect and identify exogenous compounds. In this study, we aimed to develop a comprehensive general unknown screening method based on liquid chromatography coupled with a hybrid triple-quadrupole linear ion trap mass spectrometer. After solid-phase extraction, separation was performed using gradient reversed-phase chromatography. The mass spectrometer was operated in the information-dependent acquisition mode, switching between a survey scan acquired in the Enhanced Mass Spectrometry mode with dynamic subtraction of background noise and a dependent scan obtained in the enhanced product ion scan mode. The complete cycle time was 1.36 s. A library of 1000 enhanced product ion-tandem mass spectrometry spectra in positive mode and 250 in negative mode, generated using 3 alternated collision tensions during each scan, was created by injecting pure solutions of drugs and toxic compounds. Comparison with HPLC-diode array detection and gas chromatography-mass spectrometry for the analysis of 36 clinical samples showed that linear ion trap tandem mass spectrometry could identify most of the compounds (94% of the total). Some compounds were detected only by 1 of the other 2 techniques. Specific clinical cases highlighted the advantages and limitations of the method. A unique combination of new operating modes provided by hybrid triple-quadrupole linear ion trap mass spectrometers and new software features allowed development of a comprehensive and efficient method for the general unknown screening of drugs and toxic compounds in blood or urine.

  5. Toxic effects of nine polycyclic aromatic compounds on Enchytraeus crypticus in artificial soil in relation to their properties. (United States)

    Kobetičová, Klára; Simek, Zdeněk; Brezovský, Jan; Hofman, Jakub


    The aim of this study was to compare the toxic effects of selected two- and three-ringed PAHs (naphthalene, phenanthrene, and anthracene) and their N-heterocyclic analogs with one (quinoline, acridine, and phenanthridine) or two (quinoxaline, phenazine, and 1,10-phenanthroline) nitrogen atoms on the survival and reproduction of Enchytraeus crypticus in artificial soil. Toxicity of compounds was recalculated to soil pore-water concentrations using the data of chemical analyses of 0.01 M CaCl(2) extracts of spiked soils. When toxicity was based on molar concentrations in pore water (μmol/L), it significantly increased with increasing K(ow) value. This relationship indicates nonpolar narcosis as the general toxicity mechanism of the tested compounds. In addition, significant correlation between the toxicity of PACs and their ionization potential has been identified by multidimensional QSAR models.

  6. Alternative testing strategies for predicting developmental toxicity of antifungal compound

    NARCIS (Netherlands)

    Li, H.


    Determination of safe human exposure levels of chemicals in toxicological risk assessments largely relies on animal toxicity data. In these toxicity studies, the highest number of animals are used for reproductive and developmental toxicity testing. Because of economic and ethical reasons, there is

  7. Fungal transporters involved in efflux of natural toxic compounds and fungicides

    NARCIS (Netherlands)

    Del Sorbo, G.; Schoonbeek, H.; Waard, de M.A.


    Survival of microorganisms in natural environments is favored by the capacity to produce compounds toxic to competing organisms and the ability to resist the effects of such toxic compounds. Both factors contribute to a competitive advantage of organisms in ecosystems. All organisms have evolved act

  8. Toxic effects on and structure-toxicity relationships of phenylpropanoids, terpenes, and related compounds in Aedes aegypti larvae. (United States)

    Santos, Sandra R L; Silva, Viviane B; Melo, Manuela A; Barbosa, Juliana D F; Santos, Roseli L C; de Sousa, Damião P; Cavalcanti, Sócrates C H


    In the search for toxic compounds against Aedes aegypti L. (Diptera: Culicidae) larvae, a collection of commercially available aromatic and aliphatic diversely substituted compounds were selected and evaluated. p-Cymene exhibited the highest larvicidal potency LC₅₀ = 51 ppm, whereas 1,8-cineole exhibited the lowest activity value LC₅₀ = 1419 ppm. To aid future work on the search for larvicidal compounds, the structure-toxicity relationships of this collection have been evaluated. The presence of lipophilic groups results in an overall increase in potency. In general, the presence of hydroxyl groups resulted in less potent compounds. However, methylation of such hydroxyls led to an overall increase in potency. The most potent compounds showed comparably good larvicidal activity in A. aegypti larvae as other terpenes, which we assume to be the result of the increased lipophilicity.

  9. Triorganotin as a compound with potential reproductive toxicity in mammals

    Directory of Open Access Journals (Sweden)

    V.S. Delgado Filho


    Full Text Available Organotin compounds are typical environmental contaminants and suspected endocrine-disrupting substances, which cause irreversible sexual abnormality in female mollusks, called "imposex". However, little is known about the capability of triorganotin compounds, such as tributyltin and triphenyltin, to cause disorders in the sexual development and reproductive functions of mammals, including humans and rodents. Moreover, these compounds can act as potential competitive inhibitors of aromatase enzyme and other steroidogenic enzymes, affecting the reproductive capacity of male and female mammals. In this review, we discuss the cellular, biochemical, and molecular mechanisms by which triorganotin compounds induce adverse effects in the mammalian reproductive function.

  10. Sorption of toxic organic compounds on waste-water solids: Correlation with fundamental properties

    Energy Technology Data Exchange (ETDEWEB)

    Dobbs, R.A.; Wang, L.; Govind, R.


    Sorption of toxic organic compounds on primary, mixed-liquor, and digested solids from municipal waste-water treatment plants was correlated with octanol/water partition coefficients and with modified Randic indexes. The correlations developed are useful for assessing the role of sorption in the treatment of toxic or hazardous compounds in conventional biological waste-water treatment plants. Correlations developed provide a basis for predicting the concentration of toxic compounds associated with waste-water solids at a given equilibrium concentration in the aqueous phase. Organics in sludge can impact anaerobic digestion, land spreading, incineration and ocean dumping of sludges. Estimates of the concentration of toxics in sludge allows assessment of the impact of toxics on sludge-disposal options.

  11. Acute Neurobehavorial Toxicity of Flame Retardant Replacement Compounds in Zebrafish Larvae (United States)

    As polybrominated diphenyl ethers (PBDEs) are phased out, numerous compounds areemerging as potential replacement flame retardants for use in consumer and electronicproducts. Little is known, however, about the neurobehavioral toxicity of thesereplacements. This study evaluated t...

  12. Plant-associated bacterial degradation of toxic organic compounds in soil.

    LENUS (Irish Health Repository)

    McGuinness, Martina


    A number of toxic synthetic organic compounds can contaminate environmental soil through either local (e.g., industrial) or diffuse (e.g., agricultural) contamination. Increased levels of these toxic organic compounds in the environment have been associated with human health risks including cancer. Plant-associated bacteria, such as endophytic bacteria (non-pathogenic bacteria that occur naturally in plants) and rhizospheric bacteria (bacteria that live on and near the roots of plants), have been shown to contribute to biodegradation of toxic organic compounds in contaminated soil and could have potential for improving phytoremediation. Endophytic and rhizospheric bacterial degradation of toxic organic compounds (either naturally occurring or genetically enhanced) in contaminated soil in the environment could have positive implications for human health worldwide and is the subject of this review.

  13. Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds. (United States)

    Behl, Mamta; Stout, Matthew D; Herbert, Ronald A; Dill, Jeffrey A; Baker, Gregory L; Hayden, Barry K; Roycroft, Joseph H; Bucher, John R; Hooth, Michelle J


    Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure. Published by Elsevier Ireland Ltd.

  14. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    Energy Technology Data Exchange (ETDEWEB)

    Theunissen, P.T., E-mail: [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Robinson, J.F. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Pennings, J.L.A. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Herwijnen, M.H. van [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Kleinjans, J.C.S. [Department of Toxicogenomics, Maastricht University, Maastricht (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Piersma, A.H. [Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Netherlands Toxicogenomics Centre, Maastricht (Netherlands); Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht (Netherlands)


    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  15. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn). (United States)

    Theunissen, P T; Robinson, J F; Pennings, J L A; van Herwijnen, M H; Kleinjans, J C S; Piersma, A H


    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO-BP) were identified after 24h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO-BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO-BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO-BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  16. In vivo evaluation and comparison of developmental toxicity and teratogenicity of perfluoroalkyl compounds using Xenopus embryos. (United States)

    Kim, Miran; Son, Jungeun; Park, Mi Seon; Ji, Yurim; Chae, Soomin; Jun, Changduk; Bae, Jong-Sup; Kwon, Taek Kyu; Choo, Yun-Sik; Yoon, Hosung; Yoon, Duhak; Ryoo, Jaewoong; Kim, Sang-Hyun; Park, Mae-Ja; Lee, Hyun-Shik


    Perfluoroalkyl compounds (PFCs) are environmental toxicants that persistently accumulate in human blood. Their widespread detection and accumulation in the environment raise concerns about whether these chemicals might be developmental toxicants and teratogens in ecosystem. We evaluated and compared the toxicity of PFCs of containing various numbers of carbon atoms (C8-11 carbons) on vertebrate embryogenesis. We assessed the developmental toxicity and teratogenicity of various PFCs. The toxic effects on Xenopus embryos were evaluated using different methods. We measured teratogenic indices (TIs), and investigated the mechanisms underlying developmental toxicity and teratogenicity by measuring the expression of organ-specific biomarkers such as xPTB (liver), Nkx2.5 (heart), and Cyl18 (intestine). All PFCs that we tested were found to be developmental toxicants and teratogens. Their toxic effects were strengthened with increasing length of the fluorinated carbon chain. Furthermore, we produced evidence showing that perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFuDA) are more potent developmental toxicants and teratogens in an animal model compared to the other PFCs we evaluated [perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA)]. In particular, severe defects resulting from PFDA and PFuDA exposure were observed in the liver and heart, respectively, using whole mount in situ hybridization, real-time PCR, pathologic analysis of the heart, and dissection of the liver. Our studies suggest that most PFCs are developmental toxicants and teratogens, however, compounds that have higher numbers of carbons (i.e., PFDA and PFuDA) exert more potent effects.

  17. Detection of toxic compounds in real water samples using a conductometric tyrosinase biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Anh, Tuan Mai [Laboratoire d' Application de la Chimie a l' Environnement, UMR CNRS 5634, Universite Claude Bernard Lyon I, 43 Boulevard du 11 Nov. 1918, 69622 Villeurbanne Cedex (France); International Training Institute for Materials Science (ITIMS), Hanoi University of Technology, 1 Dai Co Viet, Hanoi, Vietnam (Viet Nam); Dzyadevych, Sergei V. [Laboratory of Biomolecular Electronics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., Kiev 03143 (Ukraine); Prieur, Nicolas [Institute of Natural Products Chemistry, Vietnam National Centre for Science and Technology, Hoang Quoc Viet Str., Hanoi, Vietnam (Viet Nam); Duc, Chien Nguyen [International Training Institute for Materials Science (ITIMS), Hanoi University of Technology, 1 Dai Co Viet, Hanoi, Vietnam (Viet Nam); Pham, T.D. [International Training Institute for Materials Science (ITIMS), Hanoi University of Technology, 1 Dai Co Viet, Hanoi, Vietnam (Viet Nam); Renault, Nicole Jaffrezic [Ecole Centrale de Lyon, CEGELY, UMR CNRS 5005, 36 Avenue Guy de Collongue, 69134 Ecully Cedex (France); Chovelon, Jean-Marc [Laboratoire d' Application de la Chimie a l' Environnement, UMR CNRS 5634, Universite Claude Bernard Lyon I, 43 Boulevard du 11 Nov. 1918, 69622 Villeurbanne Cedex (France)]. E-mail:


    A conductometric tyrosinase biosensor for the detection of some toxic compounds including diuron, atrazine, and copper ions was developed. The work of this biosensor is based on the principle of change of conductivity of the enzyme membrane when tyrosinase either interacts with 4-chlorophenol substrate or is inhibited by pollutants. The different samples tested were solutions containing diuron, atrazine, copper, lead and zinc ions, mixtures of copper/atrazine or copper/diuron and real water samples coming from a Vietnamese river. In the last case, classical techniques such as GC-MS or atomic absorption spectrometry were used in order to estimate exact concentration of these species in real water samples. Results have shown that such a biosensor could be used as an early warning system for the detection of these pollutants, as no matrix effect coming from the real sample was observed and no synergetic or antagonist effects were found for the mixture of toxic compounds. In addition, results were coherent with the content of the tyrosinase inhibitors.

  18. Screening of Compounds Toxicity against Human Monocytic cell line-THP-1 by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Pick Neora


    Full Text Available The worldwide rapid increase in bacterial resistance to numerous antibiotics requires on-going development of new drugs to enter the market. As the development of new antibiotics is lengthy and costly, early monitoring of compound's toxicity is essential in the development of novel agents. Our interest is in a rapid, simple, high throughput screening method to assess cytotoxicity induced by potential agents. Some intracellular pathogens, such as Mycobacterium tuberculosis primary site of infection is human alveolar macrophages. Thus, evaluation of candidate drugs for macrophage toxicity is crucial. Protocols for high throughput drug toxicity screening of macrophages using flow cytometry are lacking in the literature. For this application we modified a preexisting technique, propidium iodide (PI exclusion staining and utilized it for rapid toxicity tests. Samples were prepared in 96 well plates and analyzed by flow cytometry, which allowed for rapid, inexpensive and precise assessment of compound's toxicity associated with cell death.

  19. Selected streambed sediment compounds and water toxicity results for Westside Creeks, San Antonio, Texas, 2014 (United States)

    Crow, Cassi L.; Wilson, Jennifer T.; Kunz, James L.


    IntroductionThe Alazán, Apache, Martínez, and San Pedro Creeks in San Antonio, Texas, are part of a network of urban tributaries to the San Antonio River, known locally as the Westside Creeks. The Westside Creeks flow through some of the oldest neighborhoods in San Antonio. The disruption of streambed sediment is anticipated during a planned restoration to improve and restore the environmental condition of 14 miles of channelized sections of the Westside Creeks in San Antonio. These construction activities can create the potential to reintroduce chemicals found in the sediments into the ecosystem where, depending on hydrologic and environmental conditions, they could become bioavailable and toxic to aquatic life. Elevated concentrations of sediment-associated contaminants often are measured in urban areas such as San Antonio, Tex. Contaminants found in sediment can affect the health of aquatic organisms that ingest sediment. The gradual accumulation of trace elements and organic compounds in aquatic organisms can cause various physiological issues and can ultimately result in death of the aquatic organisms; in addition, subsequent ingestion of aquatic organisms can transfer the accumulated contaminants upward through the food chain (a process called biomagnification).The U.S. Geological Survey, in cooperation with the San Antonio River Authority, collected sediment samples and water samples for toxicity testing from sites on the Westside Creeks as part of an initial characterization of selected contaminants in the study area. Samples were collected in January 2014 during base-flow conditions and again in May 2104 after a period of stormwater runoff (poststorm conditions). Sediment samples were analyzed for selected constituents, including trace elements and organic contaminants such as pesticides, brominated flame retardants, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). In addition, as an indicator of ecological health (and

  20. Determination of Monod kinetics of toxic compounds by respirometry for structure-biodegradability relationships

    Energy Technology Data Exchange (ETDEWEB)

    Govind, R.; Desai, S.; Tabak, H.H.


    The key to the evaluation of the fate of toxic organic chemicals in the environment is dependant on evaluating their susceptibility to biodegradation. Biodegradation is one of the most important mechanisms in controlling the concentration of chemicals in an aquatic system because toxic pollutants can be mineralized and rendered harmless. Experiments using an electrolytic respirometer have been conducted to collect oxygen consumption data of toxic compounds from the list of RCRA and RCRA land banned chemicals (phenols and phthalates). The estimation of Monod kinetic parameters were obtained for all the compounds by a graphical method. The first order kinetic constants for the substituted phenols were related to the structure of the compounds by the group contribution method.

  1. Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

    Directory of Open Access Journals (Sweden)

    Magbubah Essack


    Full Text Available 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.

  2. Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

    KAUST Repository

    Essack, Magbubah


    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.

  3. Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry (United States)

    Essack, Magbubah; Alzubaidy, Hanin S.; Bajic, Vladimir B.; Archer, John A. C.


    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

  4. Environmental impact by toxic compounds from waste treatment; Miljoepaaverkan fraan toxiska aemnen vid hantering av avfall

    Energy Technology Data Exchange (ETDEWEB)

    Loefblad, Gun; Bisaillon, Mattias; Sundberg, Johan (Profu AB (Sweden))


    The study deals with emissions of toxic compounds from waste treatment to the environment with the aim of improving the state of knowledge and to find a way of describing the environmental impact from these substances. Toxicity is one of a number of environmental aspects necessary to address in the planning of waste treatment and in the daily waste treatment routines in order to fulfill the environmental objective A Non-Toxic Environment and other environmental requirements. The study includes waste to incineration, composting and anaerobic digestion. A comparison between methods were made for biological household waste. According to our study, the compounds of importance for waste treatment are metals and persistent organic compounds. These tend to bioaccumulate and enrich in food chains. The substances are important for the environmental objective A Non-Toxic Environment. In a first step the compounds chosen in this study may be suggested for describing toxicity from waste treatment: As, Cd, Cu, Hg, Pb, dioxin, PCB, the phthalate DEHP and the brominated flame retardant HBCDD. Other substances may be added to the list in a next step from up-dated and quality-assured characterisation factors or from other requirements or preferences. There is a limited knowledge on toxic compounds in waste flows and in different environmental compartments. More data are available for metals than for organic substances. There is also a limited knowledge on the fate of the compounds during the waste treatment processes. Most information is found for incineration. During composting and anaerobic digestion the metals will mainly be emitted to the environment by use of the compost and the anaerobic digestion residue. Organic substances will to some extent be degraded during the processes. However, there are gaps of knowledge to fill for the further work on estimating toxic emissions. There is mainly a need for more extensive data on toxic compounds in waste and their variations. A test

  5. Toxicity of Five Phenolic Compounds to Brine Shrimp Artemia sinica(Crustacea:Artemiidae)

    Institute of Scientific and Technical Information of China (English)

    Ali Shaukat; LIU Guangxing; LI Zhengyan; XU Donghui; HUANG Yousong; CHEN Hongju


    The acute toxicity of five phenolic compounds each to 15 d old Artemia sinica was determined in this study. The brine shrimp A. sinica was hatched from the encysted dry eggs (Bohai Bay Brand) produced by Dongying Ocean Artemia Co., Ltd., China at 27℃± 1℃in pre-filtered (through pores of 0.45 µm in diameter) and autoclaved seawater (salinity 31, pH 7.5-8.0) in a cilindroconical glass beaker (2000 mL in volume) under continuous illumination (provided by a side set 20 W fluorescent lamp) with slight aeration. Ten Artemia individuals from the same batch of the hatched were cultured in 10 mL toxicant solution prepared with seawater (salinity 31, pH 7.5-8.0) at room temperature (about 20℃) to determine 24 h, 48 h and 72 h medium lethal concentration (LC50) of 5 phenolic compounds each. It was found that the toxicity of n-heptylphenol was the highest followed by nonylphenol, t-butylphenol, 2,4-dichlorophenol and bisphenol A in order. The LC50 values of the 5 compounds were calculated with regression analysis. The real concentration (in µg L-1) of 5 phenolic compounds each in toxicant solutions was measured with GC/MS analysis. Significant loss of phenolic compounds caused by either adsorption or desorption was not found. The significant difference of LC50 values was found among the five compounds 3 exposure times each. The range between the highest no-observed-effect concentration (NOEC) and 100%death causing concentration of five phenolic compounds each was determined. The toxicity in term of 24 h LC50 value of n-HP was 9.10 times higher than that of BPA, 1.71 times higher than t-BP, 1.53 times higher than 2,4-DCP and 1.36 times higher than NP, respectively.

  6. Flavoring Compounds Dominate Toxic Aldehyde Production during E-Cigarette Vaping. (United States)

    Khlystov, Andrey; Samburova, Vera


    The growing popularity of electronic cigarettes (e-cigarettes) raises concerns about the possibility of adverse health effects to primary users and people exposed to e-cigarette vapors. E-Cigarettes offer a very wide variety of flavors, which is one of the main factors that attract new, especially young, users. How flavoring compounds in e-cigarette liquids affect the chemical composition and toxicity of e-cigarette vapors is practically unknown. Although e-cigarettes are marketed as safer alternatives to traditional cigarettes, several studies have demonstrated formation of toxic aldehydes in e-cigarette vapors during vaping. So far, aldehyde formation has been attributed to thermal decomposition of the main components of e-cigarette e-liquids (propylene glycol and glycerol), while the role of flavoring compounds has been ignored. In this study, we have measured several toxic aldehydes produced by three popular brands of e-cigarettes with flavored and unflavored e-liquids. We show that, within the tested e-cigarette brands, thermal decomposition of flavoring compounds dominates formation of aldehydes during vaping, producing levels that exceed occupational safety standards. Production of aldehydes was found to be exponentially dependent on concentration of flavoring compounds. These findings stress the need for a further, thorough investigation of the effect of flavoring compounds on the toxicity of e-cigarettes.

  7. Toxicity evaluation of 2-hydroxybiphenyl and other compounds involved in studies of fossil fuels biodesulphurisation. (United States)

    Alves, L; Paixão, S M


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

  8. Structural Characterization and Toxicity Prediction of Some Organic Compounds

    Institute of Scientific and Technical Information of China (English)

    LIAO Li-Mia; LI Jian-Feng; WANG Bi


    A new molecular structural characterization(MSC)method called molecular vertexes correlative index(MVCI)was constructed in this paper.The index was used to describe the structures of 45 compounds and a quantitative structure-activity relationship(QSAR)model of toxicity(–lgEC50)was obtained through multiple linear regression(MLR)and stepwise multiple regression(SMR).The correlation coefficient(R)of the model was 0.912,and the standard deviation(SD)of the model was 0.525.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The Leave-One-Out(LOO)Cross-Validation(CV)correlation coefficient(RCV)was 0.816 and the standard deviation(SDCV)was 0.739,respectively.For the external validation,the correlation coefficient(Rtest)was 0.905 and the standard deviation(SDtest)was 0.520,respectively.The results showed that the index was superior in molecular structural representation.The stability and predictability of the model were good.

  9. Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (Oryzias latipes) embryos (United States)

    Liu, Jie; Wei, Lixin; Jingfeng, Yang; Chernick, Melissa; Hinton, David E.


    This study examined developmental toxicity of different mercury compounds, including some used in traditional medicines. Medaka (Oryzias latipes) embryos were exposed to 0.001–10 µM concentrations of MeHg, HgCl2, α-HgS (Zhu Sha), and β-HgS (Zuotai) from stage 10 (6–7 hpf) to 10 days post fertilization (dpf). Of the forms of mercury in this study, the organic form (MeHg) proved the most toxic followed by inorganic mercury (HgCl2), both producing embryo developmental toxicity. Altered phenotypes included pericardial edema with elongated or tube heart, reduction of eye pigmentation, and failure of swim bladder inflation. Both α-HgS and β-HgS were less toxic than MeHg and HgCl2. Total RNA was extracted from survivors three days after exposure to MeHg (0.1 µM), HgCl2 (1 µM), α-HgS (10 µM), or β-HgS (10 µM) to examine toxicity-related gene expression. MeHg and HgCl2 markedly induced metallothionein (MT) and heme oxygenase-1 (Ho-1), while α-HgS and β-HgS failed to induce either gene. Chemical forms of mercury compounds proved to be a major determinant in their developmental toxicity. PMID:27635309

  10. Developmental toxicity from exposure to various forms of mercury compounds in medaka fish (Oryzias latipes embryos

    Directory of Open Access Journals (Sweden)

    Wu Dong


    Full Text Available This study examined developmental toxicity of different mercury compounds, including some used in traditional medicines. Medaka (Oryzias latipes embryos were exposed to 0.001–10 µM concentrations of MeHg, HgCl2, α-HgS (Zhu Sha, and β-HgS (Zuotai from stage 10 (6–7 hpf to 10 days post fertilization (dpf. Of the forms of mercury in this study, the organic form (MeHg proved the most toxic followed by inorganic mercury (HgCl2, both producing embryo developmental toxicity. Altered phenotypes included pericardial edema with elongated or tube heart, reduction of eye pigmentation, and failure of swim bladder inflation. Both α-HgS and β-HgS were less toxic than MeHg and HgCl2. Total RNA was extracted from survivors three days after exposure to MeHg (0.1 µM, HgCl2 (1 µM, α-HgS (10 µM, or β-HgS (10 µM to examine toxicity-related gene expression. MeHg and HgCl2 markedly induced metallothionein (MT and heme oxygenase-1 (Ho-1, while α-HgS and β-HgS failed to induce either gene. Chemical forms of mercury compounds proved to be a major determinant in their developmental toxicity.

  11. Polybrominated dibenzo-p-dioxins, dibenzofurans, and biphenyls: inclusion in the toxicity equivalency factor concept for dioxin-like compounds. (United States)

    van den Berg, Martin; Denison, Michael S; Birnbaum, Linda S; Devito, Michael J; Fiedler, Heidelore; Falandysz, Jerzy; Rose, Martin; Schrenk, Dieter; Safe, Stephen; Tohyama, Chiharu; Tritscher, Angelika; Tysklind, Mats; Peterson, Richard E


    In 2011, a joint World Health Organization (WHO) and United Nations Environment Programme (UNEP) expert consultation took place, during which the possible inclusion of brominated analogues of the dioxin-like compounds in the WHO Toxicity Equivalency Factor (TEF) scheme was evaluated. The expert panel concluded that polybrominated dibenzo-p-dioxins (PBDDs), dibenzofurans (PBDFs), and some dioxin-like biphenyls (dl-PBBs) may contribute significantly in daily human background exposure to the total dioxin toxic equivalencies (TEQs). These compounds are also commonly found in the aquatic environment. Available data for fish toxicity were evaluated for possible inclusion in the WHO-UNEP TEF scheme (van den Berg et al., 1998). Because of the limited database, it was decided not to derive specific WHO-UNEP TEFs for fish, but for ecotoxicological risk assessment, the use of specific relative effect potencies (REPs) from fish embryo assays is recommended. Based on the limited mammalian REP database for these brominated compounds, it was concluded that sufficient differentiation from the present TEF values of the chlorinated analogues (van den Berg et al., 2006) was not possible. However, the REPs for PBDDs, PBDFs, and non-ortho dl-PBBs in mammals closely follow those of the chlorinated analogues, at least within one order of magnitude. Therefore, the use of similar interim TEF values for brominated and chlorinated congeners for human risk assessment is recommended, pending more detailed information in the future.

  12. In vitro approaches to evaluate toxicity induced by organotin compounds tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) in neuroblastoma cells. (United States)

    Ferreira, Martiña; Blanco, Lucía; Garrido, Alejandro; Vieites, Juan M; Cabado, Ana G


    The toxic effects of the organotin compounds (OTCs) monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) were evaluated in vitro in a neuroblastoma human cell line. Mechanisms of cell death, apoptosis versus necrosis, were studied by using several markers: inhibition of cell viability and proliferation, F-actin, and mitochondrial membrane potential changes as well as reactive oxygen species (ROS) production and DNA fragmentation. The most toxic effects were detected with DBT and TBT even at very low concentrations (0.1-1 μM). In contrast, MBT induced lighter cytotoxic changes at the higher doses tested. None of the studied compounds stimulated propidium iodide uptake, although the most toxic chemical, TBT, caused lactate dehydrogenase release at the higher concentrations tested. These findings suggest that in neuroblastoma, OTC-induced cytotoxicity involves different pathways depending on the compound, concentration, and incubation time. A screening method for DBT and TBT quantification based on cell viability loss was developed, allowing a fast detection alternative to complex methodology.

  13. Toxicity evaluation of chlorinated organic compounds using immortalized rat hepatocytes; Fushika rat kansaibo wo mochiita yuki enso kagobutsu no dokusei hyoka no kokoromi

    Energy Technology Data Exchange (ETDEWEB)

    Sone, H.; Nakajima, M.; Yonemoto, J. [National Institute for Environmental Studies, Tsukuba (Japan)


    Chlorinated organic compounds has high priority for toxicity screening among environmental hazardous chemicals. In the present study, we used immortalized rat hepatocytes as a liver model in vitro to evaluate the toxicity of nine chlorinated organic compounds. Toxicity of nine chlorinated organic compounds were evaluated to cellular viability of immortalized rat hapatocytes. The potency of the toxicity based on 50% inhibitory concentration (IC50) value was in the following order: triclocalban>triclosan>3,4-dichloroaniline>2,5-diclorophenol> 2,5-dichloroanisole>p-dichlorobenzene> p-chloroaniline>o-dichlorobenzene=tris (2-chloroethyl) phosphate. The rank order of cytotoxic potency of nine chemicals was compared with toxicity information using animals. The rank order of cytotoxic potency did not relative to the order referenced mean lethal dose (LD50) as an index of acute toxicity of rats or mice. However, the rank order of cytotoxic potency relatively correlated non-observed adverse effect level (NOAEL) under the exposure duration adjusted for chronic toxicity in vivo. These data suggests that the origin of testing cell had better to make match target organ of toxic chemicals for extrapolation from data of bioassay in vitro to in vivo. 16 refs., 2 figs., 3 tabs.

  14. NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis. (United States)

    Lienemann, Kai; Plötz, Thomas; Pestel, Sabine


    The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

  15. Cellular uptake, subcellular distribution and toxicity of arsenic compounds in methylating and non-methylating cells. (United States)

    Dopp, E; von Recklinghausen, U; Diaz-Bone, R; Hirner, A V; Rettenmeier, A W


    , distribution and toxicity of arsenic compounds in methylating and non-methylating cells. 2009 Elsevier Inc. All rights reserved.

  16. Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92

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    William R. Schwan


    Full Text Available Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC50 (125 μg/mL in vitro against several mammalian cell lines, and mice injected intraperiteonally at the highest dose did not exhibit gross toxicity (e.g., altered gait, ungroomed, significant weight loss. Single dose (100 μg/g pharmacokinetic (PK analysis with formulated SK-03-92 showed that peak plasma concentration (1.64 μg/mL was achieved at 20–30 min. Oral relative bioavailability was 8%, and the drug half-life was 20–30 min, demonstrating that SK-03-92 is likely not a candidate for oral delivery. Five-day and two-week PK analyses demonstrated that SK-03-92 plasma levels were low. Multi-dose analysis showed no gross adverse effects to the mice and a SK-03-92 peak plasma concentration of 2.12 μg/mL with the presence of significant concentrations of breakdown products 15 min after dosing. SK-03-92 appeared to be very safe based on tissue culture and mouse gross toxicity determinations, but the peak plasma concentration suggests that a pro-drug of SK-03-92 or preparation of analogs of SK-03-92 with greater bioavailability and longer half-lives are warranted.

  17. Speciation in Metal Toxicity and Metal-Based Therapeutics

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    Douglas M. Templeton


    Full Text Available Metallic elements, ions and compounds produce varying degrees of toxicity in organisms with which they come into contact. Metal speciation is critical to understanding these adverse effects; the adjectives “heavy” and “toxic” are not helpful in describing the biological properties of individual elements, but detailed chemical structures are. As a broad generalization, the metallic form of an element is inert, and the ionic salts are the species that show more significant bioavailability. Yet the salts and other chelates of a metal ion can give rise to quite different toxicities, as exemplified by a range of carcinogenic potential for various nickel species. Another important distinction comes when a metallic element is organified, increasing its lipophilicity and hence its ability to penetrate the blood brain barrier, as is seen, for example, with organic mercury and tin species. Some metallic elements, such as gold and platinum, are themselves useful therapeutic agents in some forms, while other species of the same element can be toxic, thus focusing attention on species interconversions in evaluating metal-based drugs. The therapeutic use of metal-chelating agents introduces new species of the target metal in vivo, and this can affect not only its desired detoxification, but also introduce a potential for further mechanisms of toxicity. Examples of therapeutic iron chelator species are discussed in this context, as well as the more recent aspects of development of chelation therapy for uranium exposure.

  18. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048. (United States)

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo


    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties.

  19. Non-clinical toxicity studies on bioactive compounds within the framework of nutritional and health claims. (United States)

    Gil, Ana Gloria; Arbillaga, Leire; López de Cerain, Adela


    The growing presence of products on the market with added value in terms of health makes essential their regulation and harmonization in critical aspects such as safety. The toxicology applied to the bioactive compounds should demonstrate the absence of toxic effects at doses advised for consumption, as well as evaluate the potential toxic effects in the assumption that the products are used in quantities superior to those recommended. The specific strategy should be defined case by case; therefore, prior to any toxicological development, it is essential to study all the information regarding the bioactive compounds (BACs) characterization, nutridynamics and nutrikinetics, that is available. In this guideline, a general strategy to be applied in the development of BACs is proposed. It includes a first in vitro phase to discard genotoxicity and endocrine effects and a second in vivo phase with different possibilities regarding the duration and the extension of the studies.

  20. Gustatory Receptors Required for Avoiding the Toxic Compound Coumarin in Drosophila melanogaster. (United States)

    Poudel, Seeta; Lee, Youngseok


    Coumarin is a phenolic compound that mainly affects the liver due to its metabolization into a toxic compound. The deterrent and ovicidal activities of coumarin in insect models such as Drosophila melanogaster have been reported. Here we explore the molecular mechanisms by which these insects protect themselves and their eggs from this toxic plant metabolite. Coumarin was fatal to the flies in a dosage-dependent manner. However, coumarin feeding could be inhibited through activation of the aversive gustatory receptor neurons (GRNs), but not the olfactory receptor neurons. Furthermore, three gustatory receptors, GR33a, GR66a, and GR93a, functioned together in coumarin detection by the proboscis. However, GR33a, but not GR66a and GR93a, was required to avoid coumarin during oviposition, with a choice of the same substrates provided as in binary food choice assay. Taken together, these findings suggest that anti-feeding activity and oviposition to avoid coumarin occur via separate mechanisms.

  1. Toxicity of selected tremorgenic mycotoxins and related compounds to Spodoptera frugiperda and Heliothis zea. (United States)

    Dowd, P F; Cole, R J; Vesonder, R F


    A series of tremorgenic mycotoxins and related compounds were tested for oral toxicity to the fall armyworm (Spodoptera frugiperda) and corn earworm (Heliothis zea) by incorporation of materials into artificial diets and examining mortality and weights after 7 days. Significant mortality to both insect species was caused with dihydroxyaflavinine and roseotoxin B, while significant mortality to H. zea was also caused by penitrem A at 25 ppm. After 7 days, weighs of larvae treated with 25 ppm penitrem A, roseotoxin B, and verruculogen were less than 50% of controls for both insect species. Weights of H. zea larvae treated with 25 ppb of penitrem A were less than 50% those of control larvae. Relative toxicities of the tremorgens and related compounds to insects compared to vertebrates are discussed.

  2. Automated high-content assay for compounds selectively toxic to Trypanosoma cruzi in a myoblastic cell line.

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    Julio Alonso-Padilla


    Full Text Available Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, represents a very important public health problem in Latin America where it is endemic. Although mostly asymptomatic at its initial stage, after the disease becomes chronic, about a third of the infected patients progress to a potentially fatal outcome due to severe damage of heart and gut tissues. There is an urgent need for new drugs against Chagas disease since there are only two drugs available, benznidazole and nifurtimox, and both show toxic side effects and variable efficacy against the chronic stage of the disease.Genetically engineered parasitic strains are used for high throughput screening (HTS of large chemical collections in the search for new anti-parasitic compounds. These assays, although successful, are limited to reporter transgenic parasites and do not cover the wide T. cruzi genetic background. With the aim to contribute to the early drug discovery process against Chagas disease we have developed an automated image-based 384-well plate HTS assay for T. cruzi amastigote replication in a rat myoblast host cell line. An image analysis script was designed to inform on three outputs: total number of host cells, ratio of T. cruzi amastigotes per cell and percentage of infected cells, which respectively provides one host cell toxicity and two T. cruzi toxicity readouts. The assay was statistically robust (Z´ values >0.6 and was validated against a series of known anti-trypanosomatid drugs.We have established a highly reproducible, high content HTS assay for screening of chemical compounds against T. cruzi infection of myoblasts that is amenable for use with any T. cruzi strain capable of in vitro infection. Our visual assay informs on both anti-parasitic and host cell toxicity readouts in a single experiment, allowing the direct identification of compounds selectively targeted to the parasite.

  3. Chemopreventive effect of natural dietary compounds on xenobiotic-induced toxicity

    Directory of Open Access Journals (Sweden)

    Jia-Ching Wu


    Full Text Available Contaminants (or pollutants that affect human health have become an important issue, spawning a myriad of studies on how to prevent harmful contaminant-induced effects. Recently, a variety of biological functions of natural dietary compounds derived from consumed foods and plants have been demonstrated in a number of studies. Natural dietary compounds exhibited several beneficial effects for the prevention of disease and the inhibition of chemically-induced carcinogenesis. Contaminant-induced toxicity and carcinogenesis are mostly attributed to the mutagenic activity of reactive metabolites and the disruption of normal biological functions. Therefore, the metabolic regulation of hazardous chemicals is key to reducing contaminant-induced adverse health effects. Moreover, promoting contaminant excretion from the body through Phase I and II metabolizing enzymes is also a useful strategy for reducing contaminant-induced toxicity. This review focuses on summarizing the natural dietary compounds derived from common dietary foods and plants and their possible mechanisms of action in the prevention/suppression of contaminant-induced toxicity.

  4. CORAL: quantitative structure-activity relationship models for estimating toxicity of organic compounds in rats. (United States)

    Toropova, A P; Toropov, A A; Benfenati, E; Gini, G; Leszczynska, D; Leszczynski, J


    For six random splits, one-variable models of rat toxicity (minus decimal logarithm of the 50% lethal dose [pLD50], oral exposure) have been calculated with CORAL software ( The total number of considered compounds is 689. New additional global attributes of the simplified molecular input line entry system (SMILES) have been examined for improvement of the optimal SMILES-based descriptors. These global SMILES attributes are representing the presence of some chemical elements and different kinds of chemical bonds (double, triple, and stereochemical). The "classic" scheme of building up quantitative structure-property/activity relationships and the balance of correlations (BC) with the ideal slopes were compared. For all six random splits, best prediction takes place if the aforementioned BC along with the global SMILES attributes are included in the modeling process. The average statistical characteristics for the external test set are the following: n = 119 ± 6.4, R(2) = 0.7371 ± 0.013, and root mean square error = 0.360 ± 0.037. Copyright © 2011 Wiley Periodicals, Inc.

  5. Mitochondrial diseases caused by toxic compound accumulation: from etiopathology to therapeutic approaches. (United States)

    Di Meo, Ivano; Lamperti, Costanza; Tiranti, Valeria


    Mitochondrial disorders are a group of highly invalidating human conditions for which effective treatment is currently unavailable and characterized by faulty energy supply due to defective oxidative phosphorylation (OXPHOS). Given the complexity of mitochondrial genetics and biochemistry, mitochondrial inherited diseases may present with a vast range of symptoms, organ involvement, severity, age of onset, and outcome. Despite the wide spectrum of clinical signs and biochemical underpinnings of this group of dis-orders, some common traits can be identified, based on both pathogenic mechanisms and potential therapeutic approaches. Here, we will review two peculiar mitochondrial disorders, ethylmalonic encephalopathy (EE) and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), caused by mutations in the ETHE1 and TYMP nuclear genes, respectively. ETHE1 encodes for a mitochondrial enzyme involved in sulfide detoxification and TYMP for a cytosolic enzyme involved in the thymidine/deoxyuridine catabolic pathway. We will discuss these two clinical entities as a paradigm of mitochondrial diseases caused by the accumulation of compounds normally present in traces, which exerts a toxic and inhibitory effect on the OXPHOS system. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  6. The toxicity of the quaternary ammonium compound benzalkonium chloride alone and in mixtures with other anionic compounds to bacteria in test systems with Vibrio fischeri and Pseudomonas putida. (United States)

    Sütterlin, H; Alexy, R; Kümmerer, K


    Mixtures of chemicals are present in the aquatic environment but standard testing methods assess only single compounds. One aspect of this question is the importance of the formation of ionic pairs, for example from quaternary ammonium compounds with organic anions, and the significance of the ionic pairs for bacterial toxicity in the aquatic environment. The aim of the present study was to investigate the toxicity of the cationic quaternary ammonium compound benzalkonium chloride (BAC) against aquatic bacteria in the presence of substances commonly found in wastewater, such as the anionic surfactant linear alkylbenzene sulfonate (LAS), naphthalene sulfonic acid (NSA), sodium dodecylsulfonate (SDS), and benzene sulfonic acid (BSA). The growth inhibition test with Pseudomonas putida and the Vibrio fischeri luminescent inhibition test were used to determine the toxicity of single compounds and compound mixtures. The results found in this study indicate that ion pair formation is of minor significance under the test conditions applied here.

  7. [Assessment of the relationship of properties of chemical compounds and their toxicity to a unified hygienic standardization for chemicals]. (United States)

    Trushkov, V F; Perminov, K A; Sapozhnikova, V V; Ignatova, O L


    The connection of thermodynamic properties and parameters of toxicity of chemical substances was determined. Obtained data are used for the evaluation of toxicity and hygienic rate setting of chemical compounds. The relationship between enthalpy and toxicity of chemical compounds has been established. Orthogonal planning of the experiment was carried out in the course of the investigations. Equation of unified hygienic rate setting in combined, complex, conjunct influence on the organism is presented. Prospects of determination of toxicity and methodology of unified hygienic rate setting in combined, complex, conjunct influence on the organism are presented

  8. Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species of Paenibacillus

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    Saad Musbah Alasil


    Full Text Available The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess the in vitro antibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species of Paenibacillus strain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237, phospholipase A2 inhibitor C21H36O5 (MW 368.512, and an antibacterial agent C14H11N3O2 (MW 253.260. The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groups P>0.05. Overall, our findings suggest that the extract and its purified compounds derived from novel Paenibacillus sp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections.

  9. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels. (United States)

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W; Riebesell, Ulf; Gao, Kunshan


    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  10. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    KAUST Repository

    Jin, Peng


    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  11. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels (United States)

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan


    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  12. Phenolic compounds prevent the oligomerization of α-synuclein and reduce synaptic toxicity. (United States)

    Takahashi, Ryoichi; Ono, Kenjiro; Takamura, Yusaku; Mizuguchi, Mineyuki; Ikeda, Tokuhei; Nishijo, Hisao; Yamada, Masahito


    Lewy bodies, mainly composed of α-synuclein (αS), are pathological hallmarks of Parkinson's disease and dementia with Lewy bodies. Epidemiological studies showed that green tea consumption or habitual intake of phenolic compounds reduced Parkinson's disease risk. We previously reported that phenolic compounds inhibited αS fibrillation and destabilized preformed αS fibrils. Cumulative evidence suggests that low-order αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies. To develop disease modifying therapies for α-synucleinopathies, we examined effects of phenolic compounds (myricetin (Myr), curcumin, rosmarinic acid (RA), nordihydroguaiaretic acid, and ferulic acid) on αS oligomerization. Using methods such as photo-induced cross-linking of unmodified proteins, circular dichroism spectroscopy, the electron microscope, and the atomic force microscope, we showed that Myr and RA inhibited αS oligomerization and secondary structure conversion. The nuclear magnetic resonance analysis revealed that Myr directly bound to the N-terminal region of αS, whereas direct binding of RA to monomeric αS was not detected. Electrophysiological assays for long-term potentiation in mouse hippocampal slices revealed that Myr and RA ameliorated αS synaptic toxicity by inhibition of αS oligomerization. These results suggest that Myr and RA prevent the αS aggregation process, reducing the neurotoxicity of αS oligomers. To develop disease modifying therapies for α-synucleinopathies, we examined effects of phenolic compounds on α-synuclein (αS) oligomerization. Phenolic compounds, especially Myricetin (Myr) and Rosmarinic acid (RA), inhibited αS oligomerization and secondary structure conversion. Myr and RA ameliorated αS synaptic toxicity on the experiment of long-term potentiation. Our results suggest that Myr and RA prevent αS aggregation process and reduce the neurotoxicity of αS oligomers. Phenolic compounds are good

  13. Toxicity of Rhododendron anthopogonoides Essential Oil and Its Constituent Compounds towards Sitophilus zeamais

    Directory of Open Access Journals (Sweden)

    Qi Zhi Liu


    Full Text Available The screening of several Chinese medicinal plants for insecticidal principles showed that essential oil of Rhododendron anthopogonoides flowering aerial parts possessed significant toxicity against maize weevils, Sitophilus zeamais. A total of 37 components were identified in the essential oil and the main constituents of the essential oil were 4-phenyl-2-butanone (27.22%, nerolidol (8.08%, 1,4-cineole (7.85%, caryophyllene (7.63% and γ-elemene (6.10%, followed by α-farnesene (4.40% and spathulenol (4.19%. Repeated bioactivity-directed chromatographic separation on silica gel columns led us to isolate three compounds, namely 4-phenyl-2-butanone, 1,4-cineole, and nerolidol. 4-Phenyl-2-butanone shows pronounced contact toxicity against S. zeamais (LD50 = 6.98 mg/adult and was more toxic than either 1,4-cineole or nerolidol (LD50 = 50.86 mg/adult and 29.30 mg/adult, respectively against the maize weevils, while the crude essential oil had a LD50 value of 11.67 mg/adult. 4-Phenyl-2-butanone and 1,4-cineole also possessed strong fumigant toxicity against the adults of S. zeamais (LC50 = 3.80 mg/L and 21.43 mg/L while the crude essential oil had a LC50 value of 9.66 mg/L.

  14. Toxic volatile organic compounds in environmental tobacco smoke: Emission factors for modeling exposures of California populations

    Energy Technology Data Exchange (ETDEWEB)

    Daisey, J.M.; Mahanama, K.R.R.; Hodgson, A.T. [Lawrence Berkeley Lab., CA (United States)


    The primary objective of this study was to measure emission factors for selected toxic air contaminants in environmental tobacco smoke (ETS) using a room-sized environmental chamber. The emissions of 23 volatile organic compounds (VOCs), including, 1,3-butadiene, three aldehydes and two vapor-phase N-nitrosamines were determined for six commercial brands of cigarettes and reference cigarette 1R4F. The commercial brands were selected to represent 62.5% of the cigarettes smoked in California. For each brand, three cigarettes were machine smoked in the chamber. The experiments were conducted over four hours to investigate the effects of aging. Emission factors of the target compounds were also determined for sidestream smoke (SS). For almost all target compounds, the ETS emission factors were significantly higher than the corresponding SS values probably due to less favorable combustion conditions and wall losses in the SS apparatus. Where valid comparisons could be made, the ETS emission factors were generally in good agreement with the literature. Therefore, the ETS emission factors, rather than the SS values, are recommended for use in models to estimate population exposures from this source. The variabilities in the emission factors ({mu}g/cigarette) of the selected toxic air contaminants among brands, expressed as coefficients of variation, were 16 to 29%. Therefore, emissions among brands were Generally similar. Differences among brands were related to the smoked lengths of the cigarettes and the masses of consumed tobacco. Mentholation and whether a cigarette was classified as light or regular did not significantly affect emissions. Aging was determined not to be a significant factor for the target compounds. There were, however, deposition losses of the less volatile compounds to chamber surfaces.

  15. The effect of treatment stages on the coking wastewater hazardous compounds and their toxicity. (United States)

    Wei, Xiao-xue; Zhang, Zi-yang; Fan, Qing-lan; Yuan, Xiao-ying; Guo, Dong-sheng


    This study investigated the change of hazardous materials in coking wastewater at different treatment stages (anaerobic, anaerobic/aerobic, anaerobic/aerobic/photo degradation, anaerobic/aerobic/ozone oxidation treatment) and the effects of them on the development of maize embryos and the activity of amylase and protease in maize seeds. Moreover the interaction of refractory organic matters in the wastewater at different treatment stages with amylase and protease also were determined in vitro. The results show that the biodegradable and the refractory organic compounds in the wastewater both can affect maize embryo development (germination inhibition rate is 19.3% for biodegradable organic compounds). As the treatment stage preceding, the inhibition effect of coking wastewater on the development of the maize embryo (for germination inhibition rates change from 49.3% to 24.6%) and on enzymatic activity (inhibition rates change from 63.9% to 22.4% for amylase) decreases gradually, but the photo-degradation treatment to anaerobic/aerobic effluent can increase its toxicity. The changes in the ability of the refractory organic compounds to bind with enzyme proteins, combined with the analysis of the organic components by GC/MS, show that in the process of coking wastewater treatment no new toxic chemicals were produced.

  16. Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds. (United States)

    Selderslaghs, Ingrid W T; Blust, Ronny; Witters, Hilda E


    To anticipate to increased testing needs for reproductive toxicity and 3R approaches, we studied zebrafish embryo/larva as an alternative for animal testing for developmental toxicity and embryotoxicity and evaluated a training set of 27 compounds with a standardized protocol. The classification of compounds in the zebrafish embryo/larva assay, based on a prediction model using a TI (teratogenic index) cut-off value of 2, was compared to available animal and human data. When comparing the classification of compounds in the zebrafish embryo/larva assay to available animal classification, a sensitivity of 72% and specificity of 100% were obtained. The predictive values obtained in comparison to a limited set of human data were 50, 60% respectively for teratogens, non-teratogens. Overall, we demonstrated that the zebrafish embryo/larva assay, may be used as screening tool for prioritization of compounds and could contribute to reduction of animal experiments in the field of developmental toxicology.

  17. Facility monitoring of toxic industrial compounds in air using an automated, fieldable, miniature mass spectrometer. (United States)

    Smith, Jonell N; Keil, Adam; Likens, Jane; Noll, Robert J; Cooks, R Graham


    Gaseous samples of nine toxic industrial compounds (acrolein, acrylonitrile, carbon disulfide, cyanogen chloride, ethylene oxide, formaldehyde, hydrogen cyanide, phosgene, and sulfur dioxide) were detected, identified, and quantitated using a fully automated, fieldable, miniature mass spectrometer equipped with a glow discharge electron ionization source and a cylindrical ion trap mass analyzer. The instrument was outfitted with a combined direct air leak and dual thermal desorption tube inlet that allowed for continuous sampling of compounds with throughput times of 2 min or less. Most compounds showed a linear response over the concentration ranges studied (sub-parts per billion [ppb] to parts per million [ppm]). Sorbent tube limits of detection (20 ppb to 8 ppm for all analytes) were lower than those reported for the two compounds examined using direct leak (acrylonitrile 16 ppm and phosgene 500 ppb). All limits of detection were below the concentration at which the compound poses an immediate danger to life and health. Sensitivity, probability of true positives, and the false positive rate for each analyte were investigated and described using receiver operating characteristic (ROC) curves. High quality data with low false positive and negative rates are indicative of the good chemical specificity and sensitivity of the instrument. Complex matrices consisting of second-hand smoke, gasoline exhaust, diesel fuel exhaust, and multiple analytes were also studied. Detection limits for analytes generally increased in the mixtures, but analytes were still detected at concentrations as low as 100 ppb.

  18. Modeling the toxicity of aromatic compounds to tetrahymena pyriformis: the response surface methodology with nonlinear methods. (United States)

    Ren, Shijin


    Response surface models based on multiple linear regression had previously been developed for the toxicity of aromatic chemicals to Tetrahymena pyriformis. However, a nonlinear relationship between toxicity and one of the molecular descriptors in the response surface model was observed. In this study, response surface models were established using six nonlinear modeling methods to handle the nonlinearity exhibited in the aromatic chemicals data set. All models were validated using the method of cross-validation, and prediction accuracy was tested on an external data set. Results showed that response surface models based on locally weighted regression scatter plot smoothing (LOESS), multivariate adaptive regression splines (MARS), neural networks (NN), and projection pursuit regression (PPR) provided satisfactory power of model fitting and prediction and had similar applicabilities. The response surface models based on nonlinear methods were difficult to interpret and conservative in discriminating toxicity mechanisms.

  19. Acaricidal activity of eugenol based compounds against scabies mites.

    Directory of Open Access Journals (Sweden)

    Cielo Pasay

    Full Text Available BACKGROUND: Human scabies is a debilitating skin disease caused by the "itch mite" Sarcoptes scabiei. Ordinary scabies is commonly treated with topical creams such as permethrin, while crusted scabies is treated with topical creams in combination with oral ivermectin. Recent reports of acaricide tolerance in scabies endemic communities in Northern Australia have prompted efforts to better understand resistance mechanisms and to identify potential new acaricides. In this study, we screened three essential oils and four pure compounds based on eugenol for acaricidal properties. METHODOLOGY/PRINCIPAL FINDINGS: Contact bioassays were performed using live permethrin-sensitive S. scabiei var suis mites harvested from pigs and permethrin-resistant S. scabiei var canis mites harvested from rabbits. Results of bioassays showed that clove oil was highly toxic against scabies mites. Nutmeg oil had moderate toxicity and ylang ylang oil was the least toxic. Eugenol, a major component of clove oil and its analogues--acetyleugenol and isoeugenol, demonstrated levels of toxicity comparable to benzyl benzoate, the positive control acaricide, killing mites within an hour of contact. CONCLUSIONS: The acaricidal properties demonstrated by eugenol and its analogues show promise as leads for future development of alternative topical acaricides to treat scabies.

  20. Read-Across Prediction of the Acute Toxicity of Organic Compounds toward the Water Flea Daphnia magna. (United States)

    Kühne, Ralph; Ebert, Ralf-Uwe; von der Ohe, Peter C; Ulrich, Nadin; Brack, Werner; Schüürmann, Gerrit


    According to the European REACH Directive, the acute daphnid toxicity needs to be assessed for industrial chemicals with market volumes ≥1 t/a. Employing a data set of 1365 organic compounds with experimental 48-h LC50 data for Daphnia magna, a read-across approach has been developed that makes use of the atom-centered fragment (ACF) method as quantitative measure for structural similarity. Both quantitative log LC50 predictions and a discrimination between narcosis-level and excess toxicity can be obtained, augmented by similarity-triggered information that characterizes a compound as inside or outside the quantitative or qualitative model domain. Reading across proceeds as interpolation of the toxicity enhancement (Te ) over predicted narcosis-level toxicity, taking experimental log Te values from similarity-selected reference compounds as input. The resultant decision tree model yields r(2) =0.85 and rms=0.66 for the subset of 757 compounds (56 %) identified as inside the quantitative model domain, and can handle further 318 compounds (23 %) with the categorical submodel, with 290 compounds (21 %) being outside its domain. The new in silico approach appears useful as ITS (Integrated Testing Strategy) tool for the daphnid toxicity assessment. The discussion includes a comparison of Kow - and LSER-predicted narcosis-level toxicity in the read-across context. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Developmental toxicity of TCDD and related compounds: Species sensitivities and differences

    Energy Technology Data Exchange (ETDEWEB)

    Birnbaum, L.S.


    The issue of the developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds has been the subject of two recent reviews (Morrissey and Schwetz, 1989; Couture et al., 1990a). There is little doubt that TCDD is one of the most potent developmental toxins known, yet its production of frank structural malformations in species other than in the mouse are poorly described. The objective of the review is to critically address the role which TCDD and its approximate isostereomers have in causing a wide array of developmental effects in various species, including some very recent results. The bias of the author is that the teratogenic response of the mouse is a reflection of extreme sensitivity of the species to the induction of frank teratogenic responses in two epithelial tissues. That is, that the mouse is an outlier in the field of developmental toxicity, possibly in parallel to the exquisite sensitivity of the guinea pig vs the resistance of the hamster to the lethal effects of TCDD, or in the resistance of haired rodents to the induction of chloracne. The crucial point is that most species respond similarly to TCDD; for any given endpoint outliers will exist. However, no species is an outlier for all responses. In terms of developmental toxicity, essentially all species critically examined to date demonstrate potent developmentally toxic effects following exposure to TCDD and related chemicals. Relatively low doses to the dam (varying within an order of magnitude) result in embryo/fetal toxicity. The actual induction of terata is an extremely rare response. (Copyright (c) 1991 Cold Spring Harbor Laboratory Press.)

  2. Monte Carlo method for predicting of cardiac toxicity: hERG blocker compounds. (United States)

    Gobbi, Marco; Beeg, Marten; Toropova, Mariya A; Toropov, Andrey A; Salmona, Mario


    The estimation of the cardiotoxicity of compounds is an important task for the drug discovery as well as for the risk assessment in ecological aspect. The experimental estimation of the above endpoint is complex and expensive. Hence, the theoretical computational methods are very attractive alternative of the direct experiment. A model for cardiac toxicity of 400 hERG blocker compounds (pIC50) is built up using the Monte Carlo method. Three different splits into the visible training set (in fact, the training set plus the calibration set) and invisible validation sets examined. The predictive potential is very good for all examined splits. The statistical characteristics for the external validation set are (i) the coefficient of determination r(2)=(0.90-0.93); and (ii) root-mean squared error s=(0.30-0.40). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Rigorous selection of random forest models for identifying compounds that activate toxicity-related pathways

    Directory of Open Access Journals (Sweden)

    Yoshihiro eUesawa


    Full Text Available Random forest (RF is a machine-learning ensemble method with high predictive performance. Majority voting in RF uses the discrimination results in numerous decision trees produced from bootstrapping data. For the same dataset, the bootstrapping process yields different predictive capacities in each generation. As participants in the Toxicology in the 21st Century (Tox21 DATA Challenge 2014, we produced numerous RF models for predicting the structures of compounds that can activate each toxicity-related pathway, and then selected the model with the highest predictive ability. Half of the compounds in the training dataset supplied by the competition organizer were allocated to the validation dataset. The remaining compounds were used in model construction. The charged and uncharged forms of each molecule were calculated using the molecular operating environment (MOE software. Subsequently, the descriptors were computed using MOE, MarvinView, and Dragon. These combined methods yielded over 4,071 descriptors for model construction. Using these descriptors, pattern recognition analyses were performed by RF implemented in JMP Pro (a statistical software package. A hundred to two hundred RF models were generated for each pathway. The predictive performance of each model was tested against the validation dataset, and the best-performing model was selected. In the competition, the latter model selected a best-performing model from the 50% test set that best predicted the structures of compounds that activate the estrogen receptor ligand-binding domain (ER-LBD.

  4. Fumigant toxicity of cassia and cinnamon oils and cinnamaldehyde and structurally related compounds to Dermanyssus gallinae (Acari: Dermanyssidae). (United States)

    Na, Young Eun; Kim, Soon-Il; Bang, Hea-Son; Kim, Byung-Seok; Ahn, Young-Joon


    The toxicity of two cassia oils, four cinnamon oils and (E)-cinnamaldehyde and (E)-cinnamic acid and 34 structurally related compounds to adult Dermanyssus gallinae (De Geer) collected from a poultry house was examined using a vapour-phase mortality bioassay. Results were compared with those of dichlorvos, a conventional acaricide. The cassia and cinnamon oils (cinnamon technical, cinnamon #500, cassia especial, cassia true, cinnamon bark and cinnamon green leaf) exhibited good fumigant toxicity (LD(50), 11.79-26.40 μg cm(-3)). α-Methyl-(E)-cinnamaldehyde (LD(50), 0.45 μg cm(-3)) and (E)-cinnamaldehyde (0.54 μg cm(-3)) were the most toxic compounds and the toxicity of these compounds was comparable to that of dichlorvos (0.30 μg cm(-3)). Potent fumigant toxicity was also observed in allyl cinnamate, ethyl-α-cyanocinnamate, (E)-2-methoxylcinnamic acid and (Z)-2-methoxylcinnamic acid (LD(50), 0.81-0.92 μg cm(-3)). Structure-activity relationships indicate that structural characteristics, such as types of functional groups and carbon skeleton rather than vapour pressure parameter, appear to play a role in determining toxicity. The essential oils and compounds described merit further study as potential acaricides for the control of D. gallinae populations as fumigants with contact action due to global efforts to reduce the level of highly toxic synthetic acaricides in the agricultural environment.

  5. Toxicity of naturally occurring Bio-fly and chitosan compounds to control the Mediterranean fruit fly Ceratitis capitata (Wiedemann). (United States)

    Rabea, E I; Nasr, H M; Badawy, M E I; El-Gendy, I R


    The efficacy of five compounds of a biopolymer chitosan and Bio-fly (Beauveria bassiana fungus) as biopesticide was evaluated on Ceratitis capitata under laboratory conditions. The inhibitory effects on acetylcholinesterase (AChE) and adenosinetriphosphatase (ATPase) as biochemical indicators were also determined in vivo. The results indicated that B. bassiana based Bio-fly exhibited significant toxicity against C. capitata (LC50 = 3008 and 3126 mg/L after 48 h in females and males, respectively) followed by the derivatives of chitosan, N-(4-propylbenzyl)chitosan and N-(2-nitrobenzyl)chitosan. Bio-fly displayed remarkable inhibition of AChE activity (IC50 = 2220 mg/L) while N-(2-chloro,6-flourobenzyl)chitosan, N-(4-propylbenzyl)chitosan and N-(3,4-methylenedioxybenzyl) chitosan had no significant difference in inhibitory action. In adult males, N-(2-nitrobenzyl)chitosan exhibited the highest inhibitory action (IC50 = 6569 mg/L). In addition, the toxic effects of the tested compounds on the activity of ATPase indicated that highly significant inhibition was found with N-(4-propylbenzyl)chitosan with an IC50 of 8194 and 8035 mg/L, in females and males, respectively.

  6. Are luminescent bacteria suitable for online detection and monitoring of toxic compounds in drinking water and its sources? (United States)

    Woutersen, Marjolijn; Belkin, Shimshon; Brouwer, Bram; van Wezel, Annemarie P; Heringa, Minne B


    Biosensors based on luminescent bacteria may be valuable tools to monitor the chemical quality and safety of surface and drinking water. In this review, an overview is presented of the recombinant strains available that harbour the bacterial luciferase genes luxCDABE, and which may be used in an online biosensor for water quality monitoring. Many bacterial strains have been described for the detection of a broad range of toxicity parameters, including DNA damage, protein damage, membrane damage, oxidative stress, organic pollutants, and heavy metals. Most lux strains have sensitivities with detection limits ranging from milligrams per litre to micrograms per litre, usually with higher sensitivities in compound-specific strains. Although the sensitivity of lux strains can be enhanced by various molecular manipulations, most reported detection thresholds are still too high to detect levels of individual contaminants as they occur nowadays in European drinking waters. However, lux strains sensing specific toxic effects have the advantage of being able to respond to mixtures of contaminants inducing the same effect, and thus could be used as a sensor for the sum effect, including the effect of compounds that are as yet not identified by chemical analysis. An evaluation of the suitability of lux strains for monitoring surface and drinking water is therefore provided.

  7. New analysis of the toxic compounds from the Androctonus mauretanicus mauretanicus scorpion venom. (United States)

    Oukkache, Naoual; Rosso, Jean-Pierre; Alami, Meriem; Ghalim, Norredine; Saïle, Rachid; Hassar, Mohammed; Bougis, Pierre E; Martin-Eauclaire, Marie-France


    Scorpion venoms are very complex mixtures of molecules, most of which are peptides displaying different kinds of biological activity. Indeed, these peptides specifically bind to a variety of pharmacological targets, in particular ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca2+ and Cl(-) currents have been described in scorpion venoms. In this work, we have used several specific antibodies raised against the most lethal scorpion toxins already described to screen the Moroccan scorpion Androctonus mauretanicus mauretanicus venom in order to characterize new compounds. This immunological screening was also implemented by toxicity tests in mice and with mass spectrometry study, providing new informations on the molecular composition of this venom. In fine, we were able to determine the molecular masses of 70-80 different compounds. According to the immunological data obtained, many toxins cross-react with three sera raised against the most lethal alpha-toxins found in North African scorpion venoms, but not at all with those raised against the main beta-toxins from South and North American venoms. Some of the previously described toxins from Androctonus mauretanicus mauretanicus venom could thus be detected by combining immunological tests, toxicity in mice and molecular masses. Among these toxins, one of them, which showed a mild cross-reaction with the serum raised against AaH I (a highly potent toxin from the venom of Androctonus australis), was identified as Amm III and fully sequenced.

  8. Acute Toxicity of the Antifouling Compound Butenolide in Non-Target Organisms

    KAUST Repository

    Zhang, Yi-Fan


    Butenolide [5-octylfuran-2(5H)-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target) organisms. According to OECD\\'s guideline, the predicted no effect concentration (PNEC) was 0.168 µg l^(−1), which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish) embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK), Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound.

  9. Gustatory Receptors Required for Avoiding the Toxic Compound Coumarin in Drosophila melanogaster (United States)

    Poudel, Seeta; Lee, Youngseok


    Coumarin is a phenolic compound that mainly affects the liver due to its metabolization into a toxic compound. The deterrent and ovicidal activities of coumarin in insect models such as Drosophila melanogaster have been reported. Here we explore the molecular mechanisms by which these insects protect themselves and their eggs from this toxic plant metabolite. Coumarin was fatal to the flies in a dosage-dependent manner. However, coumarin feeding could be inhibited through activation of the aversive gustatory receptor neurons (GRNs), but not the olfactory receptor neurons. Furthermore, three gustatory receptors, GR33a, GR66a, and GR93a, functioned together in coumarin detection by the proboscis. However, GR33a, but not GR66a and GR93a, was required to avoid coumarin during oviposition, with a choice of the same substrates provided as in binary food choice assay. Taken together, these findings suggest that anti-feeding activity and oviposition to avoid coumarin occur via separate mechanisms. PMID:26912085

  10. Acute toxicity of the antifouling compound butenolide in non-target organisms.

    Directory of Open Access Journals (Sweden)

    Yi-Fan Zhang

    Full Text Available Butenolide [5-octylfuran-2(5H-one] is a recently discovered and very promising anti-marine-fouling compound. In this study, the acute toxicity of butenolide was assessed in several non-target organisms, including micro algae, crustaceans, and fish. Results were compared with previously reported results on the effective concentrations used on fouling (target organisms. According to OECD's guideline, the predicted no effect concentration (PNEC was 0.168 µg l(-1, which was among one of the highest in representative new biocides. Mechanistically, the phenotype of butenolide-treated Danio rerio (zebrafish embryos was similar to the phenotype of the pro-caspase-3 over-expression mutant with pericardial edema, small eyes, small brains, and increased numbers of apoptotic cells in the bodies of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the activation of c-Jun N-terminal kinases (JNK, Bcl-2 family proteins, and caspases and proteasomes/lysosomes involved in this process. This is the first detailed toxicity and toxicology study on this antifouling compound.

  11. A gene in the multidrug and toxic compound extrusion (MATE) family confers aluminum tolerance in sorghum. (United States)

    Magalhaes, Jurandir V; Liu, Jiping; Guimarães, Claudia T; Lana, Ubiraci G P; Alves, Vera M C; Wang, Yi-Hong; Schaffert, Robert E; Hoekenga, Owen A; Piñeros, Miguel A; Shaff, Jon E; Klein, Patricia E; Carneiro, Newton P; Coelho, Cintia M; Trick, Harold N; Kochian, Leon V


    Crop yields are significantly reduced by aluminum toxicity on highly acidic soils, which comprise up to 50% of the world's arable land. Candidate aluminum tolerance proteins include organic acid efflux transporters, with the organic acids forming non-toxic complexes with rhizosphere aluminum. In this study, we used positional cloning to identify the gene encoding a member of the multidrug and toxic compound extrusion (MATE) family, an aluminum-activated citrate transporter, as responsible for the major sorghum (Sorghum bicolor) aluminum tolerance locus, Alt(SB). Polymorphisms in regulatory regions of Alt(SB) are likely to contribute to large allelic effects, acting to increase Alt(SB) expression in the root apex of tolerant genotypes. Furthermore, aluminum-inducible Alt(SB) expression is associated with induction of aluminum tolerance via enhanced root citrate exudation. These findings will allow us to identify superior Alt(SB) haplotypes that can be incorporated via molecular breeding and biotechnology into acid soil breeding programs, thus helping to increase crop yields in developing countries where acidic soils predominate.

  12. Bioaccumulation and toxicity of selenium compounds in the green alga Scenedesmus quadricauda

    Directory of Open Access Journals (Sweden)

    Doucha Jiří


    Full Text Available Abstract Background Selenium is a trace element performing important biological functions in many organisms including humans. It usually affects organisms in a strictly dosage-dependent manner being essential at low and toxic at higher concentrations. The impact of selenium on mammalian and land plant cells has been quite extensively studied. Information about algal cells is rare despite of the fact that they could produce selenium enriched biomass for biotechnology purposes. Results We studied the impact of selenium compounds on the green chlorococcal alga Scenedesmus quadricauda. Both the dose and chemical forms of Se were critical factors in the cellular response. Se toxicity increased in cultures grown under sulfur deficient conditions. We selected three strains of Scenedesmus quadricauda specifically resistant to high concentrations of inorganic selenium added as selenite (Na2SeO3 – strain SeIV, selenate (Na2SeO4 – strain SeVI or both – strain SeIV+VI. The total amount of Se and selenomethionine in biomass increased with increasing concentration of Se in the culturing media. The selenomethionine made up 30–40% of the total Se in biomass. In both the wild type and Se-resistant strains, the activity of thioredoxin reductase, increased rapidly in the presence of the form of selenium for which the given algal strain was not resistant. Conclusion The selenium effect on the green alga Scenedesmus quadricauda was not only dose dependent, but the chemical form of the element was also crucial. With sulfur deficiency, the selenium toxicity increases, indicating interference of Se with sulfur metabolism. The amount of selenium and SeMet in algal biomass was dependent on both the type of compound and its dose. The activity of thioredoxin reductase was affected by selenium treatment in dose-dependent and toxic-dependent manner. The findings implied that the increase in TR activity in algal cells was a stress response to selenium cytotoxicity

  13. Cerium-iron-based magnetic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Chen; Pinkerton, Frederick E.; Herbst, Jan F.


    New magnetic materials containing cerium, iron, and small additions of a third element are disclosed. These materials comprise compounds Ce(Fe.sub.12-xM.sub.x) where x=1-4, having the ThMn.sub.12 tetragonal crystal structure (space group I4/mmm, #139). Compounds with M=B, Al, Si, P, S, Sc, Co, Ni, Zn, Ga, Ge, Zr, Nb, Hf, Ta, and W are identified theoretically, and one class of compounds based on M=Si has been synthesized. The Si cognates are characterized by large magnetic moments (4.pi.M.sub.s greater than 1.27 Tesla) and high Curie temperatures ( C.). The Ce(Fe.sub.12-xM.sub.x) compound may contain one or more of Ti, V, Cr, and Mo in combination with an M element. Further enhancement in T.sub.c is obtained by nitriding the Ce compounds through heat treatment in N.sub.2 gas while retaining the ThMn.sub.12 tetragonal crystal structure; for example CeFe.sub.10Si.sub.2N.sub.1.29 has C.

  14. Organic waste compounds in streams: Occurrence and aquatic toxicity in different stream compartments, flow regimes, and land uses in southeast Wisconsin, 2006–9 (United States)

    Baldwin, Austin K.; Corsi, Steven R.; Richards, Kevin D.; Geis, Steven W.; Magruder, Christopher


    An assessment of organic chemicals and aquatic toxicity in streams located near Milwaukee, Wisconsin, indicated high potential for adverse impacts on aquatic organisms that could be related to organic waste compounds (OWCs). OWCs used in agriculture, industry, and households make their way into surface waters through runoff, leaking septic-conveyance systems, regulated and unregulated discharges, and combined sewage overflows, among other sources. Many of these compounds are toxic at elevated concentrations and (or) known to have endocrine-disrupting potential, and often they occur as complex mixtures. There is still much to be learned about the chronic exposure effects of these compounds on aquatic populations. During 2006–9, the U.S. Geological Survey, in cooperation with the Milwaukee Metropolitan Sewerage District (MMSD), conducted a study to determine the occurrence and potential toxicity of OWCs in different stream compartments and flow regimes for streams in the Milwaukee area. Samples were collected at 17 sites and analyzed for a suite of 69 OWCs. Three types of stream compartments were represented: water column, streambed pore water, and streambed sediment. Water-column samples were subdivided by flow regime into stormflow and base-flow samples. One or more compounds were detected in all 196 samples collected, and 64 of the 69 compounds were detected at least once. Base-flow samples had the lowest detection rates, with a median of 12 compounds detected per sample. Median detection rates for stormflow, pore-water, and sediment samples were more than double that of base-flow samples. Compounds with the highest detection rates include polycyclic aromatic hydrocarbons (PAHs), insecticides, herbicides, and dyes/pigments. Elevated occurrence and concentrations of some compounds were detected in samples from urban sites, as compared with more rural sites, especially during stormflow conditions. These include the PAHs and the domestic waste

  15. ToxAlerts: a Web server of structural alerts for toxic chemicals and compounds with potential adverse reactions. (United States)

    Sushko, Iurii; Salmina, Elena; Potemkin, Vladimir A; Poda, Gennadiy; Tetko, Igor V


    The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at, and it is constantly

  16. Understanding the toxicological potential of aerosol organic compounds using informatics based screening (United States)

    Topping, David; Decesari, Stefano; Bassan, Arianna; Pavan, Manuela; Ciacci, Andrea


    Exposure to atmospheric particulate matter is responsible for both short-term and long-term adverse health effects. So far, all efforts spent in achieving a systematic epidemiological evidence of specific aerosol compounds determining the overall aerosol toxicity were unsuccessful. The results of the epidemiological studies apparently conflict with the laboratory toxicological analyses which have highlighted very different chemical and toxicological potentials for speciated aerosol compounds. Speciation remains a problem, especially for organic compounds: it is impossible to conduct screening on all possible molecular species. At the same time, research on toxic compounds risks to be biased towards the already known compounds, such as PAHs and dioxins. In this study we present results from an initial assessment of the use of in silico methods (i.e. (Q)SAR, read-across) to predict toxicity of atmospheric organic compounds including evaluation of applicability of a variety of popular tools (e.g. OECD QSAR Toolbox) for selected endpoints (e.g. genotoxicity). Compounds are categorised based on the need of new experimental data for the development of in silico approaches for toxicity prediction covering this specific chemical space, namely the atmospheric aerosols. Whilst only an initial investigation, we present recommendations for continuation of this work.

  17. Environmental feedbacks and engineered nanoparticles: mitigation of silver nanoparticle toxicity to Chlamydomonas reinhardtii by algal-produced organic compounds.

    Directory of Open Access Journals (Sweden)

    Louise M Stevenson

    Full Text Available The vast majority of nanotoxicity studies measures the effect of exposure to a toxicant on an organism and ignores the potentially important effects of the organism on the toxicant. We investigated the effect of citrate-coated silver nanoparticles (AgNPs on populations of the freshwater alga Chlamydomonas reinhardtii at different phases of batch culture growth and show that the AgNPs are most toxic to cultures in the early phases of growth. We offer strong evidence that reduced toxicity occurs because extracellular dissolved organic carbon (DOC compounds produced by the algal cells themselves mitigate the toxicity of AgNPs. We analyzed this feedback with a dynamic model incorporating algal growth, nanoparticle dissolution, bioaccumulation of silver, DOC production and DOC-mediated inactivation of nanoparticles and ionic silver. Our findings demonstrate how the feedback between aquatic organisms and their environment may impact the toxicity and ecological effects of engineered nanoparticles.

  18. Synthesis and toxicity evaluation of hydrophobic ionic liquids for volatile organic compounds biodegradation in a two-phase partitioning bioreactor. (United States)

    Rodriguez Castillo, Alfredo Santiago; Guihéneuf, Solène; Le Guével, Rémy; Biard, Pierre-François; Paquin, Ludovic; Amrane, Abdeltif; Couvert, Annabelle


    Synthesis of several hydrophobic ionic liquids (ILs), which might be selected as good candidates for degradation of hydrophobic volatile organic compounds in a two-phase partitioning bioreactor (TPPB), were carried out. Several bioassays were also realized, such as toxicity evaluation on activated sludge and zebrafish, cytotoxicity, fluoride release in aqueous phase and biodegradability in order to verify their possible effects in case of discharge in the aquatic environment and/or human contact during industrial manipulation. The synthesized compounds consist of alkylimidazoliums, functionalized imidazoliums, isoqinoliniums, triazoliums, sulfoniums, pyrrolidiniums and morpholiniums and various counter-ions such as: PF6(-), NTf2(-) and NfO(-). Toxicity evaluation on activated sludge of each compound (5% v/v of IL) was assessed by using a glucose uptake inhibition test. Toxicity against zebrafish and cytotoxicity were evaluated by the ImPACCell platform of Rennes (France). Fluoride release in water was estimated by regular measurements using ion chromatography equipment. IL biodegradability was determined by measuring BOD28 of aqueous samples (compound concentration,1mM). All ILs tested were not biodegradable; while some of them were toxic toward activated sludge. Isoquinolinium ILs were toxic to human cancerous cell lines. Nevertheless no toxicity was found against zebrafish Danio rerio. Only one IL released fluoride after long-time agitation. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Amines and amine-related compounds in surface waters: a review of sources, concentrations and aquatic toxicity. (United States)

    Poste, Amanda E; Grung, Merete; Wright, Richard F


    This review compiles available information on the concentrations, sources, fate and toxicity of amines and amine-related compounds in surface waters, including rivers, lakes, reservoirs, wetlands and seawater. There is a strong need for this information, especially given the emergence of amine-based post-combustion CO2 capture technologies, which may represent a new and significant source of amines to the environment. We identify a broad range of anthropogenic and natural sources of amines, nitrosamines and nitramines to the aquatic environment, and identify some key fate and degradation pathways of these compounds. There were very few data available on amines in surface waters, with reported concentrations often below detection and only rarely exceeding 10 μg/L. Reported concentrations for seawater and reservoirs were below detection or very low, while for lakes and rivers, concentrations spanned several orders of magnitude. The most prevalent and commonly detected amines were methylamine (MA), dimethylamine (DMA), ethylamine (EA), diethylamine (DEA) and monoethanolamine (MEAT). The paucity of data may reflect the analytical challenges posed by determination of amines in complex environmental matrices at ambient levels. We provide an overview of available aquatic toxicological data for amines and conclude that at current environmental concentrations, amines are not likely to be of toxicological concern to the aquatic environment, however, the potential for amines to act as precursors in the formation of nitrosamines and nitramines may represent a risk of contamination of drinking water supplies by these often carcinogenic compounds. More research on the prevalence and toxicity of amines, nitrosamines and nitramines in natural waters is necessary before the environmental impact of new point sources from carbon capture facilities can be adequately quantified.

  20. Phototoxicology. 1. Light-enhanced toxicity of TNT and some related compounds to Daphnia magna and Lytechinus variagatus embryos. (United States)

    Davenport, R; Johnson, L R; Schaeffer, D J; Balbach, H


    Many environmental pollutants interact with solar near-ultraviolet (nuv) light in a manner which greatly increases their toxic effects. The phenomenon of light-mediated toxicity (phototoxicity) is only now becoming generally recognized to any significant degree. Manufacture of, and loading munitions with, the explosive 2,4,6-trinitrotoluene (TNT) in past decades caused contamination of soils and sediments at levels exceeding 1000 ppm and of waters at levels near saturation (100 ppm). Manufacture of TNT produces numerous nitrated by-products, and most of these compounds, including TNT, can be metabolized by many species, including bacteria, fungi, plants, and mammals. This study investigated the phototoxicity of TNT, and 2,3-, 2,4-, 2,6-, and 3,4-dinitrotoluene (DNT) and -diaminotoluene (DAT), and the major metabolites 2-amino-4,6-dinitrotoluene (2A) and 4-amino-2,6-dinitrotoluene (4A), to Daphnia magna (acute toxicity) and Lytechinus variagatus (sea urchin) embryos (subacute, developmental toxicity). Most of the compounds were weakly toxic or nontoxic in the dark. All were phototoxic to sea urchins. In D. magna, 2,3- and 3,4-DNT/DAT and 4A were not toxic but were phototoxic, and 2A was toxic and phototoxic; the other isomers were not toxic or phototoxic to this species.

  1. Real-time cell toxicity profiling of Tox21 10K compounds reveals cytotoxicity dependent toxicity pathway linkage. (United States)

    Hsieh, Jui-Hua; Huang, Ruili; Lin, Ja-An; Sedykh, Alexander; Zhao, Jinghua; Tice, Raymond R; Paules, Richard S; Xia, Menghang; Auerbach, Scott S


    Cytotoxicity is a commonly used in vitro endpoint for evaluating chemical toxicity. In support of the U.S. Tox21 screening program, the cytotoxicity of ~10K chemicals was interrogated at 0, 8, 16, 24, 32, & 40 hours of exposure in a concentration dependent fashion in two cell lines (HEK293, HepG2) using two multiplexed, real-time assay technologies. One technology measures the metabolic activity of cells (i.e., cell viability, glo) while the other evaluates cell membrane integrity (i.e., cell death, flor). Using glo technology, more actives and greater temporal variations were seen in HEK293 cells, while results for the flor technology were more similar across the two cell types. Chemicals were grouped into classes based on their cytotoxicity kinetics profiles and these classes were evaluated for their associations with activity in the Tox21 nuclear receptor and stress response pathway assays. Some pathways, such as the activation of H2AX, were associated with the fast-responding cytotoxicity classes, while others, such as activation of TP53, were associated with the slow-responding cytotoxicity classes. By clustering pathways based on their degree of association to the different cytotoxicity kinetics labels, we identified clusters of pathways where active chemicals presented similar kinetics of cytotoxicity. Such linkages could be due to shared underlying biological processes between pathways, for example, activation of H2AX and heat shock factor. Others involving nuclear receptor activity are likely due to shared chemical structures rather than pathway level interactions. Based on the linkage between androgen receptor antagonism and Nrf2 activity, we surmise that a subclass of androgen receptor antagonists cause cytotoxicity via oxidative stress that is associated with Nrf2 activation. In summary, the real-time cytotoxicity screen provides informative chemical cytotoxicity kinetics data related to their cytotoxicity mechanisms, and with our analysis, it is

  2. Toxic compounds and health and reproductive effects in St. Lawrence Beluga Whales

    Energy Technology Data Exchange (ETDEWEB)

    Beland, P.; Michaud, R. (St. Lawrence National Inst. of Ecotoxicology, Montreal, Quebec (Canada)); DeGuise, S. (St. Lawrence National Inst. of Ecotoxicology, Montreal, Quebec (Canada) Faculte de Medecine Veterinaire, St-Hyacinthe, Quebec (Canada)); Girard, C.; Lagace, A. (Faculte de Medecine Veterinaire, St-Hyacinthe, Quebec (Canada)); Martineau, D. (St. Lawrence National Inst. of Ecotoxicology, Montreal, Quebec (Canada) Cornell Univ., Ithaca, NY (United States)); Muir, D.C.G. (Freshwater Inst., Winnipeg, Manitoba (Canada)); Norstorm, R.J. (National Wildlife Research Center, Hull, Quebec (Canada)); Pelletier, E. (INRS-Oceanologie, Rimouski, Quebec (Canada)); Ray, S. (Fisheries and Oceans Canada, St. John' s, Newfoundland (Canada)) (and others)


    An epidemiologic study was carried out over a period of 9 years on an isolated population of beluga whales (Delphinapterus leucas) residing in the St. Lawrence estuary (Quebec, Canada). More than 100 individual deaths were aged, and/or autopsied and analyzed for toxic compounds, and the population was surveyed for size and structure. Arctic belugas and other species of whales and seals from the St. Lawrence were used for comparison. Population dynamics: Population size appeared to be stable and modeling showed this stable pattern to result from low calf production and/or low survival to adulthood. Toxicology: St. Lawrence belugas had higher or much higher levels of mercury, lead, PCBs, DDT, Mirex, benzo[a]pyrene metabolites, equivalent levels of dioxins, furans, and PAH metabolites, and much lower levels of cadmium than Arctic belugas. In other St. Lawrence cetaceans, levels of PCBs and DDT were inversely related to body size, as resulting from differences in metabolic rate, diet, and trophic position, compounded by length of residence in the St. Lawrence basin. St. Lawrence belugas had much higher levels than predicted from body size alone; levels increased with age in both sexes, although unloading by females through the placenta and/or lactation was evidenced by overall lower levels in females and very high burdens in some calves. 45 refs., 4 figs., 5 tabs.

  3. Volatile organic compounds of polyethylene vinyl acetate plastic are toxic to living organisms. (United States)

    Meng, Tingzhu Teresa


    Volatile organic compounds (VOCs) in polyvinyl chloride (PVC) plastic products readily evaporate; as a result, hazardous gases enter the ecosystem, and cause cancer in humans and other animals. Polyethylene vinyl acetate (PEVA) plastic has recently become a popular alternative to PVC since it is chlorine-free. In order to determine whether PEVA is harmful to humans, this research employed the freshwater oligochaete Lumbriculus variegatus as a model to compare their oxygen intakes while they were exposed to the original stock solutions of PEVA, PVC or distilled water at a different length of time for one day, four days or eight days. During the exposure periods, the oxygen intakes in both PEVA and PVC groups were much higher than in the distilled water group, indicating that VOCs in both PEVA and PVC were toxins that stressed L. variegatus. Furthermore, none of the worms fully recovered during the24-hr recovery period. Additionally, the L. variegatus did not clump together tightly after four or eight days' exposure to either of the two types of plastic solutions, which meant that both PEVA and PVC negatively affected the social behaviors of these blackworms. The LD50 tests also supported the observations above. For the first time, our results have shown that PEVA plastic has adverse effects on living organisms, and therefore it is not a safe alternative to PVC. Further studies should identify specific compounds causing the adverse effects, and determine whether toxic effect occurs in more complex organisms, especially humans.

  4. ATP-binding cassette and multidrug and toxic compound extrusion transporters in plants: a common theme among diverse detoxification mechanisms. (United States)

    Shoji, Tsubasa


    Plants have developed elaborate detoxification mechanisms to cope with a large number of potentially toxic compounds, which include exogenous xenobiotics and endogenous metabolites, especially secondary metabolites. After enzymatic modification or synthesis, such compounds are transported and accumulated in apoplastic cell walls or central vacuoles in plant cells. Membrane transporters actively catalyze translocation of a diverse range of these compounds across various membranes within cells. Biochemical, molecular, and genetic studies have begun to reveal functions of a handful of ATP-binding cassette and multidrug and toxic compound extrusion family transporters engaged in transport of organic xenobiotics, heavy metals, metalloids, aluminum, alkaloids, flavonoids, terpenoids, terpenoid-derived phytohormones, cuticle lipids, and monolignols in plants. This detoxification versatility and metabolic diversity may underlie the functional diversification in plants of these families of transporters, which are largely involved in multidrug resistance in microorganisms and animals. © 2014 Elsevier Inc. All rights reserved.

  5. Rapid toxicity testing based on yeast respiratory activity

    Energy Technology Data Exchange (ETDEWEB)

    Haubenstricker, M.E. (Environmental Protection Agency, Ann Arbor, MI (USA)); Meier, P.G.; Mancy, K.H. (Univ. of Michigan, Ann Arbor (USA)); Brabec, M.J. (Eastern Michigan Univ., Ypsilanti (USA))


    Rapid and economical techniques are needed to determine the effects of environmental contaminants. At present, the main methods to assess the impact of pollutants are based on chemical analysis of the samples. Invertebrate and vertebrate exposures have been used over the last two decades in assessing acute and chronic toxicities. However, these tests are labor intensive and require several days to complete. An alternative to whole organism exposure is to determine toxic effects in monocellular systems. Another approach for assessing toxicity is to monitor sensitive, nonspecific, subcellular target sites such as mitochondria. Changes in mitochondrial function which could indicate a toxic effect can be demonstrated readily after addition of a foreign substance. In initial assessments of various chemicals, rat liver mitochondria (RLM) were evaluated as a biological sensor of toxicity. False toxicity assessments will result if these ions are present even though they are generally considered nontoxic. Because of these disadvantages, an alternative mitochondrial system, such as found in bakers yeast, was evaluated.

  6. Synthesis and toxicity evaluation of hydrophobic ionic liquids for volatile organic compounds biodegradation in a two-phase partitioning bioreactor

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Castillo, Alfredo Santiago [Ecole Nationale Supérieure de Chimie de Rennes, CNRS, UMR 6226, 11 Allée de Beaulieu, CS 50837, 35708 Rennes Cedex 7 (France); Université européenne de Bretagne (France); Guihéneuf, Solène, E-mail: [Université européenne de Bretagne, Université de Rennes 1, Sciences Chimiques de Rennes, UMR, CNRS 6226, Groupe Ingénierie Chimique & Molécules Pour le Vivant (ICMV), Bât. 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 Rennes cedex (France); Le Guével, Rémy [Plate-forme ImPACcell Structure Fédérative de Recherche BIOSIT Université de Rennes 1, Bat. 8, Campus de Villejean, 2 Avenue du Pr. Leon Bernard, CS 34317, 35043 Rennes Cedex (France); Biard, Pierre-François [Ecole Nationale Supérieure de Chimie de Rennes, CNRS, UMR 6226, 11 Allée de Beaulieu, CS 50837, 35708 Rennes Cedex 7 (France); Université européenne de Bretagne (France); and others


    Highlights: • Description of a VOC depollution system suitable with industrial processes, TPPB. • Novel association of TPPB and hydrophobic ionic liquids. • Synthesis of several hydrophobic ionic liquids designed to fit desired properties. • Toxicity evaluation of these ILs towards cells, animals and bacteria. - Abstract: Synthesis of several hydrophobic ionic liquids (ILs), which might be selected as good candidates for degradation of hydrophobic volatile organic compounds in a two-phase partitioning bioreactor (TPPB), were carried out. Several bioassays were also realized, such as toxicity evaluation on activated sludge and zebrafish, cytotoxicity, fluoride release in aqueous phase and biodegradability in order to verify their possible effects in case of discharge in the aquatic environment and/or human contact during industrial manipulation. The synthesized compounds consist of alkylimidazoliums, functionalized imidazoliums, isoqinoliniums, triazoliums, sulfoniums, pyrrolidiniums and morpholiniums and various counter-ions such as: PF{sub 6}{sup −}, NTf{sub 2}{sup −} and NfO{sup −}. Toxicity evaluation on activated sludge of each compound (5% v/v of IL) was assessed by using a glucose uptake inhibition test. Toxicity against zebrafish and cytotoxicity were evaluated by the ImPACCell platform of Rennes (France). Fluoride release in water was estimated by regular measurements using ion chromatography equipment. IL biodegradability was determined by measuring BOD{sub 28} of aqueous samples (compound concentration,1 mM). All ILs tested were not biodegradable; while some of them were toxic toward activated sludge. Isoquinolinium ILs were toxic to human cancerous cell lines. Nevertheless no toxicity was found against zebrafish Danio rerio. Only one IL released fluoride after long-time agitation.

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

    Energy Technology Data Exchange (ETDEWEB)

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


    A study to determine the acute and chronic toxicity of uranyl nitrate, hydrogen uranyl phosphate, and uranium dioxide to the organism Ceriodaphnia dubia was conducted. The toxicity tests were conducted by two independent environmental consulting laboratories. Part of the emphasis for this determination was based on concerns expressed by SCDHEC, which was concerned that a safety factor of 100 must be applied to the previous 1986 acute toxicity result of 0.22 mg/L for Daphnia pulex, This would have resulted in the LETF release limits being based on an instream concentration of 0.0022 mg/L uranium. The NPDES Permit renewal application to SCDHEC utilized the results of this study and recommended that the LETF release limit for uranium be based an instream concentration of 0.004 mg/L uranium. This is based on the fact that the uranium releases from the M-Area LETF will be in the hydrogen uranyl phosphate form, or a uranyl phosphate complex at the pH (6--10) of the Liquid Effluent Treatment Facility effluent stream, and at the pH of the receiving stream (5.5 to 7.0). Based on the chronic toxicity of hydrogen uranyl phosphate, a lower uranium concentration limit for the Liquid Effluent Treatment Facility outfall vs. the existing NPDES permit was recommended: The current NPDES permit ``Guideline`` for uranium at outfall M-004 is 0.500 mg/L average and 1.0 mg/L maximum, at a design flowrate of 60 gpm. It was recommended that the uranium concentration at the M-004 outfall be reduced to 0.28 mg/L average, and 0.56 mg/L, maximum, and to reduce the design flowrate to 30 gpm. The 0.28 mg/L concentration will provide an instream concentration of 0.004 mg/L uranium. The 0.28 mg/L concentration at M-004 is based on the combined flows from A-014, A-015, and A-011 outfalls (since 1985) of 1840 gpm (2.65 MGD) and was the flow rate which was utilized in the 1988 NPDES permit renewal application.

  8. The heavy metal ions (Cu2+, Zn2+, Cd+) toxic compounds influence on triticale plants growth (United States)

    Brezoczki, V. M.; Filip, G. M.


    The presence of the heavy metals toxic compounds (CuSO4 · 5H2O, ZnSO4 · 7H2O and 3CdSO4·8H2O) in water and soil can be observed by their negative effects on the germination and growth process for different vegetable (barley, oat, maize) who are used for human and animal consumption. This paper it aims the determination of germination and growth inhibition negative effects for triticale plants in the heavy metals ions presence by ecotoxicological laboratory tests. The triticale plants was chosen for their different characteristics to the other grasses respectively: a very good resistance for a wide range of diseases, an accelerated growth and a very good tolerance for aluminum ions presents in acid soils. The determinations were conducted step by step, first, we put the triticale grains in contact with the heavy metal solutions with different concentration then for 3 days we noticed the triticale germination inhibition effects and finally we noticed the growth inhibition process for triticale plants respectively in 7th and 9th day from the start of the experiment. At the end of the tests we can conclude that the triticale roots have a very great sensibility to a CuSO4 solutions compared to the effects for their stalks. A positive effect for triticale stalks we can see for low CuSO4 solution concentrations thus for 5 mg Cu/l the growth is 19,44%. A positive effect for triticale roots it can see for low ZnSO4 solution concentrations so for 5 - 15 mg Zn/l the growth is 24,4%. In the presence of the CdSO4 solution all the processes are inhibited (germination and growth for triticale plants) even for a low concentrations for this toxic.

  9. Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity. (United States)

    Xia, Tian; Korge, Paavo; Weiss, James N; Li, Ning; Venkatesen, M Indira; Sioutas, Constantinos; Nel, Andre


    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)-enriched aromatic fraction in O2 .- generation, decrease of membrane potential (Delta-Psi m), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)-sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on Delta-Psi m at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in Delta-Psi m at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and Delta-Psi m are mediated by adsorbed chemicals rather than the particles themselves.

  10. Research strategies for design and development of NSAIDs: clue to balance potency and toxicity of acetanilide compounds. (United States)

    Pal, A K; Sen, S; Ghosh, S; Bera, A K; Bhattacharya, S; Chakraborty, S; Banerjee, A


    Despite the fact that many modern drug therapies are based on the concept of enzyme inhibition, inhibition of several enzymes leads to pathological disorders. Clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) bind to the active site of the membrane protein, cyclooxygenase (COX) and inhibit the synthesis of prostaglandins, the mediators for causing inflammation. At the same time, inhibition of hepatic cysteine proteases by some NSAID metabolites like NAPQI is implicated in the pathogenesis of hepatotoxicity. As a part of our efforts to develop new effective NSAIDs, a comprehensive investigation starting from synthesis to the study of the final metabolism of acetanilide group of compound has been envisaged with appropriate feedback from kinetic studies to enhance our knowledge and technical competency to feed the know-how to the medicinal chemist to screen out and design new acetanilide derivatives of high potency and low toxicity. Structure-function relationship based on the interaction of acetanilide with its cognate enzyme, cyclooxygenase has been studied critically with adequate comparison with several other available crystal structures of COX-NSAID complexes. Furthermore, to make the receptor based drug design strategy a novel and comprehensive one, both the mechanism of metabolism of acetanilide and structural basis of inhibition of cysteine proteases by the reactive metabolite (NAPQI) formed by cytochrome P450 oxidation of acetanilide have been incorporated in the study. It is hoped that this synergistic approach and the results obtained from such consorted structural investigation at atomic level may guide to dictate synthetic modification with judicious balance between cyclooxygenase inhibition and hepatic cysteine protease inhibition to enhance the potential of such molecular medicine to relieve inflammation on one hand and low hepatic toxicity on the other.

  11. [Health effects of solar cell component material. Toxicity of indium compounds to laboratory animals determined by intratracheal instillations]. (United States)

    Tanaka, Akiyo; Hirata, Miyuki


    Owing to the increasing interest being paid to the issue of the global environment, the production of solar cells has increased rapidly in recent years. Copper indium gallium diselenide (CIGS) is a new efficient thin film used in some types of solar cell. Indium is a constitutive element of CIGS thin-film solar cells. It was thought that indium compounds were not harmful until the beginning of the 1990s because there was little information regarding the adverse health effects on humans or animals arising from exposure to indium compounds. After the mid-1990s, data became available indicating that indium compounds can be toxic to animals. In animal studies, it has been clearly demonstrated that indium compounds cause pulmonary toxicity and that the dissolution of indium compounds in the lungs is considerably slow, as shown by repeated intratracheal instillations in experimental animals. Thus, it is necessary to pay much greater attention to human exposure to indium compounds, and precautions against possible exposure to indium compounds are paramount with regard to health management.

  12. Tissue-binding and toxicity of compounds structurally related to the herbicide dichlobenil in the mouse olfactory mucosa. (United States)

    Eriksson, C; Brandt, I; Brittebo, E


    The herbicides dichlobenil (2,6-dichlorobenzonitrile), chlorthiamid (2,6-dichlorothiobenzamide) and their environmental degradation product 2,6-dichlorobenzamide are irreversibly bound and toxic to the olfactory mucosa following single injections in mice (Brandt et al., Toxicology and Applied Pharmacology 1990, 103, 491-501; Brittebo et al., Fundamental and Applied Toxicology 1991, 17, 92-102). In the present study, autoradiography showed an irreversible binding of radioactivity in the olfactory mucosa (preferentially in the Bowman's glands) in C57Bl/6 mice treated with the 14C-labelled analogues [14C]2,6-difluorobenzonitrile ([14C]DFBN) and [14C]2,6-difluorobenzamide ([14C]DFBA). Therefore the toxicity of DFBN, DFBA and of some structurally related compounds including benzonitrile (BN) and the herbicides bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) and ioxynil (3,5-diiodo-4-hydroxybenzonitrile) in the mouse olfactory mucosa was examined. No histopathological changes in the olfactory mucosa or in the liver were observed following a single ip dose of any of these compounds [0.145 mmol/kg (all compounds); 0.58 mmol/kg (DFBN, DFBA and BN)]. Also in mice treated with the glutathione-depleting agent phorone, none of these compounds induced any histopathological changes in the olfactory mucosa. The covalent binding of [14C]DFBN in the olfactory mucosa was 16 times lower than an equimolar toxic dose of [14C]dichlobenil, suggesting a low rate of metabolic activation of DFBN in the olfactory mucosa or a low reactivity of the DFBN metabolites formed. The results of this study thus show that single doses of DFBN, DFBA, BN, IX and BX, compounds structurally related to the potent olfactory toxicant dichlobenil, do not elicit acute toxicity in the olfactory mucosa of mice.

  13. Mammalian Toxicity of Munitions Compounds. Phase I. Acute Oral Toxicity, Primary Skin and Eye Irritation, Dermal Sensitization, Disposition and Metabolism and Ames Tests of Additional Compounds (United States)


    Assay of 300 Chemicals, Proc. Nat. Acad. Sci., 72:5135-5139, 1975. 17. Wang, C. Y., K. Muraoka, and G. T. Bryan, Yatagenicity of Nitrofurans ...L. H. DiSalvo, and J. Ng, Toxicity and Mutagenicity of 2,4,6-Trinitrotoluene and Its Microbial Metabolites , Appl. Environ. Microbiol., 31:576-580

  14. Structure of a cation-bound multidrug and toxic compound extrusion transporter

    Energy Technology Data Exchange (ETDEWEB)

    He, Xiao; Szewczyk, Paul; Karyakin, Andrey; Evin, Mariah; Hong, Wen-Xu; Zhang, Qinghai; Chang, Geoffrey (Scripps)


    Transporter proteins from the MATE (multidrug and toxic compound extrusion) family are vital in metabolite transport in plants, directly affecting crop yields worldwide. MATE transporters also mediate multiple-drug resistance (MDR) in bacteria and mammals, modulating the efficacy of many pharmaceutical drugs used in the treatment of a variety of diseases. MATE transporters couple substrate transport to electrochemical gradients and are the only remaining class of MDR transporters whose structure has not been determined. Here we report the X-ray structure of the MATE transporter NorM from Vibrio cholerae determined to 3.65 {angstrom}, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known MDR transporter. We also report a cation-binding site in close proximity to residues previously deemed critical for transport. This conformation probably represents a stage of the transport cycle with high affinity for monovalent cations and low affinity for substrates.

  15. Consequences of toxic secondary compounds in nectar for mutualist bees and antagonist butterflies. (United States)

    Jones, Patricia L; Agrawal, Anurag A


    Attraction of mutualists and defense against antagonists are critical challenges for most organisms and can be especially acute for plants with pollinating and non-pollinating flower visitors. Secondary compounds in flowers have been hypothesized to adaptively mediate attraction of mutualists and defense against antagonists, but this hypothesis has rarely been tested. The tissues of milkweeds (Asclepias spp.) contain toxic cardenolides that have long been studied as chemical defenses against herbivores. Milkweed nectar also contains cardenolides, and we have examined the impact of manipulating cardenolides in nectar on the foraging choices of two flower visitors: generalist bumble bees, Bombus impatiens, which are mutualistic pollinators, and specialist monarch butterflies, Danaus plexippus, which are herbivores as larvae and ineffective pollinators as adults. Although individual bumble bees in single foraging bouts showed no avoidance of cardenolides at the highest natural concentrations reported for milkweeds, a pattern of deterrence did arise when entire colonies were allowed to forage for several days. Monarch butterflies were not deterred by the presence of cardenolides in nectar when foraging from flowers, but laid fewer eggs on plants paired with cardenolide-laced flowers compared to controls. Thus, although deterrence of bumble bees by cardenolides may only occur after extensive foraging, a primary effect of nectar cardenolides appears to be reduction of monarch butterfly oviposition.

  16. Quaternary ammonium compounds (QACs): a review on occurrence, fate and toxicity in the environment. (United States)

    Zhang, Chang; Cui, Fang; Zeng, Guang-ming; Jiang, Min; Yang, Zhong-zhu; Yu, Zhi-gang; Zhu, Meng-ying; Shen, Liu-qing


    Quaternary ammonium compounds (QACs) are widely applied in household and industrial products. Most uses of QACs can be expected to lead to their release to wastewater treatment plants (WWTPs) and then dispersed into various environmental compartments through sewage effluent and sludge land application. Although QACs are considered to be aerobically biodegradable, the degradation is affected by its chemical structures, dissolved oxygen concentration, complexing with anionic surfactants, etc. High abundance of QACs has been detected in sediment and sludge samples due to its strong sorption and resistance to biodegradation under anoxic/anaerobic conditions. QACs are toxic to a lot of aquatic organisms including fish, daphnids, algae, rotifer and microorganisms employed in wastewater treatment systems. And antibiotic resistance has emerged in microorganisms due to excessive use of QACs in household and industrial applications. The occurrence of QACs in the environment is correlated with anthropogenic activities, such as wastewater discharge from WWTPs or single source polluters, and sludge land application. This article also reviews the analytical methods for determination of QACs in environmental compartments including surface water, wastewater, sewage sludge and sediments. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Analysis of a ToxCast™ HTS Toxicity Signature for putative Vascular Disruptor Compounds (United States)

    Recent studies have shown the importance of blood vessel formation during embryo development and the strong correlation to developmental toxicity. Several developmental toxicants, such as thalidomide, have been identified which specifically target the forming embryonic vasculatur...

  18. In silico identification of potential drug compound against Peroxisome proliferator-activated receptor-gamma by virtual screening and toxicity studies for the treatment of Diabetic Nephropathy. (United States)

    Singh, Smrita; Mohanty, Aparajita


    Diabetic Nephropathy is a serious complication of diabetes mellitus. Current therapeutic strategies of Diabetic Nephropathy are based on control of modifiable risks like hypertension, glucose levels, and dyslipidemia. Peroxisome proliferator activated receptor-gamma (PPAR-γ) is implicated in several metabolic syndromes including Diabetic Nephropathy, besides obesity, insulin insensitivity, dislipidemia, inflammation, and hypertension. In the present study, virtual screening of 617 compounds from two different public databases was done against PPAR-γ with an objective to find a possible lead compound. Two softwares, PyRx and iGEMDOCK, were used to achieve the docking accuracy in order to avoid loss of candidate compounds. Rosiglitazone (used to treat Diabetic Nephropathy) was taken as the standard compound. A total of 30 compounds with good binding affinity with PPAR-γ were selected for further filtering, on the basis of absorption, distribution, metabolism, excretion, and toxicity (ADMET). The interaction profiling of these 30 compounds, showed a minimum of one and maximum of three interactions with reference to rosiglitazone (SER-289, HIS-449, HIS-323, TYR-473). The fulfilling of ADMET analysis criteria of 30 compounds led to the selection of four compounds (ZINC ID 00181552, 00276456, 00298314, 00448009). Molecular dynamics simulation of these lead compounds in complex with PPAR-γ revealed that three of the four compounds formed a stable complex in the ligand-binding pocket of PPAR-γ during 20-ns simulation. Hence, these three (ZINC ID 00181552, 00276456, 00298314) of the four compounds are potential candidates for experimental validation of biological activity against PPAR-γ in future drug discovery studies.

  19. A Generally Applicable Computer Algorithm Based on the Group Additivity Method for the Calculation of Seven Molecular Descriptors: Heat of Combustion, LogPO/W, LogS, Refractivity, Polarizability, Toxicity and LogBB of Organic Compounds; Scope and Limits of Applicability. (United States)

    Naef, Rudolf


    A generally applicable computer algorithm for the calculation of the seven molecular descriptors heat of combustion, logPoctanol/water, logS (water solubility), molar refractivity, molecular polarizability, aqueous toxicity (protozoan growth inhibition) and logBB (log (cblood/cbrain)) is presented. The method, an extendable form of the group-additivity method, is based on the complete break-down of the molecules into their constituting atoms and their immediate neighbourhood. The contribution of the resulting atom groups to the descriptor values is calculated using the Gauss-Seidel fitting method, based on experimental data gathered from literature. The plausibility of the method was tested for each descriptor by means of a k-fold cross-validation procedure demonstrating good to excellent predictive power for the former six descriptors and low reliability of logBB predictions. The goodness of fit (Q²) and the standard deviation of the 10-fold cross-validation calculation was >0.9999 and 25.2 kJ/mol, respectively, (based on N = 1965 test compounds) for the heat of combustion, 0.9451 and 0.51 (N = 2640) for logP, 0.8838 and 0.74 (N = 1419) for logS, 0.9987 and 0.74 (N = 4045) for the molar refractivity, 0.9897 and 0.77 (N = 308) for the molecular polarizability, 0.8404 and 0.42 (N = 810) for the toxicity and 0.4709 and 0.53 (N = 383) for logBB. The latter descriptor revealing a very low Q² for the test molecules (R² was 0.7068 and standard deviation 0.38 for N = 413 training molecules) is included as an example to show the limits of the group-additivity method. An eighth molecular descriptor, the heat of formation, was indirectly calculated from the heat of combustion data and correlated with published experimental heat of formation data with a correlation coefficient R² of 0.9974 (N = 2031).

  20. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    NARCIS (Netherlands)

    Theunissen, P.T.; Robinson, J.F.; Pennings, J.L.A.; van Herwijnen, M.; Kleinjans, J.C.S.; Piersma, A.H.


    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may fur

  1. A New Nonlinear Compound Forecasting Method Based on ANN

    Institute of Scientific and Technical Information of China (English)


    In this paper the compound-forecasting method is discussed. The compound-forecasting method is one of the hotspots in the current predication. Firstly, the compound-forecasting method is introduced and various existing compound-forecasting methods arediscussed. Secondly, the Artificial Neural Network (ANN) is brought in compound-prediction research and a nonlinear compound-prediction model based on ANN is presented. Finally, inorder to avoid irregular weight, a new method is presented which uses principal component analyses to increase the availability of compound-forecasting information. Higherforecasting precision is achieved in practice.

  2. Bioavailability-based toxicity endpoints of bifenthrin for Hyalella azteca and Chironomus dilutus. (United States)

    Harwood, Amanda D; Landrum, Peter F; Lydy, Michael J


    Recent studies have determined that techniques, such as solid phase microextraction (SPME) fibers and Tenax beads, can predict bioaccumulation and potentially could predict toxicity for several compounds and species. Toxicity of bifenthrin was determined using two standard sediment toxicity tests with the benthic species Hyalella azteca and Chironomus dilutus in three reference sediments with different characteristics. The objectives of the current study were to establish bioavailability-based median lethal concentrations (LC50) and median effect concentrations (EC50) of the pyrethroid insecticide bifenthrin, compare their ability to assess toxicity to the use of whole sediment concentrations, as well as to make comparisons of the concentrations derived using each method in order to make assessments of accuracy and extrapolation potential. Four metrics were compared including SPME fiber concentration, pore water concentration derived using SPMEs, 6 h Tenax extractable concentration, and 24 h Tenax extractable concentration. The variation among the LC50s and EC50s in each sediment derived using bioavailability-based methods was comparable to variation among organic carbon normalized sediment concentrations, but improved over whole sediment concentrations. There was a significant linear relationship between SPME or Tenax and organic carbon normalized sediment concentrations. Additionally, there was a significant relationship between the SPME and Tenax concentrations across sediments. The significant linear relationship between SPME and Tenax concentrations further demonstrates that these bioavailability-based endpoints are interrelated. This study derived bioavailability-based benchmarks that may prove to be more accurate than sediment-based ones in predicting toxicity across sediment types.

  3. Prediction and assessment of mixture toxicity of compounds in antifouling paints using the sea-urchin embryo-larval bioassay. (United States)

    Bellas, Juan


    The ecotoxicological assessment of alternative "booster" biocides is urgently needed in order to develop environmentally acceptable antifouling paints. However, research has focused mainly on single compounds, and there is still a lack of data on their mixture toxicity. The present study investigated the single and mixture toxicity of three of the most widely used antifouling biocides: zinc pyrithione, chlorothalonil and Sea-Nine, using the sea-urchin (Paracentrotus lividus) embryo-larval bioassay. Also, the predictive ability of the concentration addition (CA) and independent action (IA) concepts for antifouling mixtures was evaluated. Both concepts failed to accurately predict the toxicity of the antifouling mixtures, with the exception of the zinc pyrithione and Sea-Nine mixture, which was accurately predicted by the IA concept, suggesting a dissimilar mode of action of those substances. In general, CA predicted consistently higher toxicity than IA; however, CA overestimated the toxicity of the studied mixtures by a factor of only 1.6, representing a reasonable worst-case approach to be used in the predictive hazard assessment of antifouling mixtures. Finally, the present study demonstrates that the risk of antifouling mixtures for the early developmental stages of sea urchin is higher than the risk of each single substance, and therefore, the inclusion of mixture considerations in the development of water quality criteria for antifouling compounds is strongly recommended.

  4. Assessment of chimeric mice with humanized livers in new drug development: generation of pharmacokinetics, metabolism and toxicity data for selecting the final candidate compound. (United States)

    Kamimura, Hidetaka; Ito, Satoshi


    1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.

  5. Toxicity Assessment of Atrazine and Related Triazine Compounds in the Microtox Assay, and Computational Modeling for Their Structure-Activity Relationship

    Directory of Open Access Journals (Sweden)

    Jerzy Leszczynski


    Full Text Available The triazines are a group of chemically similar herbicides including atrazine, cyanazine, and propazine, primarily used to control broadleaf weeds. About 64 to 80 million lbs of atrazine alone are used each year in the United States, making it one of the two most widely used pesticides in the country. All triazines are somewhat persistent in water and mobile in soil. They are among the most frequently detected pesticides in groundwater. They are considered as possible human carcinogens (Group C based on an increase in mammary gland tumors in female laboratory animals. In this research, we performed the Microtox Assay to investigate the acute toxicity of a significant number of triazines including atrazine, atraton, ametryne, bladex, prometryne, and propazine, and some of their degradation products including atrazine desethyl, atrazine deisopropyl, and didealkyled triazine. Tests were carried out as described by Azur Environmental [1]. The procedure measured the relative acute toxicity of triazines, producing data for the calculation of triazine concentrations effecting 50% reduction in bioluminescence (EC50s. Quantitative structure-activity relationships (QSAR were examined based on the molecular properties obtained from quantum mechanical predictions performed for each compound. Toxicity tests yielded EC50 values of 39.87, 273.20, 226.80, 36.96, 81.86, 82.68, 12.74, 11.80, and 78.50 mg/L for atrazine, propazine, prometryne, atraton, atrazine desethyl, atrazine deisopropyl, didealkylated triazine, ametryne, and bladex, respectively; indicating that ametryne was the most toxic chemical while propazine was the least toxic. QSAR evaluation resulted in a coefficient of determination (r2 of 0.86, indicating a good value of toxicity prediction based on the chemical structures/properties of tested triazines.

  6. Degradation and conversion of toxic compounds into useful bioplastics by Cupriavidus sp. CY-1: relative expression of the PhaC gene under phenol and nitrogen stress


    MOTAKATLA, Venkateswer Reddy; YAJIMA, Yuka; MAWATARI, Yasuteru; Hoshino, Tamotsu; CHANG, Young-Cheol


    In this study different types of toxic compounds, i.e., alkylphenols, mono and poly-aromatic hydrocarbons were converted into polyhydroxybutyrate (PHB) using the isolated bacteria Cupriavidus sp. CY-1. The influence of Tween-80 on the toxic compound degradation ability of CY-1 was analyzed using high pressure liquid chromatography. Among all the compounds, CY-1 showed the highest removal of naphthalene (100 ± 6%), followed by phenol (96 ± 7%), and the lowest removal of alkylphenols without Tw...

  7. Toxicity of Military Unique Compounds in Aquatic Organisms: An Annotated Bibliography (Studies Published Through 1996) (United States)


    Biochemistry/Air Pollution/Soil Pollutants/Water. Haley, M. V., Checkai, R. T., Kurnas , C. W., and Wentsel, R. S. Toxicity Determination of Explosive...Membranes/Metals/Operations/Residues/Sites/Soil Surveys/ Toxicity/Water/Hazardous Materials/Contamination/Explosives/ Response. Haley, M. V., and Kurnas ... Kurnas , C. W., Chester, N. A., and Muse, W. T. Aquatic Toxicity of the Decontamination Agent: Multipurpose (DAM) Decontamination Solution. Giveth

  8. Fast and sensitive optical toxicity bioassay based on dual wavelength analysis of bacterial ferricyanide reduction kinetics. (United States)

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


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

  9. General synthesis of carbon nanocages and their adsorption of toxic compounds from cigarette smoke (United States)

    Li, Guangda; Yu, Hongxiao; Xu, Liqiang; Ma, Qiang; Chen, Chao; Hao, Qin; Qian, Yitai


    Carbon nanocages (CNCs) have been synthesized through a simple approach using different alcohols and ferrous oxalate as reactants at 550 °C for 12 h in a sealed autoclave. The lengths of the sides of the CNCs are about 200-350 nm and the wall thicknesses are about 10-15 nm. The formation mechanism of the CNCs is also discussed, based on the experimental results. These CNCs show excellent removal efficiency for phenolic compounds, ammonia, and total particulate matter from cigarette smoke. The adsorption capability of CNCs prepared from ethanol is much higher than that of other samples. For example, the efficiency of 5 mg CNCs (ethanol) for removing the six phenolic compounds p-dihydroxybenzene, m-dihydroxybenzene, o-dihydroxybenzene, phenol, m-cresol, and o-cresol can reach 57.31%, 62.25%, 65.58%, 75.95%, 54.34% and 59.43%, respectively, while that of the commercial activated carbon (5 mg) can only reach 29.02%, 33.93%, 35.00%, 36.00%, 20.33% and 36.19%, respectively, under the same conditions.Carbon nanocages (CNCs) have been synthesized through a simple approach using different alcohols and ferrous oxalate as reactants at 550 °C for 12 h in a sealed autoclave. The lengths of the sides of the CNCs are about 200-350 nm and the wall thicknesses are about 10-15 nm. The formation mechanism of the CNCs is also discussed, based on the experimental results. These CNCs show excellent removal efficiency for phenolic compounds, ammonia, and total particulate matter from cigarette smoke. The adsorption capability of CNCs prepared from ethanol is much higher than that of other samples. For example, the efficiency of 5 mg CNCs (ethanol) for removing the six phenolic compounds p-dihydroxybenzene, m-dihydroxybenzene, o-dihydroxybenzene, phenol, m-cresol, and o-cresol can reach 57.31%, 62.25%, 65.58%, 75.95%, 54.34% and 59.43%, respectively, while that of the commercial activated carbon (5 mg) can only reach 29.02%, 33.93%, 35.00%, 36.00%, 20.33% and 36.19%, respectively, under

  10. Mechanochemical reactions on copper-based compounds

    NARCIS (Netherlands)

    Castricum, H.L.; Bakker, H.; Poels, E.K.


    Mechanochemical reactions of copper and copper oxides with oxygen and carbon dioxide are discussed, as well as decomposition and reduction of copper compounds by mechanical milling under high-vacuum conditions.

  11. 14-day toxicity studies of tetravalent and pentavalent vanadium compounds in Harlan Sprague Dawley rats and B6C3F1/N mice via drinking water exposure

    Directory of Open Access Journals (Sweden)

    Georgia K. Roberts


    Conclusions: Based on clinical observations and overt toxicity, sodium metavanadate appears to be more toxic than vanadyl sulfate. Differential toxicity cannot be explained by differences in total vanadium intake, based on water consumption, and may be due to differences in disposition or mechanism of toxicity.

  12. A Comparative Study of Two Quantum Chemical Descriptors in Predicting Toxicity of Aliphatic Compounds towards Tetrahymena pyriformis

    Directory of Open Access Journals (Sweden)

    Altaf Hussain Pandith


    Full Text Available Quantum chemical parameters such as LUMO energy, HOMO energy, ionization energy (I, electron affinity (A, chemical potential (μ, hardness (η electronegativity (χ, philicity (ωα, and electrophilicity (ω of a series of aliphatic compounds are calculated at the B3LYP/6-31G(d level of theory. Quantitative structure-activity relationship (QSAR models are developed for predicting the toxicity (pIGC50 of 13 classes of aliphatic compounds, including 171 electron acceptors and 81 electron donors, towards Tetrahymena pyriformis. The multiple linear regression modeling of toxicity of these compounds is performed by using the molecular descriptor log P (1-octanol/water partition coefficient in conjunction with two other quantum chemical descriptors, electrophilicity (ω and energy of the lowest unoccupied molecular orbital (ELUMO. A comparison is made towards the toxicity predicting the ability of electrophilicity (ω versus ELUMO as a global chemical reactivity descriptor in addition to log P. The former works marginally better in most cases. There is a slight improvement in the quality of regression by changing the unit of IGC50 from mg/L to molarity and by removing the racemates and the diastereoisomers from the data set.

  13. Toxicity-based assessment of the treatment performance of wastewater treatment and reclamation processes

    Institute of Scientific and Technical Information of China (English)

    Dongbin Wei; Zhuowei Tan; Yuguo Du


    The reclamation and reuse of wastewater is one of the possible ways to relieve the serious fresh water resource crisis in China.Efficient reclamation treatment technologies ensure the safe reuse of reclaimed water.In order to screen out and evaluate technologies appropriate for reclamation treatment,a great deal of efforts have been brought to bear.In the present study,a toxicity-based method including a Photobacterium phosphorewn test for acute toxicity and SOS/umu test for genotoxicity,accompanied by the traditional physicochemical parameters DOC (dissolved organic carbon) and UV254 (absorbance at 254 nm),was used to measure the treatment performance of different reclamation processes,including the anaerobic-anoxic-oxic biological process (A2O) and subsequent physical/chemical reclamation processes (ultrafiltration,ozonation,chlorination).It was found that for the secondary effluent after the A2O process,both the toxicity and physicochemical indices had greatly decreased compared with those of the influent.However,chemical reclamation processes such as ozonation and chlorination could possibly raise toxicity levels again.Fortunately,the toxicity elevation could be avoided by optimizing the ozone dosage and using activated carbon after ozonation.It was noted that by increasing the ozone dosage to 10 mg/L and employing activated carbon with more than 10 min hydraulic retention time,toxicity elevation was controlled.Furthermore,it was shown that pre-ozonation before activated carbon and chlorination played an important role in removing organic compounds and reducing the toxicity formation potential.The toxicity test could serve as a valuable tool to evaluate the performance of reclamation processes.

  14. Synthesis Organonitrogen Compounds from Patchouli Alcohol Through Ritter Reaction with Acetonitrile and Its Toxicity to Artemia salina Leach.

    Directory of Open Access Journals (Sweden)

    Khoirun Nisyak


    Full Text Available Patchouli oil contains a compound with biological activities to human body called the patchouli alcohol that can be further developed in medical field. This research aimed to synthesize organonitrogen compound from patchouli alcohol through Ritter reaction with acetonitrile and discover its toxicity towards Artemia salina Leach. The isolation of patchouli alcohol from patchouli oil using fractional distillation under reduced pressure method. The synthesis of organonitrogen compound is done at room temperature with the mol ratio of patchouli alcohol: acetonitrile: sulfuric acid is 1:1,5:4 for 24 hours. The result showed that the amount of patchouli alcohol produced from fractional distillation is 65,25%. The main product yielded from the synthesis between patchouli alcohol and acetonitrile through Ritter reaction is 36,93 % of N-(4,8a,9,9-tetramethyl decahydro-1,6-methanonaphtalene-1-yl acetamide. Starting material used have LC50 of 77,39 ppm. The product of synthesis have higher toxicity level than starting material, which have LC50 value is 10,39 ppm with the potential as medical compounds.

  15. Analysis of the methodology to determine anaerobic toxicity: evaluation of main compounds present in wastewater treatment plants (WWTPs). (United States)

    Urra, J; Poirrier, P; Segovia, J; Lesty, Y; Chamy, R


    The influence of the concentration of biomass on the level of inhibition and anaerobic degradation kinetics in batch systems was studied with toxic compounds that can generate destabilization in the operation of sludge anaerobic digesters. The compounds were grouped in four families; long chain fatty acids, polycyclic aromatic hydrocarbons, linear alkylbenzene sulphonates and organic acids. For the organic acids, there is no effect due to the biomass concentration variation, therefore it is a competitive inhibition; but that doesn't happen with the remaining compounds, where there is a dependence on the complexity of their structure, becoming a non-competitive inhibition. In addition, it was observed that the degradation kinetics is affected, whether diminishing the methane production (polycyclic aromatic hydrocarbons, linear alkylbenzene sulphonates, organics acids) or increasing the initial latency time (long chain fatty acids) without this becoming an obstacle to obtain the maximum methane productions for the latter ones.

  16. Toxicity and repellency of compounds from clove (Syzygium aromaticum) to red imported fire ants Solenopsis invicta (Hymenoptera: Formicidae). (United States)

    Kafle, Lekhnath; Shih, Cheng Jen


    The toxicity and repellency of the bioactive chemicals of clove (Syzygium aromaticum) powder, eugenol, eugenol acetate, and beta-caryophyllene were evaluated against workers of the red imported fire ant, Solenopsis invicta Buren. Clove powder applied at 3 and 12 mg/cm2 provided 100% ant mortality within 6 h, and repelled 99% within 3 h. Eugenol was the fastest acting compound against red imported fire ant compared with eugenol acetate, beta-caryophyllene, and clove oil. The LT50 values inclined exponentially with the increase in the application rate of the chemical compounds tested. However, repellency did not increase with the increase in the application rate of the chemical compounds tested, but did with the increase in exposure time. Eugenol, eugenol acetate, as well as beta-caryophyllene and clove oil may provide another tool for red imported fire ant integrated pest management, particularly in situations where conventional insecticides are inappropriate.

  17. Bioassay standardization for the detection of allelopathic compounds and environmental toxicants using lettuce

    Directory of Open Access Journals (Sweden)

    Mateus Salomão Simões


    Full Text Available The purpose of this study was to assess different experimental conditions to determine a protocol for bioassays based on seed germination and early seedling growth using lettuce (Lactuca sativa L. cv. Grand Rapids as indicator species. This protocol aims to provide support for the standardization of assays of various chemicals such as allelochemicals and environmental toxicants. The following tests were performed: time of germination, temperature, light, solution volume and Petri dish size. For each test (except for time of germination, the influence of the conditions investigated was determined by the endpoints germination percentage, germination speed index, root length, seedling fresh weight and total dry weight. The results showed that variations in the methods altered the results. It is recommended that bioassays using L. sativa L. cv. Grand Rapids be carried out for a minimum period of four days for assessments of both germination and initial growth and that the experimental conditions include a temperature of 20°C, 90-mm Petri dishes or larger, 0.1 mL cypsela solution, and continuous light or 12-hour photoperiod.

  18. Effect of the waste products storage on the environmental pollution by toxic organic compounds

    Directory of Open Access Journals (Sweden)

    Aleksandra Lewkiewicz-Małysa


    Full Text Available A permanent deposition of industrial wastes is a method of its neutralization. A storage yard for toxic materials must meet specific site and construction conditions. The storage place region of toxic organic waste materials has to be monitored. The environmental impact of this waste on the groundwater quality, especially the migration of persistent organic pollutants, was discussed on the example of a chemical plant.

  19. Choose Your Weaponry: Selective Storage of a Single Toxic Compound, Latrunculin A, by Closely Related Nudibranch Molluscs.

    Directory of Open Access Journals (Sweden)

    Karen L Cheney

    Full Text Available Natural products play an invaluable role as a starting point in the drug discovery process, and plants and animals use many interesting biologically active natural products as a chemical defense mechanism against predators. Among marine organisms, many nudibranch gastropods are known to derive defensive metabolites from the sponges they eat. Here we investigated the putative sequestration of the toxic compound latrunculin A--a 16-membered macrolide that prevents actin polymerization within cellular processes--which has been identified from sponge sources, by five closely related nudibranch molluscs of the genus Chromodoris. Only latrunculin A was present in the rim of the mantle of these species, where storage reservoirs containing secondary metabolites are located, whilst a variety of secondary metabolites were found in their viscera. The species studied thus selectively accumulate latrunculin A in the part of the mantle that is more exposed to potential predators. This study also demonstrates that latrunculin-containing sponges are not their sole food source. Latrunculin A was found to be several times more potent than other compounds present in these species of nudibranchs when tested by in vitro and in vivo toxicity assays. Anti-feedant assays also indicated that latrunculin A was unpalatable to rock pool shrimps, in a dose-dependent manner. These findings led us to propose that this group of nudibranchs has evolved means both to protect themselves from the toxicity of latrunculin A, and to accumulate this compound in the mantle rim for defensive purposes. The precise mechanism by which the nudibranchs sequester such a potent compound from sponges without disrupting their own key physiological processes is unclear, but this work paves the way for future studies in this direction. Finally, the possible occurrence of both visual and chemosensory Müllerian mimicry in the studied species is discussed.

  20. Toxic compounds emission from fossil fuels in compression with alternative energies

    Energy Technology Data Exchange (ETDEWEB)

    Halek, F.; Kavousi, A. [Dept. of Energy (Iran). Materials and Energy Resesarch Center


    Transportation sources are one of the leading contributors to hazardous air pollutants. The internal combustion engine emits a large percentage of pollutants, but gasoline and diesel in the liquid form also contribute chemical pollution in the form of vaporization of the fuel as it heats and cools within the gas tank. Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounts made up of two or more fused benzene rings in linear, angular or cluster arrangements. PAHs are considered highly toxic for human beings and several of these compounts are carcinogenic, mutagenic or teratogenic. A major source of PAH in Tehran is related to traffic and the number of gasoline and diesel vehicles. During nearly a 1-year period (throughout 2005) a comprehensive study was done in the Tehran area in 21 stations. Results of PAHs analysis indicated that existence of several low molecular weights, like Fluoranthene, Fluorene and Phenantherene confirm the role of diesel oil emissions in Tehran's atmosphere. Biodiesel, a renewable energy source, is the name for a variety of ester-based oxygenated fuels (11% oxygen by weight) made from vegetable oils: sunflower, safflower, soybean, palm, cottonseed, rapeseed or peanut. The lifecycle production and use of biodiesel produces approximately 80% less carbon dioxide emissions, and almost 100% less sulfur dioxide. Combustion of biodiesel alone provides over a 90% reduction in total unburned hydrocarbons, and a 75-90% reduction in aromatic hydrocarbons. Biodiesel further provides significant reductions in particulates and carbon monoxide than petroleum diesel fuel. Based on mutagenicity tests, biodiesel provides a 90% reduction in cancer risks.

  1. Preparation of acrylic acid-modified chitin improved by an experimental design and its application in absorbing toxic organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chao-Ming, E-mail: [Department of Materials Engineering, Kun Shan University, Tainan, Taiwan (China); Chen, Lung-Chuan, E-mail: [Department of Materials Engineering, Kun Shan University, Tainan, Taiwan (China); Yang, Hui-Chia, E-mail: [Department of Environmental Engineering, Kun Shan University, Tainan, Taiwan (China); Li, Min-Hsing, E-mail: [Department of Environmental Engineering, Kun Shan University, Tainan, Taiwan (China); Pan, Ting-Chung, E-mail: [Department of Environmental Engineering, Kun Shan University, Tainan, Taiwan (China)


    Highlights: Black-Right-Pointing-Pointer Acrylic acid-modified chitin. Black-Right-Pointing-Pointer Experimental design. Black-Right-Pointing-Pointer Graft copolymerization. Black-Right-Pointing-Pointer Adsorption of toxic organic compounds. Black-Right-Pointing-Pointer Very high adsorption capacity. - Abstract: Chitin grafted poly (acrylic acid) (chi-g-PAA) is synthesized and characterized as an adsorbent of toxic organic compounds. Chi-g-PAA copolymers are prepared using of ammonium cerium (IV) nitrate (Ce{sup 4+}) as the initiator. The highest grafting percentage of AA in chitin obtained using the traditional technique is 163.1%. A maximum grafting percentage of 230.6% is obtained using central composite design (CCD). Experimental results are consistent with theoretical calculations. The grafted copolymer is characterized by Fourier transform Infrared spectroscopy and solid state {sup 13}C NMR. A representative chi-g-AA copolymer is hydrolyzed to a type of sodium salt (chi-g-PANa) and used in the adsorption of malachite green (MG), methyl violet (MV), and paraquat (PQ) in aqueous. The monolayer adsorption capacities of these substances are 285.7, 357.1, and 322.6 mg/g-adsorbent, respectively. Thermodynamic calculations show that the adsorption of MG, MV, and PQ are more favored at diluted solutions. The high adsorption capacity of chi-g-PANa for toxic matter indicates its potential in the treatment of wastewater and emergency treatment of PQ-poisoned patients.

  2. Elucidating the mechanisms of nickel compound uptake: A review of particulate and nano-nickel endocytosis and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Muñoz, Alexandra; Costa, Max, E-mail:


    Nickel (Ni) is a worldwide pollutant and contaminant that humans are exposed to through various avenues resulting in multiple toxic responses — most alarming is its clear carcinogenic nature. A variety of particulate Ni compounds persist in the environment and can be distinguished by characteristics such as solubility, structure, and surface charge. These characteristics influence cellular uptake and toxicity. Some particulate forms of Ni are carcinogenic and are directly and rapidly endocytized by cells. A series of studies conducted in the 1980s observed this process, and we have reanalyzed the results of these studies to help elucidate the molecular mechanism of particulate Ni uptake. Originally the process of uptake observed was described as phagocytosis, however in the context of recent research we hypothesize that the process is macropinocytosis and/or clathrin mediated endocytosis. Primary considerations in determining the route of uptake here include calcium dependence, particle size, and inhibition through temperature and pharmacological approaches. Particle characteristics that influenced uptake include size, charge, surface characteristics, and structure. This discussion is relevant in the context of nanoparticle studies and the emerging interest in nano-nickel (nano-Ni), where toxicity assessments require a clear understanding of the parameters of particulate uptake and where establishment of such parameters is often obscured through inconsistencies across experimental systems. In this regard, this review aims to carefully document one system (particulate nickel compound uptake) and characterize its properties.

  3. Toxicity assessment of heavy metals and organic compounds using CellSense biosensor with E.coli

    Institute of Scientific and Technical Information of China (English)

    Hong Wang; Xue Jiang Wang; Jian Fu Zhao; Ling Chen


    A new strategy using an amperometric biosensor with Escherichia coli(E.coli)that provides a rapid toxicity determination of chemical compounds is described.The CellSense biosensor system comprises a biological component immobilized in intimate contact with a transducer which converts the biochemical signal into a quantifiable electrical signal.Toxicity assessment of heavy metals using E.coli biosensors could be finished within 30 min and the 50% effective concentrations(EC50)values of four heavy metals were determined.The results shows that inhibitory effects of four heavy metals to E.coli can be ranked in a decreasing order of Hg2+>Cu2+>Zn2+>Ni2+,which accords to the results of conventional bacterial counting method.The toxicity test of organic compounds by using CellSense biosensor was also demonstrated.The CellSense biosensor with E.coli shows a good,reproducible behavior and can be used for reproducible measurements.

  4. A category approach to predicting the developmental (neuro) toxicity of organotin compounds: the value of the zebrafish (Danio rerio) embryotoxicity test (ZET). (United States)

    Beker van Woudenberg, Anna; Wolterbeek, André; Te Brake, Lindsey; Snel, Cor; Menke, Aswin; Rubingh, Carina; de Groot, Didima; Kroese, Dinant


    Zebrafish embryos were exposed to different organotin compounds during very early development (embryotoxic compound at all time points and endpoints studied. In fact, we observed a clear concordance between the effects observed in our zebrafish embryo model, and those observed with these compounds in full rodent in vivo studies. All organotin compounds classified as developmental (neuro) toxicants in vivo, were correctly classified in the present assay. Together, our results support the ZET model as a valuable tool for providing biological verification for a grouping and a read-across approach to developmental (neuro) toxicity.

  5. Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients

    NARCIS (Netherlands)

    Brand, W.; Schutte, M.E.; Bladeren, van P.J.; Rietjens, I.M.C.M.


    The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be high

  6. Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients

    NARCIS (Netherlands)

    Brand, W.; Schutte, M.E.; Bladeren, van P.J.; Rietjens, I.M.C.M.


    The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be high

  7. Chronic toxicity of polycyclic aromatic compounds to the springtail Folsomia candida and the enchytraeid Enchytraeus cripticus.

    NARCIS (Netherlands)

    Droge, S.T.J.; Leon, M.; Bleeker, E.A.J.; Kraak, M.H.S.; van Gestel, C.A.M.


    Abstract-An urgent need exists for incorporating heterocyclic compounds and (bio)transformation products in ecotoxicological test schemes and risk assessment of polycyclic aromatic compounds (PACs). The aim of the present study therefore was to determine the chronic effects of (heterocyclic) PACs on

  8. Toxic Volatile Organic Compounds (VOCs in the Atmospheric Environment: Regulatory Aspects and Monitoring in Japan and Korea

    Directory of Open Access Journals (Sweden)

    Wen-Tien Tsai


    Full Text Available In the past decades, hazardous air pollutants (HAPs, so-called air toxics or toxic air pollutants, have been detected in the atmospheric air at low concentration levels, causing public concern about the adverse effect of long-term exposure to HAPs on human health. Most HAPs belong to volatile organic compounds (VOCs. More seriously, most of them are known carcinogens or probably carcinogenic to humans. The objectives of this paper were to report the regulatory aspects and environmental monitoring management of toxic VOCs designated by Japan and Korea under the Air Pollution Control Act, and the Clean Air Conservation Act, respectively. It can be found that the environmental quality standards and environmental monitoring of priority VOCs (i.e., benzene, trichloroethylene, tetrachloroethylene, and dichloromethane have been set and taken by the state and local governments of Japan since the early 2000, but not completely established in Korea. On the other hand, the significant progress in reducing the emissions of some toxic VOCs, including acrylonitrile, benzene, 1,3-butadiene, 1,2-dichloroethane, dichloromethane, chloroform, tetrachloroethylene, and trichloroethylene in Japan was also described as a case study in the brief report paper.

  9. Toxic Volatile Organic Compounds in Environmental Tobacco Smoke:Emission Factors for Modeling Exposures of California Populations

    Energy Technology Data Exchange (ETDEWEB)

    Daisey, J.M.; Mahanama, K.R.R.; Hodgson, A.T.


    The primary objective of this study was to measure emission factors for selected toxic air in environmental tobacco smoke (ETS) using a room-sized environmental chamber. The emissions of 23 volatile organic compounds (VOCs), including 1,3-butadiene, three aldehydes and two vapor-phase N-nitrosarnines were determined for six commercial brands of cigarettes and reference cigarette 1R4F. The commercial brands were selected to represent 62.5% of the cigarettes smoked in California. For each brand, three cigarettes were machine smoked in the chamber. The experiments were conducted over four hours to investigate the effects of aging. Emission factors of the target compounds were also determined for sidestream smoke (SS). For almost all target compounds, the ETS emission factors were significantly higher than the corresponding SS values probably due to less favorable combustion conditions and wall losses in the SS apparatus. Where valid comparisons could be made, the ETS emission factors were generally in good agreement with the literature. Therefore, the ETS emission factors, rather than the SS values, are recommended for use in models to estimate population exposures from this source. The variabilities in the emission factors (pgkigarette) of the selected toxic air contaminants among brands, expressed as coefficients of variation, were 16 to 29%. Therefore, emissions among brands were generally similar. Differences among brands were related to the smoked lengths of the cigarettes and the masses of consumed tobacco. Mentholation and whether a cigarette was classified as light or regular did not significantly affect emissions. Aging was determined not to be a significant factor for the target compounds. There were, however, deposition losses of the less volatile compounds to chamber surfaces.

  10. [Elimination of toxic compounds, biological evaluation and partial characterization of the protein from jojoba meal (Simmondsia chinensis [Link] Schneider]. (United States)

    Medina Juárez, L A; Trejo González, A


    The purpose of this study was to establish a new methodology to remove the toxic compounds present in jojoba meal and flour. Also, to perform the biological evaluation of the detoxified products and to chemically characterize the protein fractions. Jojoba meal and seed without testa were deffated with hexane and detoxified with a 7:3 isopropanol-water mixture which removed 86% of total phenolic compounds and 100% of simmondsins originally present, the resulting products had reduced bitterness and caused no deaths on experimental animals. NPR values obtained for diets containing such products were significantly different from those obtained with the casein control (p less than 0.05). Total protein was made up of three different fractions: the water-soluble fraction was the most abundant (61.8%), followed by the salt-soluble (23.6%), and the alkaline soluble fraction (14.6%). The nitrogen solubility curves showed that the isoelectric point for the water-soluble and salt-soluble fractions was pH 3.0, while that of the alkaline fraction fell in the range of 4.5-5.0. All fractions had a maximum solubility at pH 7.0. The methodology reported here, offers a viable solution to eliminate toxic compounds from jojoba meal or seeds, and upgrades the potential use of products such as animal feed or raw material for the production of protein isolates.

  11. Secondary compounds in floral rewards of toxic rangeland plants: impacts on pollinators. (United States)

    Irwin, Rebecca E; Cook, Daniel; Richardson, Leif L; Manson, Jessamyn S; Gardner, Dale R


    The study of plant secondary chemistry has been essential in understanding plant consumption by herbivores. There is growing evidence that secondary compounds also occur in floral rewards, including nectar and pollen. Many pollinators are generalist nectar and pollen foragers and thus are exposed to an array of secondary compounds in their diet. This review documents secondary compounds in the nectar or pollen of poisonous rangeland plants of the western United States and the effects of these compounds on the behavior, performance, and survival of pollinators. Furthermore, the biochemical, physiological, and behavioral mechanisms by which pollinators cope with secondary compound consumption are discussed, drawing parallels between pollinators and herbivores. Finally, three avenues of future research on floral reward chemistry are proposed. Given that the majority of flowering plants require animals for pollination, understanding how floral reward chemistry affects pollinators has implications for plant reproduction in agricultural and rangeland habitats.

  12. Health risks in international container and bulk cargo transport due to volatile toxic compounds

    DEFF Research Database (Denmark)

    Baur, Xaver; Budnik, Lygia T; Zhao, Zhiwei


    on the toxic substance, its chemical reactivity, concentration, the temperature, the contaminated matrix (goods and packing materials), and the packing density in the transport units. Regulations on declaration and handling dangerous goods are mostly not followed. It is obvious that this hazardous situation...... shown to contain volatile toxic substances above the exposure limit values. Possible exposure to these toxic chemicals may occur not only for the applicators but also the receiver by off gassing from products, packing materials or transport units like containers. A number of intoxications, some...... with lethal outcome, occur not only during the fumigation, but also during freight transport (on bulk carriers and other transport vessels), as well as in the logistic lines during loading and unloading. Risk occupations include dock-workers, seafarers, inspectors, as well as the usually uninformed workers...

  13. Sulfhydryl compounds inhibit the cyto- and geno-toxicity of o-phenylphenol metabolites in CHO-K1 cells. (United States)

    Tayama, S; Nakagawa, Y


    The effects of cysteine and reduced glutathione (GSH) on the genotoxicity of o-phenylphenol (OPP) and its metabolites, phenylhydroquinone (PHQ) and phenylbenzoquinone (PBQ), were examined using the frequency of sister-chromatid exchanges (SCEs) and chromosome aberrations in CHO-K1 cells as parameters. Cytotoxic (cell-progression delay) and cytogenetic effects induced by a 3-h treatment with OPP, PHQ (100 micrograms/ml) or PBQ (50 micrograms/ml) with S9 mix after a 27-h expression time were inhibited by cysteine or GSH (3-10 mM). Materials corresponding to the cysteine or GSH adducts were found by HPLC in each incubation mixture. In the culture without S9 mix, PHQ and PBQ showed severe cytotoxicity since no metaphases could be obtained at doses over 25 and 5 micrograms/ml, respectively, and the sulfhydryl compounds inhibited the toxicity by the formation of adducts with PBQ and by inhibiting the formation of PBQ in the case of PHQ. With PHQ, the sulfhydryl compounds appeared to inhibit autooxidation. However, the sulfhydryl compounds did not inhibit the cytotoxic and cytogenetic effects caused by OPP in the cell mixture without S9 mix, but on the contrary intensified them. No adduct formation was detected in the incubation solution. On the basis of these results, it is considered that electrophilic quinone (PBQ) and/or semiquinone (phenylsemiquinone, PSQ) radicals, capable of binding to nucleophilic small molecules (such as cysteine and GSH) or (biological) macromolecules, are produced from metabolite PHQ in metabolic oxidation of OPP, and induce cyto- and geno-toxic effects in the cells. The cyto- and geno-toxic effects of OPP itself to the cells are clearly independent of any electrophilic radical reaction.

  14. Biodegradability and aquatic toxicity of quaternary ammonium-based gemini surfactants: Effect of the spacer on their ecological properties. (United States)

    Garcia, M Teresa; Kaczerewska, Olga; Ribosa, Isabel; Brycki, Bogumił; Materna, Paulina; Drgas, Małgorzata


    Aerobic biodegradability and aquatic toxicity of five types of quaternary ammonium-based gemini surfactants have been examined. The effect of the spacer structure and the head group polarity on the ecological properties of a series of dimeric dodecyl ammonium surfactants has been investigated. Standard tests for ready biodegradability assessment (OECD 310) were conducted for C12 alkyl chain gemini surfactants containing oxygen, nitrogen or a benzene ring in the spacer linkage and/or a hydroxyethyl group attached to the nitrogen atom of the head groups. According to the results obtained, the gemini surfactants examined cannot be considered as readily biodegradable compounds. The negligible biotransformation of the gemini surfactants under the standard biodegradation test conditions was found to be due to their toxic effects on the microbial population responsible for aerobic biodegradation. Aquatic toxicity of gemini surfactants was evaluated against Daphnia magna. The acute toxicity values to Daphnia magna, IC50 at 48 h exposure, ranged from 0.6 to 1 mg/L. On the basis of these values, the gemini surfactants tested should be classified as toxic or very toxic to the aquatic environment. However, the dimeric quaternary ammonium-based surfactants examined result to be less toxic than their corresponding monomeric analogs. Nevertheless the aquatic toxicity of these gemini surfactants can be reduced by increasing the molecule hydrophilicity by adding a heteroatom to the spacer or a hydroxyethyl group to the polar head groups.

  15. Biomonitoring of toxic compounds of airborne particulate matter in urban and industriel areas

    DEFF Research Database (Denmark)

    Klumpp, Andreas; Ro-Poulsen, Helge


    The toxicity and ecotoxicity of airborne particulate matter is determined by its physical features, but also by its chemical composition. The standardised exposure of accumulative bioindicator plants is suggested as an efficient and reliable tool to assess and monitor effects of particulate matter...

  16. An imidazoline compound completely counteracts interleukin-1[beta] toxic effects to rat pancreatic islet [beta] cells

    DEFF Research Database (Denmark)

    Papaccio, Gianpaolo; Nicoletti, Ferdinando; Pisanti, Francesco A


    In vitro studies have demonstrated that interleukin (IL)-1beta decreases insulin and DNA contents in pancreatic islet beta cells, causing structural damage, that it is toxic to cultured human islet beta cells and that it is able to induce apoptosis in these cells....


    This Second Edition of the Compendium has been prepared to provide regional, state and local environmental regulatory agencies with step-by-step sampling and analysis procedures for the determination of selected toxic organic pollutants in ambient air. It is designed to assist t...

  18. Short-term toxicity studies with triphenyltin compounds in rats and guinea-pigs

    NARCIS (Netherlands)

    Verschuuren, H.G.; Kroes, R.; Vink, H.H.; Esch, G.J. van


    Short-term toxicity studies have been carried out in rats and guinea-pigs fed diets containing triphenyltin acetate (TPTA), triphenyltin hydroxide (TPTH) or triethyltin hydroxide (TETH) for 90 days at levels ranging from 0 to 50 ppm. The lowest dietary levels found to retard growth in rats and guin

  19. A system for the determination of trace-level polar and non-polar toxic organic compounds in ambient air

    Energy Technology Data Exchange (ETDEWEB)

    Tipler, A.; Dang, R.; Hoberecht, H. [Perkin Elmer Corp., Norwalk, CT (United States). Fresh Aire Lab.


    A gas chromatographic system is described for the determination of toxic organic compounds in ambient air. These compounds include all those specified within the US EPA Compendium Method TO14 and some polar additional analytes under consideration for the proposed TO15 Method. The system supports both on-line and off-line (passivated canisters and adsorption tubes) methods for sampling air--providing a fully automated analysis. A key feature of the system is that liquid cryogen is not required for either the analyte preconcentration or the subsequent chromatographic separation. Water management is achieved by dry-purging an adsorbent trap upon which the sample analytes have been retained. The performance of the system is demonstrated with conventional detection systems (electron capture and flame ionization) and with a mass spectrometer.

  20. Environmental toxicity of effluents of different laboratories of a compounding pharmacy

    Directory of Open Access Journals (Sweden)

    Luciano Henrique Pinto


    Full Text Available There is a growing concern over so-called "emerging pollutants" in the production of pharmaceuticals. These pollutants reach the environment from household waste or from leftovers generated during production. In small concentrations of the order of micrograms per liter or less, or in concentrations ineffective at producing a biological response in humans in the short-term, chronic exposure can still have a great impact on the environment. This study evaluated the possible risk of contamination posed by the release of raw materials from small-scale drug production by compounding pharmacies, based on an ecotoxicity assessment conducted by biomonitoring Euglena gracilis algae. The study also investigated the impacts on behavior and the changes in the photosynthesis process of this algae. Samples of four laboratories with different demands were comparatively analyzed. Behavioral changes of the algae (ascent rate to the surface, r-value and speed of movement were assessed by biomonitoring NG-TOX and photosynthetic parameters were measured by pulse-amplitude modulation fluorometer (PAM. The results showed that the effluent from hormone laboratory that had a low semestral production had little impact. On another hand, the effluent from the psychotropics laboratory, even with intermediate demand, had a significant impact on the behavior and photosynthetic activity of algae. The behavior differences observed between the different sectors of drugs shows that the impacts and potential environmental risks are different for each sector. The demand and the different substances manipulated can be crucial in risk classification and in the choice of decontamination methods.

  1. Matrix-derived combination effects influencing absorption, distribution, metabolism and excretion (ADME) of food-borne toxic compounds: implications for risk assessment

    NARCIS (Netherlands)

    Rietjens, I.; Tyrakowska, B.; Berg, van den S.J.P.L.; Soffers, A.E.M.F.; Punt, A.


    Absorption, distribution, metabolism and excretion (ADME) of food-borne toxic compounds may be influenced by other compounds or constituents present in the food. The present review presents an overview of evidence currently available on food matrix-derived combination effects influencing the ADME ch


    Directory of Open Access Journals (Sweden)

    Natalia N. Gorinchoy


    Full Text Available The electron-conformational (EC method is employed for the toxicophore (Tph identification and quantitative prediction of toxicity using the training set of 24 compounds that are considered as fragrance allergens. The values of a=LD50 in oral exposure of rats were chosen as a measure of toxicity. EC parameters are evaluated on the base of conformational analysis and ab initio electronic structure calculations (including solvent influence. The Tph consists of four sites which in this series of compounds are represented by three carbon and one oxygen atoms, but may be any other atoms that have the same electronic and geometric features within the tolerance limits. The regression model taking into consideration the Tph flexibility, anti-Tph shielding, and influence of out-of-Tph functional groups predicts well the experimental values of toxicity (R2 = 0.93 with a reasonable leaveone- out cross-validation.

  3. Comparative evaluation of short-term toxicity of inorganic arsenic compounds on Artemia salina. (United States)

    GuŢu, Claudia Maria; Olaru, Octavian Tudorel; Purdel, Nicoleta Carmen; Ilie, Mihaela; NeamŢu, Marius Cristian; Dănciulescu Miulescu, Rucsandra; Avramescu, Elena Taina; Margină, Denisa Marilena


    The study aimed to assess the short-term effects exerted by two inorganic arsenic species (arsenite and arsenate) on Artemia salina after 24, 48 and 72 h. The dose-lethality curves obtained indicate that the lethality induced by arsenite was higher than by arsenate. The lowest observed effect concentration for arsenite (0.5 μg/mL) is similar with the no observed effect concentration for arsenate, thus indicating that the toxicity of arsenite is higher compared with arsenate. Also, the lethal concentration 50 values confirm that arsenite induced about 1.24-fold higher toxicity than arsenate at 24 h and about three-fold higher toxicity at 48 h and 72 h of exposure. Both LC50 (lethal concentration 50) values are indicating negligible effects exhibited by arsenic at this trophic level after short-term exposure. The predicted no effect concentration in the surface aquatic compartment corresponds to 10.38 μg/L, similar to the limit imposed by Directive 98/83/EC.

  4. Widespread use of toxic skin lightening compounds: medical and psychosocial aspects. (United States)

    Ladizinski, Barry; Mistry, Nisha; Kundu, Roopal V


    Hyperpigmentation disorders and skin lightening treatments have a significant impact on the dermatologic, physiologic, psychologic, economic, social, and cultural aspects of life. Skin lightening compounds, such as hydroquinone and topical corticosteroids, are often used to treat hyperpigmentation disorders, such as melasma, or lighten skin for cosmetic purposes. Despite their established effectiveness, a multitude of dermatologic and systemic complications have been associated with these agents. Regulatory agencies have also recognized the adverse effects of skin lighteners and many countries around the world now forbid the production and sale of these compounds, although this prohibition has not significantly curtailed distribution. Dermatologists and users of cosmetic products should be aware of the various components in bleaching compounds, their potential adverse effects, and alternative options for skin lightening.

  5. Volatile organic compounds released from Microcystis flos-aquae under nitrogen sources and their toxic effects on Chlorella vulgaris. (United States)

    Xu, Qinghuan; Yang, Lin; Yang, Wangting; Bai, Yan; Hou, Ping; Zhao, Jingxian; Zhou, Lv; Zuo, Zhaojiang


    Eutrophication promotes massive growth of cyanobacteria and algal blooms, which can poison other algae and reduce biodiversity. To investigate the differences in multiple nitrogen (N) sources in eutrophicated water on the emission of volatile organic compounds (VOCs) from cyanobacteria, and their toxic effects on other algal growth, we analyzed VOCs emitted from Microcystis flos-aquae with different types and concentrations of nitrogen, and determined the effects under Normal-N and Non-N conditions on Chlorella vulgaris. M. flos-aquae released 27, 22, 20, 27, 19, 25 and 17 compounds, respectively, with NaNO3, NaNO2, NH4Cl, urea, Ser, Lys and Arg as the sole N source. With the reduction in N amount, the emission of VOCs was increased markedly, and the most VOCs were found under Non-N condition. C. vulgaris cell propagation, photosynthetic pigment and Fv/Fm declined significantly following exposure to M. flos-aquae VOCs under Non-N condition, but not under Normal-N condition. When C. vulgaris cells were treated with two terpenoids, eucalyptol and limonene, the inhibitory effects were enhanced with increasing concentrations. Therefore, multiple N sources in eutrophicated water induce different VOC emissions from cyanobacteria, and reduction in N can cause nutrient competition, which can result in emissions of more VOCs. Those VOCs released from M. flos-aquae cells under Non-N for nutrient competition can inhibit other algal growth. Among those VOCs, eucalyptol and limonene are the major toxic agents.

  6. Glioblastoma Treatment: Bypassing the Toxicity of Platinum Compounds by Using Liposomal Formulation and Increasing Treatment Efficiency With Concomitant Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Charest, Gabriel; Sanche, Leon [Center for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, Sherbrooke, Quebec (Canada); Fortin, David; Mathieu, David [Department of Surgery, Division of Neurosurgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec (Canada); Paquette, Benoit, E-mail: [Center for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, Sherbrooke, Quebec (Canada)


    Purpose: Treatments of glioblastoma with cisplatin or oxaliplatin only marginally improve the overall survival of patients and cause important side effects. To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome. Methods and Materials: In this study, cisplatin, oxaliplatin, carboplatin, Lipoplatin (the liposomal formulation of cisplatin), and Lipoxal (the liposomal formulation of oxaliplatin) were tested on F98 glioma orthotopically implanted in Fischer rats. The platinum compounds were administered by intracarotid infusion and were assessed for the ability to reduce toxicity, improve cancer cell uptake, and increase survival of animals when combined or not combined with radiotherapy. Results: The tumor uptake was 2.4-fold more important for Lipoxal than the liposome-free oxaliplatin. Lipoxal also improved the specificity of oxaliplatin as shown by a higher ratio of tumor to right hemisphere uptake. Surprisingly, Lipoplatin led to lower tumor uptake compared with cisplatin. However, Lipoplatin had the advantage of largely reducing the toxicity of cisplatin and allowed us to capitalize on the anticancer activity of this agent. Conclusion: Among the five platinum compounds tested, carboplatin showed the best increase in survival when combined with radiation for treatment of glioma implanted in Fischer rats.

  7. Alkane-Based Urethane Potting Compounds (United States)

    Morris, D. E.


    New low viscosity urethanes easily mixed, molded, and outgassed. Alkane-based urethanes resist hydrolysis and oxidation and have excellent dielectric properties. Low-viscosity alkane-based urethane prepolymer prepared by one-step reaction of either isophorone diisocyanate or methyl-bis (4-cyclohexyl isocyanate) with hydrogenated, hydroxy-terminated polybutadiene (HTPBD).

  8. The influence of spin-labeled fluorene compounds on the assembly and toxicity of the aβ peptide.

    Directory of Open Access Journals (Sweden)

    Jitka Petrlova

    Full Text Available BACKGROUND: The deposition and oligomerization of amyloid β (Aβ peptide plays a key role in the pathogenesis of Alzheimer's disease (AD. Aβ peptide arises from cleavage of the membrane-associated domain of the amyloid precursor protein (APP by β and γ secretases. Several lines of evidence point to the soluble Aβ oligomer (AβO as the primary neurotoxic species in the etiology of AD. Recently, we have demonstrated that a class of fluorene molecules specifically disrupts the AβO species. METHODOLOGY/PRINCIPAL FINDINGS: To achieve a better understanding of the mechanism of action of this disruptive ability, we extend the application of electron paramagnetic resonance (EPR spectroscopy of site-directed spin labels in the Aβ peptide to investigate the binding and influence of fluorene compounds on AβO structure and dynamics. In addition, we have synthesized a spin-labeled fluorene (SLF containing a pyrroline nitroxide group that provides both increased cell protection against AβO toxicity and a route to directly observe the binding of the fluorene to the AβO assembly. We also evaluate the ability of fluorenes to target multiple pathological processes involved in the neurodegenerative cascade, such as their ability to block AβO toxicity, scavenge free radicals and diminish the formation of intracellular AβO species. CONCLUSIONS: Fluorene modified with pyrroline nitroxide may be especially useful in counteracting Aβ peptide toxicity, because they possess both antioxidant properties and the ability to disrupt AβO species.

  9. Comparison of extracts and toxicities of organic compounds in drinking water concentrated by single and composite XAD resins. (United States)

    Zhou, Xue; Xiang, Lunhui; Wu, Fenghong; Peng, Xiaoling; Xie, Hong; Wang, Jiachun; Yang, Kedi; Lu, Wenqing; Wu, Zhigang


    We compared extracts and toxicities of organic compounds (OCs) in drinking water concentrated by composite XAD-2/8 resin (mixed with an equal volume of XAD-2 and XAD-8 resins) with those extracted by single XAD-2 (non-polar) and XAD-8 (polar) resins. Drinking water was processed from raw water of the Han River and the Yangtze River in Wuhan section, China. The extraction efficiency of all resins was controlled at 30%. The types of extracted OCs were detected by gas chromatography-mass spectrometry, and the cytotoxicity and genotoxicity were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and comet assays, respectively, in human hepatoma HepG2 cells. Our results showed that XAD-2/8 extracted a larger variety of OCs, compared with XAD-8 and XAD-2. The cytotoxicity and genotoxicity of extracted OCs were in the order of XAD-8> XAD-2/8> XAD-2 at almost all tested concentrations after 24 h treatment (P < 0.05). Our findings suggest that single XAD resin selectively extracts either polar or non-polar OCs, which would lead to over- or under-estimation of the toxicity of drinking water. Nevertheless, composite resin extracts both polar and non-polar OCs, and could be utilized as a useful extraction technique to evaluate the level and toxicity of OCs in drinking water.

  10. 基于偏最小二乘法的乌头碱类化合物毒性的定量构效关系研究%Study on the quantitative structure-toxicity relationships of aconitine compounds basing on partial least squares method

    Institute of Scientific and Technical Information of China (English)

    李佐静; 王琳; 闫心丽; 高志祥; 孟繁浩


    乌头碱类化合物属于二萜类生物碱,存在于乌头属欧乌头、川乌、北草乌和华乌头等多种毛茛科植物中,该类化合物既是其活性成分,也是其毒性成分。利用化合物定量结构-毒性效应关系(QSTR)方法研究了14个乌头碱类化合物的各种量化参数对其毒性的影响,并建立了毒性预测模型。由于该类化合物是从中药中提取分离的生物碱,样本数量相对较少,本文采用了偏最小二乘回归方法(PLS)进行降维,进行4个成分的提取及建模。毒性预测模型为:Log(toxi)=0.1593*Mass+0.2908*LogP+1.5475*SAA-0.5222*SAG-0.6104*Volume+0.3112*Ref+0.1784*Polar+0.1785*BE+0.1634*HF-0.1387*Dipole+0.1412,结果表明该模型具有较好的毒性预测能力。%Aconitine compounds are found in Aconitum Ouwu head, Chuan Wu, Aconitum, and the North China and other Ranunculaceae Aconitum plants, which are not only the active ingredient but also the toxic component. The quantum chemistry parameters of 14 kinds of aconitine compounds were studied using the quantitative structure toxicity relationships (QSTR) method to affect its toxicity and to build the forecast model. In this paper, Partial least squares method was taken into account to reduce the dimension and build the model using 4 principle components because of the limitation of sample space. It is tested that the model has a good forecasting ability. The model is: Log(toxi)=0.1593*Mass+0.2908*LogPf 1.5475*SAA-0.5222*SAG-0.6104*Volume+0.3112*Ref+0.1784*Polar+0.1785*BE+0.1634*HF-0.1387*Dipole+0.1412.

  11. Carbon-Based Compounds and Exobiology (United States)

    Kerridge, John; DesMarais, David; Khanna, R. K.; Mancinelli, Rocco; McDonald, Gene; diBrozollo, Fillipo Radicati; Wdowiak, Tom


    The Committee for Planetary and Lunar Explorations (COMPLEX) posed questions related to exobiological exploration of Mars and the possibility of a population of carbonaceous materials in cometary nuclei to be addressed by future space missions. The scientific objectives for such missions are translated into a series of measurements and/or observations to be performed by Martian landers. These are: (1) A detailed mineralogical, chemical, and textural assessment of rock diversity at a landing site; (2) Chemical characterization of the materials at a local site; (3) Abundance of Hydrogen at any accessible sites; (4) Identification of specific minerals that would be diagnostic of aqueous processes; (5) Textual examination of lithologies thought to be formed by aqueous activity; (6) Search for minerals that might have been produced as a result of biological processes; (7) Mapping the distribution, in three dimensions, of the oxidant(s) identified on the Martian surface by the Viking mission; (8) Definition of the local chemical environment; (9) Determination of stable-isotopic ratios for the biogenic elements in surface mineral deposits; (10) Quantitative analysis of organic (non-carbonate) carbon; (11) Elemental and isotopic composition of bulk organic material; (12) Search for specific organic compounds that would yield information about synthetic mechanisms, in the case of prebiotic evolution, and about possible bio-markers, in the case of extinct or extant life; (13) and Coring, sampling, and detection of entrained gases and cosmic-ray induced reaction products at the polar ice cap. A discussion of measurements and/or observations required for cometary landers is included as well.

  12. Effects of Electron Acceptors, Reducing Agents, and Toxic Metabolites on Anaerobic Degradation of Heterocyclic Compounds

    DEFF Research Database (Denmark)

    Licht, Dorthe; Ahring, Birgitte Kiær; Arvin, Erik


    Degradation of four heterocyclic compounds was examined under nitrate-reducing, sulphate-reducing and methanogenic conditions. Soil samples from a creosote-polluted site in Denmark were used as inoculum. Indole and quinoline were degraded under all redox conditions with the highest degradation...

  13. Novel squamosamide derivative (compound FLZ) attenuates Aβ25-35-induced toxicity in SH-SY5Y cells

    Institute of Scientific and Technical Information of China (English)

    Fang FANG; Geng-tao LIU


    Aim: The aim of the present study was to investigate the protective effect of compound N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide (compound FLZ), a novel synthetic ana-logue of nature squamosamide, on Aβ25-35-induced toxicity and its active mecha-nism in human neuroblastoma SH-SY5Y cells. Methods: SH-SY5Y cells were pre-incubated with various concentrations of compound FLZ for 30 min and then cultivated with Aβ25-35 (25 μmol/L) for 48 h to induce neurotoxicity. Cell viability, lactate dehydrogenase (LDH) release, and the glutathione (GSH) level were deter-mined by a biochemical analysis. The cell apoptotic ratio and intracellular reactive oxygen species (ROS) level were measured by a flow cytometry analysis. The expression of apoptosis protein (Bcl-2 and Bax) and cytochrome c release were assayed by the Western blot method. Results: The pretreatment of SH-SY5Y cells with FLZ (1 and 10 μmol/L) markedly increased cell viability and decreased LDH release and morphological injury. Also, FLZ attenuated the Aβ25-35-induced apoptotic cell ratio, regulated the apoptosis protein (Bcl-2 and Bax) expression, and decreased the cytochrome c release from mitochondria. FLZ also signifi-cantly inhibited the generation of ROS and the depletion of GSH induced by Aβ25-35 in SH-SY5Y cells. Conclusion: FLZ has protective action against Aβ25-35-in-duced toxicity in SH-SY5Y cells, which might be mediated through its antioxi-dant property.


    Institute of Scientific and Technical Information of China (English)

    Yao Jianchu; Zhou Ji; Yu Jun


    A concept of an intelligent optimal design approach is proposed, which is organized by a kind of compound knowledge model. The compound knowledge consists of modularized quantitative knowledge, inclusive experience knowledge and case-based sample knowledge. By using this compound knowledge model, the abundant quantity information of mathematical programming and the symbolic knowledge of artificial intelligence can be united together in this model. The intelligent optimal design model based on such a compound knowledge and the automatically generated decomposition principles based on it are also presented. Practically, it is applied to the production planning, process schedule and optimization of production process of a refining & chemical work and a great profit is achieved. Specially, the methods and principles are adaptable not only to continuous process industry, but also to discrete manufacturing one.


    Institute of Scientific and Technical Information of China (English)


    With the development of modern agriculture,envi-ronmental contamination by a variety of organic toxicagents has been detected in many freshwater systems.These include herbicides,insecticides,surfactants andother organic compounds,which have,been reported byStratton[1]and many other authors to affect boththeir tar-get and non-target organisms whenever dischargedintotheenvironment,thus impairing heavily on the structure andfunction of ecosystems.Therefore,it is necessary to de-velop pesticides which are highl...

  16. Effects of sludge retention time (SRT) and biosurfactant on the removal of polyaromatic compounds and toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Sponza, Delia Teresa, E-mail: [Dokuz Eylul University, Engineering Faculty, Environmental Engineering Department, Buca Kaynaklar Campus, 35160 Izmir (Turkey); Gok, Oguzhan [Dokuz Eylul University, Engineering Faculty, Environmental Engineering Department, Buca Kaynaklar Campus, 35160 Izmir (Turkey)


    Graphical abstract: Acute toxicities in (a) influent wastewater (EC{sub 50} = 45.02 ng ml{sup -1}) and (b) effluent wastewater in aerobic activated sludge reactor at SRT = 25 days (EC{sub 6} = 5.30 ng ml{sup -1}). Highlights: Black-Right-Pointing-Pointer Over 90% of the total PAHs was removed at Rhamnolipid and sludge retention time of 15 mg l{sup -1} and 25 days. Black-Right-Pointing-Pointer 93% of the COD originating from the inert organics was removed in the aerobic reactor. 96-97% of the Rhamnolipid was biodegraded. Black-Right-Pointing-Pointer The EC50 value was reduced from EC{sub 50} = 45.02 ng ml{sup -1} to C{sub 6} = 5.30 ng ml{sup -1} with Daphnia magna. Toxicity removals originating from the PAHs were 96%. - Abstract: A laboratory-scale aerobic activated sludge reactor (AASR) system was employed to investigate the effects of SRT on the removal of three less hydrophobic and six more hydrophobic PAHs in the presence of rhamnolipid (RD), emulsan (EM) and surfactine (SR) biosurfactants. Among the biosurfactants it was found that RD exhibits a better performance than the others in the removal of PAHs. At a RD of 15 mg l{sup -1} aerobic treatment for 25 days SRT was enough to remove over 90% of the total PAHs, 88% of the COD originating from the inert organics (COD{sub inert}) and 93% of the COD originating from the inert soluble microbial products (COD{sub imp}). At this SRT and RD concentration, about 96-98% of the RD was biodegraded by the AASR system, 1.2-1.4% was accumulated in the system, 1.1-1.3% was released in the effluent, and 1.2-1.4% remained in the waste sludge. The addition of electron acceptors (NO{sub 3}{sup -1}, SO{sub 4}{sup -2}) and increasing of temperature up to 45 Degree-Sign C enhanced the PAH yields. The most effective PAH degradation occurred in high-oxygenated and neutral pH conditions. The PAH concentration affecting half of the Daphnia magna organism (EC{sub 50} value) was reduced from EC{sub 50} = 45.02 ng ml{sup -1} to the PAH

  17. Integrated scientific data bases review on asulacrine and associated toxicity. (United States)

    Afzal, Attia; Sarfraz, Muhammad; Wu, Zimei; Wang, Guangji; Sun, Jianguo


    Asulacrine (ASL), a weakly basic and highly lipophilic drug was synthesized in 1980's in cancer research laboratory of Auckland by modifications to the acridine portion of amsacrine on 3-, 4- and 5-substitution patterns. In contrast to its precursor amsacrine (m-AMSA), ASL was effective not only against leukemia and Lewis lung tumor system but also a wide variety of solid tumor. Its metabolic pathway is not same to amsacrine hence different side effects, hepatotoxicity and excretion was observed. Asulacrine is under phase II clinical trials and has showed promising results but its toxicity especially phlebitis is stumbling block in its clinical implementation. This review is an effort to give a possible clue, based on scientifically proven results, to the researchers to solve the mystery of associated toxicity, phlebitis. Review covers the available literature on asulacrine and other acridine derivatives regarding pharmacology, pharmacokinetics, quantitative structure activity relationship and toxicology via electronic search using scientific databases like PubMed and others. To date, all abstracts and full-text articles were discussed and analyzed. The tabulated comparisons and circuitry mechanism of ASL are the added features of the review which give a complete understanding of hidden aspects of possible route cause of associated toxicity, the phlebitis.

  18. Toxicity of a plant based mosquito repellent/killer. (United States)

    Singh, Bhoopendra; Singh, Prakash Raj; Mohanty, Manoj Kumar


    The mission to make humans less attractive to mosquitoes has fuelled decades of scientific research on mosquito behaviour and control. The search for the perfect topical insect repellent/killer continues. This analysis was conducted to review and explore the scientific information on toxicity produced by the ingredients/contents of a herbal product. In this process of systemic review the following methodology was applied. By doing a MEDLINE search with key words of selected plants, plant based insect repellents/killers pertinent articles published in journals and authentic books were reviewed. The World Wide Web and the Extension Toxicity Network database (IPCS-ITOX) were also searched for toxicology data and other pertinent information. Repellents do not all share a single mode of action and surprisingly little is known about how repellents act on their target insects. Moreover, different mosquito species may react differently to the same repellent. After analysis of available data and information on the ingredient, of the product in relation to medicinal uses, acute and chronic toxicity of the selected medicinal plants, it can be concluded that the ingredients included in the herbal product can be used as active agents against mosquitoes. If the product which contains the powder of the above said plants is applied with care and safety, it is suitable fo use as a mosquito repellent/killer.

  19. Wildlife toxicity extrapolations: Allometry versus physiologically-based toxicokinetics

    Energy Technology Data Exchange (ETDEWEB)

    Fairbrother, A. [Ecological Planning and Toxicology Inc., Corvallis, OR (United States); Berg, M. van den [Univ. of Utrecht (Netherlands). Research Inst. of Toxicology


    Ecotoxicological assessments must rely on the extrapolation of toxicity data from a few indicator species to many species of concern. Data are available from laboratory studies (e.g., quail, mallards, rainbow trout, fathead minnow) and some planned or serendipitous field studies of a broader, but by no means comprehensive, suite of species. Yet all ecological risk assessments begin with an estimate of risk based on information gleaned from the literature. The authors are then confronted with the necessity of extrapolating toxicity information from a limited number of indicator species to all organisms of interest. This is a particularly acute problem when trying to estimate hazards to wildlife in terrestrial systems as there is an extreme paucity of data for most chemicals in all but a handful of species. The question arises of how interspecific extrapolations should be made. Should extrapolations be limited to animals within the same class, order, family or genus? Alteratively, should extrapolations be made along trophic levels or physiologic similarities rather than by taxonomic classification? In other words, is an avian carnivore more like a mammalian carnivore or an avian granivore in its response to a toxic substance? Can general rules be set or does the type of extrapolation depend upon the class of chemical and its mode of uptake and toxicologic effect?

  20. Subchronic toxicity of chlorine dioxide and related compounds in drinking water in the nonhuman primate. (United States)

    Bercz, J P; Jones, L; Garner, L; Murray, D; Ludwig, D A; Boston, J


    Subchronic toxicities of ClO2, NaClO2, NaClO3 and NH2Cl were studied in the African Green monkeys (Cercopithecus aethiops). The chemicals were administered in drinking water during 30-60 days subchronic rising dose protocols. The only unexpected and significant toxic effect was elicited by ClO2; this chemical inhibited thyroid metabolism in the animals at a dose of ca. 9.0 mg/kg/day. A statistically significant decrease of serum thyroxine occurred after the fourth week of exposure to 100 mg/l.concentration. The extent of thyroid suppression was dose dependent in each individual monkey, and was reversible after cessation of exposure. NaClO2 and NaClO3 failed to elicit similar effects in doses up to ca. 60 mg/kg/day. Also, NaClO4 or NH2Cl did not cause T-4 suppression in doses of 10 mg/kg/day. The selective thyroid effect of ClO2 was unexplained and it appeared to be paradoxical since ClO2 was rapidly reduced by the oral and gastric secretions to nonoxidizing species (presumably Cl-). No evidence of thyroid effects were detected in the serum of human volunteers who ingested approximately 1 mg/l. of ClO2 in drinking water as a result of routine use in the community water treatment process. Sodium chlorite induced dose-dependent oxidative stress on hematopoesis, causing decreased hemoglobin and red cell count and increased methemoglobin content. At the same time, serum transaminase (SGPT) levels showed significant subclinical elevation. The hematologic effects of NaClO2 rebounded during exposure indicating compensatory hemopoietic activity taking effect during oxidative stress. Sodium chlorate and chloramine did not induce detectable hematologic changes in the animals. PMID:7151767

  1. Toxicity of some bis Mannich bases and corresponding piperidinols in the brine shrimp (Artemia salina) bioassay. (United States)

    Gul, H Inci; Gul, Mustafa; Erciyas, Ercin


    Some acetophenone-derived bis Mannich bases were synthesized: bis[beta-benzoylethyl]ethylamine hydrochloride (IIa), bis[beta-(p-methylbenzoyl)ethyl]ethylamine hydrochloride (IIb), bis[beta-(p-chlorobenzoyl)ethyl]ethy- lamine hydrochloride (IId), bis[(2-thienylcarbonyl)ethyl]ethylamine hydrochloride (IIe); some corresponding piperidinol derivatives: 3-benzoyl-1-ethyl-4-phenyl-4-piperidinol hydrochloride (IIIa), 1-ethyl-3-(p-methyl- benzoyl)-4-(p-methylphenyl)-4-piperidinol hydrochloride (IIIb), 1-ethyl-3-(p-methoxybenzoyl)-4-(p-methoxy- phenyl)-4-piperidinol hydrochloride (IIIc), 1-ethyl-3-(p-chlorobenzoyl)-4-(p-chlorophenyl)-4-piperidinol hydrochloride (IIId), 1-ethyl-4-(2-thienyl)-3-(2-thienylcarbonyl)-4-piperidinol hydrochloride (IIIe); and some representative quaternary piperidinols: 3-benzoyl-1-ethyl-4-hydroxy-1-methyl-4-phenylpiperidinium iodide (IIIf), 1-ethyl-4-hydroxy-1-methyl-3-(p-methylbenzoyl)-4-(p-methylphenyl)piperidinium iodide (IIIg). Toxicity was tested by the brine shrimp bioassay as an intermediate test before further in vivo animal experiments. Piperidine derivatives were found to be more potent than bis Mannich bases. Quaternary piperidine derivatives IIIf and IIIg and also non-quaternary piperidine derivatives IIIb, IIIe, IIIc and IIId were more toxic than 5-fluorouracil in brine shrimp bioassay. Except for IIe, bis Mannich bases were not effective. Quaternization and conversion of bis Mannich bases to corresponding piperidines improved the toxicity. The lipid solubility of the compounds may not affect the toxicity. From these findings the quaternary piperidine derivatives IIIf and IIIg could be used in further drug development and also for in vivo experiments.

  2. The volatile compound BinBase mass spectral database

    Directory of Open Access Journals (Sweden)

    Barupal Dinesh K


    Full Text Available Abstract Background Volatile compounds comprise diverse chemical groups with wide-ranging sources and functions. These compounds originate from major pathways of secondary metabolism in many organisms and play essential roles in chemical ecology in both plant and animal kingdoms. In past decades, sampling methods and instrumentation for the analysis of complex volatile mixtures have improved; however, design and implementation of database tools to process and store the complex datasets have lagged behind. Description The volatile compound BinBase (vocBinBase is an automated peak annotation and database system developed for the analysis of GC-TOF-MS data derived from complex volatile mixtures. The vocBinBase DB is an extension of the previously reported metabolite BinBase software developed to track and identify derivatized metabolites. The BinBase algorithm uses deconvoluted spectra and peak metadata (retention index, unique ion, spectral similarity, peak signal-to-noise ratio, and peak purity from the Leco ChromaTOF software, and annotates peaks using a multi-tiered filtering system with stringent thresholds. The vocBinBase algorithm assigns the identity of compounds existing in the database. Volatile compound assignments are supported by the Adams mass spectral-retention index library, which contains over 2,000 plant-derived volatile compounds. Novel molecules that are not found within vocBinBase are automatically added using strict mass spectral and experimental criteria. Users obtain fully annotated data sheets with quantitative information for all volatile compounds for studies that may consist of thousands of chromatograms. The vocBinBase database may also be queried across different studies, comprising currently 1,537 unique mass spectra generated from 1.7 million deconvoluted mass spectra of 3,435 samples (18 species. Mass spectra with retention indices and volatile profiles are available as free download under the CC-BY agreement (http

  3. In vitro and in vivo effects of easily administered, low-toxic retinoid and phenylacetate compounds on human neuroblastoma cells. (United States)

    Sidell, N; Pasquali, M; Malkapuram, S; Barua, A B; Wanichkul, T; Wada, R K


    We have investigated the effects of the low-toxic retinoid, all-trans retinoyl beta-glucuronide (RAG) alone and in combination with the phenylacetate (PA) derivative 4-chloro-phenylacetate (4-CPA) on the human neuroblastoma cell line, LA-N-5. In vitro studies demonstrated that RAG and 4-CPA treatments alone showed differentiation-inducing activity on LA-N-5 cells, with 4-CPA found to be about three-fold more potent than the PA parent compound in inducing morphologic differentiation and growth inhibition. As previously reported for retinoic acid (RA) and PA, RAG and 4-CPA were significantly more effective in their antiproliferative effects on the cells than either agent alone. Pharmacologic studies of 4-CPA in mice demonstrated that blood plasma levels reached peak concentrations 4 h after bolus administration of the compound and showed slow clearance characteristics with an apparent half-life of 4-8 h. As opposed to PA, 4-CPA was found to be essentially odourless and readily consumed in drinking water, giving rise to steady-state blood plasma levels of 4-CPA in the near mM range. Continuous consumption of 4-CPA in this manner for up to 5 months demonstrated no apparent adverse effects on the mice. Long-term RAG- and/or 4-CPA-treatment of nude mice injected with LA-N-5 cells demonstrated that both compounds alone exhibit potent antitumour activity. Together, RAG plus 4-CPA was the most effective treatment for inhibiting established tumour growth. In contrast, 4-CPA alone was equally as effective as the combination for preventing tumour development. The potent in vivo antitumour effects of 4-CPA could not be accounted for by the known ability of PA compounds to induce expression of the RA nuclear receptor beta (RARbeta) suppressor gene. Taken together, these findings demonstrate the possibility that RAG and/or 4-CPA may serve as effective, less-toxic alternatives to 13-cis RA, which is presently being utilised for nb therapy.

  4. Lethal and sublethal endpoints observed for Artemia exposed to two reference toxicants and an ecotoxicological concern organic compound. (United States)

    Manfra, Loredana; Canepa, Sara; Piazza, Veronica; Faimali, Marco


    Swimming speed alteration and mortality assays with the marine crustacean Artemia franciscana were carried out. EC50 and LC50 values after 24-48h exposures were calculated for two reference toxicants, copper sulphate pentahydrate (CuSO4·5H2O) and Sodium Dodecyl Sulphate (SDS), and an ecotoxicological concern organic compound, Diethylene Glycol (DEG). Different end-points have been evaluated, in order to point out their sensitivity levels. The swimming speed alteration (SSA) was compared to mortality values and also to the hatching rate inhibition (literature data). SSA resulted to be more sensitive than the mortality and with a sensitivity comparable to (or even higher than) the hatching rate endpoint.

  5. LimTox: a web tool for applied text mining of adverse event and toxicity associations of compounds, drugs and genes. (United States)

    Cañada, Andres; Capella-Gutierrez, Salvador; Rabal, Obdulia; Oyarzabal, Julen; Valencia, Alfonso; Krallinger, Martin


    A considerable effort has been devoted to retrieve systematically information for genes and proteins as well as relationships between them. Despite the importance of chemical compounds and drugs as a central bio-entity in pharmacological and biological research, only a limited number of freely available chemical text-mining/search engine technologies are currently accessible. Here we present LimTox (Literature Mining for Toxicology), a web-based online biomedical search tool with special focus on adverse hepatobiliary reactions. It integrates a range of text mining, named entity recognition and information extraction components. LimTox relies on machine-learning, rule-based, pattern-based and term lookup strategies. This system processes scientific abstracts, a set of full text articles and medical agency assessment reports. Although the main focus of LimTox is on adverse liver events, it enables also basic searches for other organ level toxicity associations (nephrotoxicity, cardiotoxicity, thyrotoxicity and phospholipidosis). This tool supports specialized search queries for: chemical compounds/drugs, genes (with additional emphasis on key enzymes in drug metabolism, namely P450 cytochromes-CYPs) and biochemical liver markers. The LimTox website is free and open to all users and there is no login requirement. LimTox can be accessed at: © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Amperometric screen-printed algal biosensor with flow injection analysis system for detection of environmental toxic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Shitanda, Isao [Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 (Japan)], E-mail:; Takamatsu, Satoshi; Watanabe, Kunihiro; Itagaki, Masayuki [Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 (Japan)


    A screen-printed algal biosensor was fabricated for evaluation of toxicity of chemicals. An algal ink was prepared by mixing unicellular microalga Chlorella vulgaris cells, carbon nanotubes and sodium alginate solution. The algal ink was immobilized directly on a screen-printed carbon electrode surface using screen-printing technique. Photosynthetically generated oxygen of the immobilized algae was monitored amperometically. Responses of the algal biosensor to four toxic compounds, 6-chloro-N-ethyl-N-isopropyl-1,3,5-triazine-2,4-diamine (atrazine) and 3-(3,4-dichlorophenyl)-1,1-diethylurea (DCMU) were evaluated as inhibition ratios of the reduction current. The concentrations that gave 50% inhibition of the oxygen reduction current (IC{sup '}{sub 50}) for atrazine and DCMU were 12 and 1 {mu}mol dm{sup -3}, respectively. In comparison with the conventional algal biosensors, in which the algal cells were entrapped in an alginate gel and immobilized on the surface of a transparent indium tin oxide electrode, the present sensor is much smaller and less expensive, with the shorter assay time.

  7. A Literature Review - Problem Definition Studies on Selected Toxic Chemicals. Volume 2. Occupational Health and Safety Aspects of Phosphorus Smoke Compounds (United States)


    of pyrolysis products of SBR and pyrolysis and combustion products of Bisphenol A-epichlorohydrin epoxy resin. The toxicological studies of red and...white phosphorus, the inhalation toxicity of white phosphorus smoke and the inhalation toxicity of pyrolysis products of SBR and Bisphenol A...rats exposed to the 81 pyrolysis products of epoxy resin viii I. INTRODUCTION Phosphorus smoke compounds are used by the military to produce smoke

  8. Preliminary degradation test of toxic compounds dissolved in water using concentrated solar light. Tecnologia solar de concentracion para eliminacion mediante fotocatalisis de residuos industriales toxicos disueltos en agua

    Energy Technology Data Exchange (ETDEWEB)

    Blanco galvez, J.; Malato Rogriguez, S.


    The production and emission of hazardous chemicals wastes is a problem that is becoming more and more important in the industrialized world. Most of these wastes are toxic organic compounds appearing in low concentration in the water. solar photocatalytic water detoxification using interaction between ultraviolet light and TiO[sub 2] catalyst has therefore a strong potential in the industrial destruction of toxic organics in water. (Author)

  9. Chemical Compound, Phytochemical and Toxicity on Green Rough-backed Puffer from Cirebon District

    Directory of Open Access Journals (Sweden)

    Ginanjar Pratama


    Full Text Available This aims of study was to assess yield, nutrient content and in vitro assay of extract on green rough-backed puffer from Cirebon district. The method used in this study was the proximate analysis, phytochemicals, and BSLT test of extracts on three parts of puffer fish (meat, viscera and skin. Puffer fish used measure around 10-13 cm. The yield obtained was meat 37.80%, bone 45.71%, viscera 7.25% and skin 9.23%. Protein content showed greatest potential, protein in the fish meat was 18.54% while the skin was 25.31%. Phytochemical test showed the entire extract has a positive value for alkaloids and have a negative value on the other reagents, except meat extract on molisch test. Phytochemical test results indicated that the meat of green rough-backed puffer contain tetrodotoxin, but the amount was unknown. LC50 values in meat extract was 104.3498μg/mL, extract the viscera of 105.4564μg/mL, and the skin extract was 104.9637μg/mL. These results showed that the extract of meat, viscera and skin of the puffer fish is not toxic, although there are indications of tetrodotoxin in the flesh.Keywords: extracts, phytochemical, green rough-backed puffer, nutrient content

  10. Compound MMH01 possesses toxicity against human leukemia and pancreatic cancer cells. (United States)

    Chen, Yu-Jen; Chou, Cheng-Jen; Chang, Tun-Tschu


    MMH01 is a compound isolated from Antrodia cinnamomea. MMH01 markedly inhibited growth of human leukemia U937 and pancreatic cancer BxPC3 cells. It resulted in distinct patterns of cell cycle distribution in U937 (G2/M, sub-G1 and polyploidy) and BxPC3 cells (G0/G1 and sub-G1). The modes of cell death in U937 cells include apoptosis and mitotic catastrophe, whereas apoptosis-associated events or necrosis in BxPC3 cells. Neither mitochondrial membrane permeabilization nor caspase dependence was noted. Proteins involving mitotic catastrophe-associated cell death such as cyclin B1 and checkpoint kinase 2 were activated in U937 cells. Only slight to moderate viability inhibition was noted to human monocytes, the normal counterpart of these myeloid leukemic cells. In conclusion, MMH01 possesses cytotoxicity against human leukemia and pancreatic cancer cells.

  11. Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship (United States)

    Hui Wang; Mingyue Jiang; Shujun Li; Chung-Yun Hse; Chunde Jin; Fangli Sun; Zhuo Li


    Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and...

  12. A pharmacologically-based array to identify targets of cyclosporine A-induced toxicity in cultured renal proximal tubule cells

    Energy Technology Data Exchange (ETDEWEB)

    Sarró, Eduard, E-mail: [Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Jacobs-Cachá, Conxita, E-mail: [Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Itarte, Emilio, E-mail: [Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Meseguer, Anna, E-mail: [Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Departament de Bioquimica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain)


    Mechanisms of cyclosporine A (CsA)-induced nephrotoxicity were generally thought to be hemodynamic in origin; however, there is now accumulating evidence of a direct tubular effect. Although genomic and proteomic experiments by our group and others provided overall information on genes and proteins up- or down-regulated by CsA in proximal tubule cells (PTC), a comprehensive view of events occurring after CsA exposure remains to be described. For this purpose, we applied a pharmacologic approach based on the use of known activities of a large panel of potentially protective compounds and evaluated their efficacy in preventing CsA toxicity in cultured mouse PTC. Our results show that compounds that blocked protein synthesis and apoptosis, together with the CK2 inhibitor DMAT and the PI3K inhibitor apigenin, were the most efficient in preventing CsA toxicity. We also identified GSK3, MMPs and PKC pathways as potential targets to prevent CsA damage. Additionally, heparinase-I and MAPK inhibitors afforded partial but significant protection. Interestingly, antioxidants and calcium metabolism-related compounds were unable to ameliorate CsA-induced cytotoxicity. Subsequent experiments allowed us to clarify the hierarchical relationship of targeted pathways after CsA treatment, with ER stress identified as an early effector of CsA toxicity, which leads to ROS generation, phenotypical changes and cell death. In summary, this work presents a novel experimental approach to characterizing cellular responses to cytotoxics while pointing to new targets to prevent CsA-induced toxicity in proximal tubule cells. Highlights: ► We used a novel pharmacological approach to elucidate cyclosporine (CsA) toxicity. ► The ability of a broad range of compounds to prevent CsA toxicity was evaluated. ► CsA toxicity was monitored using LDH release assay and PARP cleavage. ► Protein synthesis, PI3K, GSK3, MMP, PKC and caspase inhibitors prevented CsA toxicity. ► We also identified ER

  13. Progress and perspectives of quantitative structure-activity relationships used for ecological risk assessment of toxic organic compounds

    Institute of Scientific and Technical Information of China (English)

    CHEN JingWen; LI XueHua; YU HaiYing; WANG YaNan; QIAO XianLiang


    Structure-activity relationship (SAR) and quantitative structure-activity relationship (QSAR), collec-tively referred to as (Q)SARs, play an important role in ecological risk assessment (ERA) of organic chemicals. (Q)SARs can fill the data gap for physical-chemical, environmental behavioral and ecotoxicological parameters of organic compounds; they can decrease experimental expenses and reduce the extent of experimental testing (especially animal testing); they can also be used to assess the uncertainty of the experimental data. With the development for several decades, (Q)SARs in envi-ronmental sciences show three features: application orientation, multidisciplinary integration, and in-telligence. Progress of (Q)SAR technology for ERA of toxic organic compounds, including endpoint selection and mathematic methods for establishing simple, transparent, easily interpretable and portable (Q)SAR models, is reviewed. The recent development on defining application domains and diagnosing outliers is summarized. Model characterization with respect to goodness-of-fit, stability and predictive power is specially presented. The purpose of the review is to promote the development of (Q)SARs orientated to ERA of organic chemicals.

  14. Progress and perspectives of quantitative structure-activity relationships used for ecological risk assessment of toxic organic compounds

    Institute of Scientific and Technical Information of China (English)


    Structure-activity relationship (SAR) and quantitative structure-activity relationship (QSAR), collec- tively referred to as (Q)SARs, play an important role in ecological risk assessment (ERA) of organic chemicals. (Q)SARs can fill the data gap for physical-chemical, environmental behavioral and ecotoxicological parameters of organic compounds; they can decrease experimental expenses and reduce the extent of experimental testing (especially animal testing); they can also be used to assess the uncertainty of the experimental data. With the development for several decades, (Q)SARs in envi- ronmental sciences show three features: application orientation, multidisciplinary integration, and in- telligence. Progress of (Q)SAR technology for ERA of toxic organic compounds, including endpoint selection and mathematic methods for establishing simple, transparent, easily interpretable and portable (Q)SAR models, is reviewed. The recent development on defining application domains and diagnosing outliers is summarized. Model characterization with respect to goodness-of-fit, stability and predictive power is specially presented. The purpose of the review is to promote the development of (Q)SARs orientated to ERA of organic chemicals.

  15. Prediction of organ toxicity endpoints by QSAR modeling based on precise chemical-histopathology annotations. (United States)

    Myshkin, Eugene; Brennan, Richard; Khasanova, Tatiana; Sitnik, Tatiana; Serebriyskaya, Tatiana; Litvinova, Elena; Guryanov, Alexey; Nikolsky, Yuri; Nikolskaya, Tatiana; Bureeva, Svetlana


    The ability to accurately predict the toxicity of drug candidates from their chemical structure is critical for guiding experimental drug discovery toward safer medicines. Under the guidance of the MetaTox consortium (Thomson Reuters, CA, USA), which comprised toxicologists from the pharmaceutical industry and government agencies, we created a comprehensive ontology of toxic pathologies for 19 organs, classifying pathology terms by pathology type and functional organ substructure. By manual annotation of full-text research articles, the ontology was populated with chemical compounds causing specific histopathologies. Annotated compound-toxicity associations defined histologically from rat and mouse experiments were used to build quantitative structure-activity relationship models predicting subcategories of liver and kidney toxicity: liver necrosis, liver relative weight gain, liver lipid accumulation, nephron injury, kidney relative weight gain, and kidney necrosis. All models were validated using two independent test sets and demonstrated overall good performance: initial validation showed 0.80-0.96 sensitivity (correctly predicted toxic compounds) and 0.85-1.00 specificity (correctly predicted non-toxic compounds). Later validation against a test set of compounds newly added to the database in the 2 years following initial model generation showed 75-87% sensitivity and 60-78% specificity. General hepatotoxicity and nephrotoxicity models were less accurate, as expected for more complex endpoints.

  16. Identification of the toxic compounds produced by Sargassum thunbergii to red tide microalgae

    Institute of Scientific and Technical Information of China (English)

    WANG Renjun; WANG You; TANG Xuexi


    The inhibitory effects of methanol extracts from the tissues of three macroalgal species on the growths of three marine red tide microalgae were assessed under laboratory conditions.Extracts of Sargassum thunbergii(Mertens ex Roth)Kuntz tissue had stronger inhibitory effects than those of either Sargassum pallidum(Turner)C.Agardh or Sargassum kjellmanianum Yendo on the growths of Heterosigrna akashiwo(Hada)Hada,Skeletonema costatum(Grey.)Grey,and Prorocentrum micans Ehrenberg.Methanol extracts of S.thunbergii were further divided into petroleum ether,ethyl acetate,butanol,and distilled water phases by liquid-liquid fractionation.The petroleum ether and ethyl acetate fractions had strong algicidal effects on the microalgae.Gas chromatography-mass spectrometry analyses of these two phases identified nine fatty acids,most of which were unsaturated fatty acids.In addition,pure compounds of four of the nine unsaturated fatty acids had effective concentrations below 5 mg/L.Therefore,unsaturated fatty acids are a component of the allelochemicals in S.thunbergii tissue.

  17. Synthesis of novel chiral compounds of purine and pyrimidine bases

    Institute of Scientific and Technical Information of China (English)

    汪毓海; 陈庆华


    The physiologically active groups such as purine and pyrimidine bases are introduced to the asymmetric ynthesis. The optically pure compounds bearing purine and pyrimidine bases (5a—5e) were prepared via the asymetric Michael addition reaction of purines and pyrimidines as Michael donators with the chiral source 5-(R)-[(1R, 2S, 5R)-menthyloxy]-2(5H)-furanone (3a), which was prepared from the natural chiral auxiliary (-)-menthol. The synthetic method was studied in detail and the new compounds were identified on the basis of their analytical data and spectroscopic data, such as [α]D20, IR, UV, 1H NMR, 13C NMR and MS. The absolute configuration of 5a was established by X-ray crystallography. The results provided an efficient synthetic route to chiral purines and pyrimidine analogues, and offered chiral sources for further research on the physiologically active compounds of chiral nucleotides.

  18. Structure-Based Virtual Screening of Commercially Available Compound Libraries. (United States)

    Kireev, Dmitri


    Virtual screening (VS) is an efficient hit-finding tool. Its distinctive strength is that it allows one to screen compound libraries that are not available in the lab. Moreover, structure-based (SB) VS also enables an understanding of how the hit compounds bind the protein target, thus laying ground work for the rational hit-to-lead progression. SBVS requires a very limited experimental effort and is particularly well suited for academic labs and small biotech companies that, unlike pharmaceutical companies, do not have physical access to quality small-molecule libraries. Here, we describe SBVS of commercial compound libraries for Mer kinase inhibitors. The screening protocol relies on the docking algorithm Glide complemented by a post-docking filter based on structural protein-ligand interaction fingerprints (SPLIF).

  19. Toxicity of Ambient Particulate Matter IV: Acute toxicity study in pulmonary hypertensive rats after exposure to model compounds for the secondary aerosol fraction of PM10 - ammonium bisulfate, ferrosulfate and nitrate

    NARCIS (Netherlands)

    Cassee FR; Boere AJF; Fokkens PHB; Dormans JAMA; Bree L van; Rombout PJA; LEO; LPI


    This (4th) report on the toxicity of ambient particulate matter (PM) presents effects of the model compounds for PM in ambient air - ammonium bisulfate, ammonium ferrosulfate and ammonium nitrate - on healthy rats and rats with monocrotaline-induced pulmonary hypertension (PH). The objective was bas

  20. Biomedical Platforms Based on Composite Nanomaterials and Cellular Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Bellucci, Stefano [INFN-Laboratori Nazionali di Frascati, Via E. Fermi 40, 00044 Frascati (Italy); Bergamaschi, A [Department of Environmental, Occupational and Social Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133 Rome (Italy); Bottini, M [INFN-Laboratori Nazionali di Frascati, Via E. Fermi 40, 00044 Frascati (Italy); Magrini, A [Department of Environmental, Occupational and Social Medicine, University of Rome Tor Vergata, Via Montpellier 1, I-00133 Rome (Italy); Mustelin, T [Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States)


    Carbon nanotubes possess unique chemical, physical, optical, and magnetic properties, which make them suitable for many uses in industrial products and in the field of nanotechnology, including nanomedicine. We describe fluorescent nanocomposites for use in biosensors or nanoelectronics. Then we describe recent results on the issue of cytotoxicity of carbon nanotubes obtained in our labs. Silica nanoparticles have been widely used for biosensing and catalytic applications due to their large surface area-to-volume ratio, straightforward manufacture, and the compatibility of silica chemistry with covalent coupling of biomolecules. Carbon nanotubes-composite materials, such as those based on Carbon nanotubes bound to nanoparticles, are suitable, in order to tailor Carbon nanotubes properties for specific applications. We present a tunable synthesis of Multi Wall Carbon nanotubes-Silica nanoparticles. The control of the nanotube morphology and the bead size, coupled with the versatility of silica chemistry, makes these structures an excellent platform for the development of biosensors (optical, magnetic and catalytic applications). We describe the construction and characterization of supramolecular nanostructures consisting of ruthenium-complex luminophores, directly grafted onto short oxidized single-walled carbon nanotubes or physically entrapped in silica nanobeads, which had been covalently linked to short oxidized single-walled carbon nanotubes or hydrophobically adsorbed onto full-length multi-walled carbon nanotubes. These structures have been evaluated as potential electron-acceptor complexes for use in the fabrication of photovoltaic devices, and for their properties as fluorescent nanocomposites for use in biosensors or nanoelectronics. Finally, we compare the toxicity of pristine and oxidized Multi Walled Carbon nanotubes on human T cells - which would be among the first exposed cell types upon intravenous administration of Carbon nanotubes in therapeutic

  1. Pyrazole-based compounds in chitosan liposomal emulsion for antimicrobial cotton fabrics. (United States)

    Nada, Ahmed; Al-Moghazy, Marwa; Soliman, Ahmed A F; Rashwan, Gehan M T; Eldawy, Taghreed Hosny Ahmed; Hassan, Ashraf Abd Elhakim; Sayed, Galal Hosni


    The chemistry of pyrazoles has gained increasing attention due to its diverse pharmacological properties such as antiviral, antagonist, antimicrobial, anticancer, anti-inflammatory, analgesic, anti-prostate cancer, herbicidal, acaricidal and insecticidal activities. 1-Phenyl pyrazole-3, 5-diamine, 4-[2-(4-methylphenyl) diazenyl] and 1H- pyrazole-3 (1), 5-diamine, 4-[2-(4-methylphenyl) diazenyl] (2) were synthesized, characterized and encapsulated into liposomal chitosan emulsions for textile finishing. The chemical modifications of cotton fabrics were demonstrated by infrared analysis. Retention of the fabric mechanical properties was investigated by reporting the tensile strength values. Synthesized pyrazole-based compounds were screened for cytotoxicity against skin fibroblast cell line and showed very limited toxicity for both compounds. Antimicrobial potentials of the treated cotton fabrics were tested against bacterial strains E. coli ATCC 8379 and Staphylococcus aureus ATCC 25923. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Phosphorus-based compounds for EUV multilayer optics materials

    NARCIS (Netherlands)

    Medvedev, V.V.; Yakshin, A.E.; Kruijs, van de R.W.E.; Bijkerk, F.


    We have evaluated the prospects of phosphorus-based compounds in extreme ultraviolet multilayer optics. Boron phosphide (BP) is suggested to be used as a spacer material in reflective multilayer optics operating just above the L-photoabsorption edge of P (λ ≈9.2 nm). Mo, Ag, Ru, Rh, and Pd were cons

  3. Bcmfs1, a novel major facilitator superfamily transporter from Botrytis cinerea, provides tolerance towards the natural toxic compounds camptothecin and cercosporin and towards fungicides

    NARCIS (Netherlands)

    Hayashi, K.; Schoonbeek, H.; Waard, De M.A.


    Bcmfs1, a novel major facilitator superfamily gene from Botrytis cinerea, was cloned, and replacement and overexpression mutants were constructed to study its function. Replacement mutants showed increased sensitivity to the natural toxic compounds camptothecin and cercosporin, produced by the plant

  4. The ABC transporter AtrB from Aspergillus nidulans is involved in resistance to all major classes of fungicides and natural toxic compounds

    NARCIS (Netherlands)

    Andrade, A.C.; Del Sorbo, G.; Nistelrooy, van J.G.M.; Waard, de M.A.


    This paper reports the functional characterization of AtrBp, an ABC transporter from Aspergillus nidulans. AtrBp is a multidrug transporter and has affinity to substrates belonging to all major classes of agricultural fungicides and some natural toxic compounds. The substrate profile of AtrBp was de

  5. Secretion of natural and synthetic toxic compounds from filamentous fungi by membrane transporters of the ATP-binding cassette and major facilitator superfamily

    NARCIS (Netherlands)

    Stergiopoulos, I.; Zwiers, L.H.; Waard, De M.A.


    This review provides an overview of members of the ATP-binding cassette (ABC) and major facilitator superfamily (MFS) of transporters identified in filamentous fungi. The most common function of these membrane proteins is to provide protection against natural toxic compounds present in the environme

  6. Soil microbial toxicity of eight polycyclic aromatic compounds: effects on nitrification, the genetic diversity of bacteria, and the total number of protozoans

    DEFF Research Database (Denmark)

    Sverdrup, Line Emilie; Ekelund, Flemming; Krogh, Paul Henning;


    Eight polycyclic aromatic compounds (PACs) were tested for their toxic effect on the soil nitrification process, bacterial genetic diversity, and the total number of protozoans (naked amoebae and heterotrophic flagellates). After four weeks of exposure in a well-characterized agricultural soil...

  7. Effectiveness of the sulfur(IV) compound, sodium bisulfite, in reducing chlorine, chlorine dioxide, and chlorite toxicity to Daphnia magna in well water and pond water. (United States)

    Yonkos, L T; Fisher, D J; Burton, D T; Whitekettle, W K; Peterille, J C


    Flow-through toxicity tests were conducted with Daphnia magna to determine the residual toxicity of chlorine, chlorine dioxide, and chlorite after treatment with the sulfur(IV) compound sodium bisulfite. Daphnids were exposed separately to 0.5-mg/L concentrations of each of the three compounds without the addition of sodium bisulfite, with a low stoichiometric dose of sodium bisulfite, and with a high stoichiometric dose of sodium bisulfite. Tests were performed in well water with a low total organic carbon (TOC) content and pond water with a high TOC content. Analysis of results indicated that sodium bisulfite did not eliminate the toxicity of chlorine dioxide or chlorite to D. magna. Total residual oxidant (TRO) concentrations were reduced and survival times were extended, but acute toxicity persisted even with a S(IV) concentration 10.0 times the stoichiometric ratio of oxidant. Mortality occurred in chlorine dioxide treatments in which no TRO was detected, indicating that standard analytical (amperometric) techniques may be inadequate to detect toxicity. Sodium bisulfite did succeed in eliminating chlorine toxicity except in pond water receiving a low (3.0x) sodium bisulfite dose. Oxidant reactions with organic substrates may have produced chlorinated residuals that were resistant to S(IV) dechlorination.

  8. Identification of compounds in heavy fuel oil that are chronically toxic to rainbow trout embryos by effects-driven chemical fractionation. (United States)

    Adams, Julie; Bornstein, Jason M; Munno, Keenan; Hollebone, Bruce; King, Thomas; Brown, R Stephen; Hodson, Peter V


    The present study isolated and identified compounds in heavy fuel oil 7102 (HFO 7102) that are bioavailable and chronically toxic to rainbow trout embryos (Oncorhynchus mykiss). An effects-driven chemical fractionation combined the chemical separation of oil with toxicity testing and chemical analyses of each fraction to identify the major classes of compounds associated with embryo toxicity. Toxicity was assessed with 2 exposure methods, a high-energy chemical dispersion of oil in water, which included oil droplets in test solutions, and water accommodated fractions which were produced by oiled gravel desorption columns, and which did not contain visible oil droplets. Fractions of HFO with high concentrations of naphthalenes, alkanes, asphaltenes, and resins were nontoxic to embryos over the range of concentrations tested. In contrast, fractions enriched with 3- to 4-ringed alkyl polycyclic aromatic hydrocarbons (PAHs) were embryotoxic, consistent with published studies of crude oils and individual alkyl PAHs. The rank order of fraction toxicity did not vary between the exposure methods and was consistent with their PAH content; fractions with higher-molecular weight alkyl PAHs were the most toxic. Exposure of juvenile trout to most fractions of HFO induced higher activities of cytochrome P450 enzymes, with a rank order of potency that varied with exposure method and differed somewhat from that of embryotoxicity. Induction reflected the bioavailability of PAHs but did not accurately predict embryotoxicity.

  9. [The mechanism of rosiglitazone compound based on network pharmacology]. (United States)

    Bai, Yu; Fan, Xue-mei; Sun, Han; Wang, Yi-ming; Liang, Qiong-lin; Luo, Guo-an


    Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.

  10. High-Tc Superconductors Based on FeAs Compounds

    CERN Document Server

    Izyumov, Yuri


    Physical properties and models of electronic structure are analyzed for a new class of high-TC superconductors which belong to iron-based layered compounds. Despite their variable chemical composition and differences in the crystal structure, these compounds possess similar physical characteristics, due to electron carriers in the FeAs layers and the interaction of these carriers with fluctuations of the magnetic order. A tremendous interest towards these materials is explained by the prospects of their practical use. In this monograph, a full picture of the formation of physical properties of these materials, in the context of existing theory models and electron structure studies, is given. The book is aimed at a broad circle of readers: physicists who study electronic properties of the FeAs compounds, chemists who synthesize them and specialists in the field of electronic structure calculations in solids. It is helpful not only to researchers active in the fields of superconductivity and magnetism, but also...

  11. Synthesis and anticonvulsant activity of certain chalcone based pyrazoline compounds

    Directory of Open Access Journals (Sweden)

    Sudhakara Rao Gerapati


    Full Text Available Convulsions are involuntary, violent, spasmodic and prolonged contractions of skeletal muscles. That means a patient may have epilepsy without convulsions and vice versa. Epilepsy is a common neurological abnormality affecting about 1% of the world population. The primary objectives of these synthesized compounds are to suppress seizures and provide neuroprotection by minimizing the effects from seizure attacks. Here some of the chalcones and chalcone based various pyrazolines were evaluated for anticonvulsant activity. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR & Mass spectroscopy. A preliminary evaluation of the prepared compounds has indicated that some of them exhibit moderate to significant anticonvulsant activity compared to a diazepam standard1-3.  All compounds were tested for their anticonvulsant activity using maximal electroshock induced convulsions (MES in mice at a dose level of 4 mg/kg.b.w. The compounds  Ph1, Ph2 , Py2 ,Py3 and Py4 have shown  to  good anticonvulsant activity when doses are administered as 25mg/ kg.b.w  , reduced the phases of seizures severity and  found to be active and also  increased survival rate. Remaining compounds are less efficacious.

  12. Chemical compound navigator: a web-based chem-BLAST, chemical taxonomy-based search engine for browsing compounds. (United States)

    Prasanna, M D; Vondrasek, Jiri; Wlodawer, Alexander; Rodriguez, H; Bhat, T N


    A novel technique to annotate, query, and analyze chemical compounds has been developed and is illustrated by using the inhibitor data on HIV protease-inhibitor complexes. In this method, all chemical compounds are annotated in terms of standard chemical structural fragments. These standard fragments are defined by using criteria, such as chemical classification; structural, chemical, or functional groups; and commercial, scientific or common names or synonyms. These fragments are then organized into a data tree based on their chemical substructures. Search engines have been developed to use this data tree to enable query on inhibitors of HIV protease ( These search engines use a new novel technique, Chemical Block Layered Alignment of Substructure Technique (Chem-BLAST) to search on the fragments of an inhibitor to look for its chemical structural neighbors. This novel technique to annotate and query compounds lays the foundation for the use of the Semantic Web concept on chemical compounds to allow end users to group, sort, and search structural neighbors accurately and efficiently. During annotation, it enables the attachment of "meaning" (i.e., semantics) to data in a manner that far exceeds the current practice of associating "metadata" with data by creating a knowledge base (or ontology) associated with compounds. Intended users of the technique are the research community and pharmaceutical industry, for which it will provide a new tool to better identify novel chemical structural neighbors to aid drug discovery.

  13. Efficient Surface Display of Diisopropylfluorophosphatase (DFPase) in E. coli for Biodegradation of Toxic Organophosphorus Compounds (DFP and Cp). (United States)

    Latifi, Ali Mohammad; Karami, Ali; Khodi, Samaneh


    Compounds including organophosphorus pesticides (OPs) and chemical nerve agents are toxic compounds synthesized recently which disrupt the mechanisms of neural transmission. Therefore, a critical requirement is the development of a bio-refining technology to facilitate the biodegradation of organophosphorus pollutants. The diisopropylfluorophosphatase (DFPase, EC from the ganglion and brain of Loligo vulgaris acts on P-F bonds present in some OPs. Intracellular production of OPs-degrading enzymes or the use of native bacteria and fungi leads to a low degradation rate of OPs due to a mass transfer issue which reduces the overall catalytic efficiency. To overcome this challenge, we expressed DFPase on the surface of E. coli for the first time by employing the N-terminal domain of the ice nucleation protein (InaV-N) as an anchoring motif. Tracking the recombinant protein confirmed that DFPase is successfully located on the outer membrane. Further studies on its activity to degrade diisopropylfluorophosphate (DFP) showed its significant ability for the biodegradation of diisopropylfluorophosphate (DFP) with a specific activity of 500 U/mg of wet cell weight. Recombinant cells could also degrade chlorpyrifos (Cp) with an activity equivalent to a maximum value of 381.44 U/ml with a specific activity of 476.75 U/mg of cell, analyzed using HPLC technique. The optimum activity of purified DFPase was found at 30 °C. A more increased activity was also obtained in the presence of glucose-mineral-salt (GMS) supplemented with tryptone and 100 mg/L Co(2+) ion. These results highlight the high potential of the InaV-N anchoring domain to produce an engineered bacterium that can be used in the bioremediation of pesticide-contaminated environments.

  14. Toxicity of eight polycyclic aromatic compounds to red clover (Trifolium pratense), ryegrass (Lolium perenne), and mustard (Sinapsis alba). (United States)

    Sverdrup, Line E; Krogh, Paul Henning; Nielsen, Torben; Kjaer, Christian; Stenersen, Jørgen


    The effect of eight polycyclic aromatic compounds (PACs) on the seed emergence and early life-stage growth of three terrestrial plants (Sinapsis alba, Trifolium pratense and Lolium perenne) were studied in a greenhouse, using a Danish agricultural soil with an organic carbon content of 1.6%. After three weeks of exposure, seed emergence and seedling weight (fresh weight and dry weight) were determined. Exposure concentrations were verified with chemical analysis. The substances tested were four polycyclic aromatic hydrocarbons (fluoranthene, pyrene, phenanthrene and fluorene), the N-, S-, and O-substituted analogues of fluorene (carbazole, dibenzothiophene and dibenzofuran, respectively), and the quinoline representative acridine. Seedling growth was a far more sensitive endpoint than seed emergence for all substances. Concentrations estimated to give a 20% reduction of seedling fresh weight (EC20-values) ranged from 36 to 290 mgkg(-1) for carbazole, 43 to 93 mgkg(-1) for dibenzofuran, 37 to 110 mgkg(-1) for dibenzothiophene, 140 to 650 mgkg(-1) for fluoranthene, 55 to 380 mgkg(-1) for fluorene, 37 to 300 mgkg(-1) for phenanthrene, and 49 to 1300 mgkg(-1) for pyrene. For acridine, no toxicity was observed within the concentration range tested (1-1000 mgkg(-1)). As illustrated by the EC20-values, there was a rather large difference in sensitivity between the species, and T. pratense was the most sensitive of the species tested.

  15. Toxic Compound, Anti-Nutritional Factors and Functional Properties of Protein Isolated from Detoxified Jatropha curcas Seed Cake

    Directory of Open Access Journals (Sweden)

    Worapot Suntornsuk


    Full Text Available Jatropha curcas is a multipurpose tree, which has potential as an alternative source for biodiesel. All of its parts can also be used for human food, animal feed, fertilizer, fuel and traditional medicine. J. curcas seed cake is a low-value by-product obtained from biodiesel production. The seed cake, however, has a high amount of protein, with the presence of a main toxic compound: phorbol esters as well as anti-nutritional factors: trypsin inhibitors, phytic acid, lectin and saponin. The objective of this work was to detoxify J. curcas seed cake and study the toxin, anti-nutritional factors and also functional properties of the protein isolated from the detoxified seed cake. The yield of protein isolate was approximately 70.9%. The protein isolate was obtained without a detectable level of phorbol esters. The solubility of the protein isolate was maximal at pH 12.0 and minimal at pH 4.0. The water and oil binding capacities of the protein isolate were 1.76 g water/g protein and 1.07 mL oil/g protein, respectively. The foam capacity and stability, including emulsion activity and stability of protein isolate, had higher values in a range of basic pHs, while foam and emulsion stabilities decreased with increasing time. The results suggest that the detoxified J. curcas seed cake has potential to be exploited as a novel source of functional protein for food applications.

  16. High-Density Real-Time PCR-Based in Vivo Toxicogenomic Screen to Predict Organ-Specific Toxicity

    Directory of Open Access Journals (Sweden)

    Laszlo G. Puskas


    Full Text Available Toxicogenomics, based on the temporal effects of drugs on gene expression, is able to predict toxic effects earlier than traditional technologies by analyzing changes in genomic biomarkers that could precede subsequent protein translation and initiation of histological organ damage. In the present study our objective was to extend in vivo toxicogenomic screening from analyzing one or a few tissues to multiple organs, including heart, kidney, brain, liver and spleen. Nanocapillary quantitative real-time PCR (QRT-PCR was used in the study, due to its higher throughput, sensitivity and reproducibility, and larger dynamic range compared to DNA microarray technologies. Based on previous data, 56 gene markers were selected coding for proteins with different functions, such as proteins for acute phase response, inflammation, oxidative stress, metabolic processes, heat-shock response, cell cycle/apoptosis regulation and enzymes which are involved in detoxification. Some of the marker genes are specific to certain organs, and some of them are general indicators of toxicity in multiple organs. Utility of the nanocapillary QRT-PCR platform was demonstrated by screening different references, as well as discovery of drug-like compounds for their gene expression profiles in different organs of treated mice in an acute experiment. For each compound, 896 QRT-PCR were done: four organs were used from each of the treated four animals to monitor the relative expression of 56 genes. Based on expression data of the discovery gene set of toxicology biomarkers the cardio- and nephrotoxicity of doxorubicin and sulfasalazin, the hepato- and nephrotoxicity of rotenone, dihydrocoumarin and aniline, and the liver toxicity of 2,4-diaminotoluene could be confirmed. The acute heart and kidney toxicity of the active metabolite SN-38 from its less toxic prodrug, irinotecan could be differentiated, and two novel gene markers for hormone replacement therapy were identified

  17. Estimation of toxicity using a Java based software tool (United States)

    A software tool has been developed that will allow a user to estimate the toxicity for a variety of endpoints (such as acute aquatic toxicity). The software tool is coded in Java and can be accessed using a web browser (or alternatively downloaded and ran as a stand alone applic...

  18. Estimation of toxicity using a Java based software tool (United States)

    A software tool has been developed that will allow a user to estimate the toxicity for a variety of endpoints (such as acute aquatic toxicity). The software tool is coded in Java and can be accessed using a web browser (or alternatively downloaded and ran as a stand alone applic...

  19. Exposure-based validation list for developmental toxicity screening assays

    NARCIS (Netherlands)

    Daston, George P.; Beyer, Bruce K.; Carney, Edward W.; Chapin, Robert E.; Friedman, Jan M.; Piersma, Aldert H.; Rogers, John M.; Scialli, Anthony R.


    Validation of alternative assays requires comparison of the responses to toxicants in the alternative assay with in vivo responses. Chemicals have been classified as "positive" or "negative" in vivo, despite the fact that developmental toxicity is conditional on magnitude of exposure. We developed a

  20. Research Progress on Ni-Based Antiperovskite Compounds

    Directory of Open Access Journals (Sweden)

    P. Tong


    Full Text Available The superconductivity in antiperovskite compound MgCNi3 was discovered in 2001 following the discovery of the superconducting MgB2. In spite of its lower superconducting transition temperature (8 K than MgB2 (39 K, MgCNi3 has attracted considerable attention due to its high content of magnetic element Ni and the cubic structure analogous to the perovskite cuprates. After years of extensive investigations both theoretically and experimentally, however, it is still not clear whether the mechanism for superconductivity is conventional or not. The central issue is if and how the ferromagnetic spin fluctuations contribute to the cooper paring. Recently, the experimental results on the single crystals firstly reported in 2007 trend to indicate a conventional s-wave mechanism. Meanwhile many compounds neighboring to MgCNi3 were synthesized and the physical properties were investigated, which enriches the physics of the Ni-based antiperovskite compounds and help understand the superconductivity in MgCNi3. In this paper, we summarize the research progress in these two aspects. Moreover, a universal phase diagram of these compounds is presented, which suggests a phonon-mediated mechanism for the superconductivity, as well as a clue for searching new superconductors with the antiperovskite structure. Finally, a few possible scopes for future research are proposed.

  1. Synthesis, structural and fungicidal studies of hydrazone based coordination compounds. (United States)

    Sharma, Amit Kumar; Chandra, Sulekh


    The coordination compounds of the Co(II), Ni(II) and Cu(II) metal ions derived from imine based ligand, benzil bis(carbohydarzone) were structurally and pharmaceutically studied. The compounds have the general stoichiometry [M(L)]X(2) and [Co(L)X(2)], where M=Ni(II) and Cu(II), and X=NO(3)(-) and Cl(-) ions. The analytical techniques like elemental analyses, molar conductance measurements, magnetic susceptibility measurements, IR, UV/Visible, NMR, ESI mass and EPR were used to study the compounds. The key IR bands, i.e., amide I, amide II and amide III stretching vibrations accounts for the tetradentate metal binding nature of the ligand. The electronic and EPR spectral results suggest the square planar Ni(II) and Cu(II) complexes (g(iso)=2.11-2.22) and tetragonal geometry Co(II) complexes (g(iso)=2.10-2.17). To explore the compounds in the biological field, they were examined against the opportunistic pathogens, i.e., Alternaria brassicae, Aspergillus niger and Fusarium oxysporum. The partial covalent character of metal-ligand bond is supported by the orbital reduction factor k (0.62-0.92) and nephalauxetic parameter β (0.55-0.57).

  2. Quadratic MOKE on Co-based Heusler compounds

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Georg; Leven, Britta; Hillebrands, Burkard [FB Physik, Landesforschungszentrum OPTIMAS, TU Kaiserslautern, 67663 Kaiserslautern (Germany); Hamrle, Jaroslav [Institute of Physics, VSB, Technical University, Ostrava (Czech Republic); Ebke, Daniel; Thomas, Andy; Reiss, Guenter [Thin Films and Physics of Nanostructures, Physics Department, Bielefeld University (Germany)


    The intensive research on Co-based Heusler compounds revealed that some of these materials show a large quadratic magneto-optical Kerr effect (QMOKE). The presence of QMOKE strongly depends on the electronic band structure. In the case of Heusler compounds the electronic bands can be modified by changing the composition or improving the crystalline structure. This work presents a systematic study on several Heusler compounds (Co{sub 2}FeSi, Co{sub 2}Fe{sub 0.5}Mn{sub 0.5}Si, Co{sub 2}MnSi and Co{sub 2}FeAl{sub 0.5}Si{sub 0.5}). The amplitude of the QMOKE is investigated as a function of the post deposition annealing temperature, which is known to improve the crystal ordering. We find that the QMOKE is increasing with the annealing temperature. From this we conclude that there is a strong correlation between the presence of QMOKE and the high crystalline ordering in Heusler compounds.

  3. Integrating the fish embryo toxicity test as triad element for sediment toxicity assessment based on the water framework directive approach

    Energy Technology Data Exchange (ETDEWEB)

    Bartzke, Mariana [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany); Gobio GmbH, Aarbergen/Kettenbach (Germany); Dept. Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research, UFZ, Leipzig (Germany); Delov, Vera [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany); Gobio GmbH, Aarbergen/Kettenbach (Germany); Ecotoxicology, Fraunhofer Inst. for Molecular Biology and Applied Ecology IME, Aachen (Germany); Stahlschmidt-Allner, Petra; Allner, Bernhard [Gobio GmbH, Aarbergen/Kettenbach (Germany); Oehlmann, Joerg [Dept. Aquatic Ecotoxicology, Goethe Univ. Frankfurt am Main (Germany)


    Purpose: The objective of this study was to complement analyses according to the European Union Water Framework Directive (WFD) with a sediment toxicity analysis as part of an integrated river assessment. To this end, Hessian water courses were analyzed using the sediment quality triad concept according to Chapman with chemical analyses, in situ effect evaluations, and ecotoxicological assessments. For the ecotoxicological assessment (fish embryo toxicity test with Danio rerio), a new evaluation scheme was developed, the fish teratogenicity index (FTI), that allows for a classification of sediments into ecological quality classes compliant to the WFD. Materials and methods sediment and macrozoobenthos samples were taken from tributaries of the rivers Fulda and Lahn. Sediments were characterized regarding particle size, carbon, heavy metals, and polyaromatic hydrocarbon content. Macroinvertebrate samples were taken via multi-habitat sampling. The fish embryo toxicity test with D. rerio was conducted as a contact assay on the basis of DIN 38415-6. Results and discussion The integrated assessment indicated a significant influence of heavy metals and carbon content on macroinvertebrate communities. The bioaccessibility of sediment pollutants were clearly demonstrated by the FTI, which showed a wide range of adverse effects. A significant linear relationship between metals and the FTI was detected. However, there was no statistically significant evidence that macroinvertebrate communities were affected by the hydromorphological quality clements at the sampling sites. Conclusions The new scheme for the assessment of fish embryo toxicity test was successfully applied. The results suggest that sediment compounds impact macroinvertebrate communities and early development of fish. It demonstrates that the quality of sediments should be evaluated on a routine basis as part of an integrated river assessment. (orig.)

  4. Semiquinone formation and DNA base damage by toxic quinones and inhibition by N-acetylcysteine (NAC)

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, D.C.; Shibamoto, T.


    Toxic, mutagenic, carcinogenic, and teratogenic effects have been reported for some quinones as well as compounds metabolized to quinones. Semiquinone radical formation, thymidine degradation, and protection by NAC were studied in a hypoxanthine/xanthine oxidase (HX/XO) system. Quinone, benzo(a)pyrene-3,6-quinone, danthron, doxorubicin, emodin, juglone, menadione, and moniliformin were tested. Diethylstilbestrolquinone, N-acetylquinoneimine, and benzoquinonediimine, hypothesized toxic metabolites of diethylstilbestrol, acetaminophen and p-phenylenediamine, respectively, were synthesized and studied. Semiquinone radical formation was assessed in a HX/XO system monitoring cytochrome C reduction. Large differences in rates of semiquinone radical formation were noted for different quinones, with V/Vo values ranging from 1.2 to 10.6. DNA base degradation, thymine or thymidine glycol formation, and thiobarbituric acid reactive substance (TBARS) production were measured in a similar system containing thymine, thymidine, calf thymus DNA, or deoxyribose. TBARS formation was observed with deoxyribose, but thymidine degradation without TBARS formation was noted with thymidine. NAC (0.5 to 10 mM) caused dose-dependent inhibition of quinone-induced cytochrome C reduction.

  5. DNA nanostructures based biosensor for the determination of aromatic compounds. (United States)

    Gayathri, S Baby; Kamaraj, P; Arthanareeswari, M; Devikala, S


    Graphite electrode was modified using multi-walled carbon nanotubes (MWCNT), chitosan (CS), glutaraldehyde (GTA) and DNA nanostructures (nsDNA). DNA nanostructures of 50 nm in size were produced from single DNA template sequence using a simple two step procedure and were confirmed using TEM and AFM analysis. The modified electrode was applied to the electrochemical detection of aromatic compounds using EIS. The modified electrode was characterized using differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). For comparison, electrochemical results derived from single stranded (50 bp length) and double stranded (50 bp length) DNA based biosensors were used. The results indicate that the modified electrode prior to nsDNA immobilization provides a viable platform that effectively promotes electron transfer between nsDNA and the electrode. The mode of binding between the nsDNA and aromatic compounds was investigated using EIS, indicating that the dominant interaction is non-covalent. nsDNA based biosensor was observed to act as an efficient biosensor in selective and sensitive identification of aromatic compounds.

  6. [Design of artificial foetor flatus based on bacterial volatile compounds]. (United States)

    Justesen, Ulrik Stenz


    Excessive flatulence can be a huge social problem. The purpose of this study was to design artificial flatus from bacterial volatile compounds to stimulate research into neutralizing measures. Anaerobic bacteria, representing a broad spectrum, from a recognized international culture collection were included. The strains were incubated in an anaerobic jar. After 24 hours the lid was removed, and the odour was evaluated by a specialist in clinical microbiology. Four different anaerobic strains were chosen for further studies based on their individual odours. In total, seven different combinations of two or three strains were tested. The combination of Bacteroides fragilis ATCC 25285, Clostridium difficile ATCC 700057 and Fusobacterium necrophorum ATCC 25286 was chosen as it had a suitably foul odour. It is possible to design artificial flatus from bacterial volatile compounds. The method is easy and inexpensive and can stimulate further research into neutralizing measures. none. none.

  7. Schiff Bases of Benzothiazol-2-ylamine and Thiazolo[5,4-b] pyridin-2-ylamine as Anticonvulsants: Synthesis, Characterization and Toxicity Profiling. (United States)

    Shukla, Rashmi; Singh, Ajeet P; Sonar, Pankaj K; Mishra, Mudita; Saraf, Shailendra K


    Schiff bases have a broad spectrum of biological activities like antiinflammatory, analgesic, antimicrobial, anticonvulsant, antitubercular, anticancer, antioxidant, anthelmintic and so forth. Thus, after a thorough perusal of literature, it was decided to conjugate benzothiazol-2-ylamine/thiazolo [5, 4-b] pyridin-2-ylamine with aromatic and heteroaromatic aldehydes to get a series of Schiff bases. Synthesis, characterization, in-silico toxicity profiling and anticonvulsant activity of the Schiff bases of Benzothiazol-2-ylamine and Thiazolo [5, 4-b] pyridin-2-ylamine. Aniline/4-aminopyridine was converted to the corresponding thiourea derivatives, which were cyclized to obtain benzothiazol-2-ylamine/thiazolo [5, 4-b] pyridin-2-ylamine. Finally, these were condensed with various aromatic and heteroaromatic aldehydes to obtain Schiff bases of benzothiazol-2-ylamine and thiazolo [5, 4-b] pyridin-2-ylamine. The synthesized compounds were characterized and screened for their anticonvulsant activity using maximal electroshock (MES) test and isoniazid (INH) induced convulsions test. In-silico toxicity profiling of all the synthesized compounds was done through "Lazar" and "Osiris" properties explorer. Majority of the compounds were more potent against MES induced convulsions than INH induced convulsions. Schiff bases of benzothiazol-2-ylamine were more effective than thiazolo [5, 4-b] pyridin-2-ylamine against MES induced convulsions. The compound benzothiazol-2-yl-(1H-indol-2-ylmethylene)-amine (VI) was the most potent member of the series against both types of convulsions. Compound VI exhibited the most significant activity profile in both the models. The compounds did not exhibit any carcinogenicity or acute toxicity in the in-silico studies. Thus, it may be concluded that the Schiff bases of benzothiazol-2-ylamine exhibit the potential to be promising and non-toxic anticonvulsant agents.

  8. A possible link between Balkan endemic nephropathy and the leaching of toxic organic compounds from Pliocene lignite by groundwater: Preliminary investigation (United States)

    Orem, W.H.; Feder, G.L.; Finkelman, R.B.


    Balkan endemic nephropathy (BEN) is a fatal kidney disease that is known to occur only in clusters of villages in alluvial valleys of tributaries of the Danube River in Bulgaria, Romania, Yugoslavia, Bosnia, and Croatia. The confinement of this disease to a specific geographic area has led to speculation that an environmental factor may be involved in the etiology of BEN. Numerous environmental factors have been suggested as causative agents for producing BEN, including toxic metals in drinking water, metal deficiency in soils of BEN areas, and environmental mycotoxins to name a few. These hypotheses have either been disproved or have failed to conclusively demonstrate a connection to the etiology of BEN, or the clustering of BEN villages. In previous work, we observed a distinct geographic relationship between the distribution of Pliocene lignites in the Balkans and BEN villages. We hypothesized that the long-term consumption of well water containing toxic organic compounds derived from the leaching of nearby Pliocene lignites by groundwater was a primary factor in the etiology of BEN. In our current work, chemical analysis using 13C nuclear magnetic resonance (13CNMR) spectroscopy indicated a high degree of organic functionality in Pliocene lignite from the Balkans, and suggested that groundwater can readily leach organic matter from these coal beds. Semi-quantitative gas chromatography/mass spectroscopy analysis of solvent extracts of groundwater from shallow wells in BEN villages indicated the presence of potentially toxic aromatic compounds, such as napthalene, fluorene, phenanthrene, and pyrene at concentrations in the ppb range. Laboratory leaching of Balkan Pliocene lignites with distilled water yielded soluble organic matter (> 500 MW) containing large amounts of aromatic structures similar to the simple/discrete aromatic compounds detected in well water from BEN villages. These preliminary results are permissive of our hypothesis and suggest that further

  9. Identification of compounds that modulate retinol signaling using a cell-based qHTS assay. (United States)

    Chen, Yanling; Sakamuru, Srilatha; Huang, Ruili; Reese, David H; Xia, Menghang


    In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-β-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling.

  10. Nanostructured Polypyrrole-Based Ammonia and Volatile Organic Compound Sensors. (United States)

    Šetka, Milena; Drbohlavová, Jana; Hubálek, Jaromír


    The aim of this review is to summarize the recent progress in the fabrication of efficient nanostructured polymer-based sensors with special focus on polypyrrole. The correlation between physico-chemical parameters, mainly morphology of various polypyrrole nanostructures, and their sensitivity towards selected gas and volatile organic compounds (VOC) is provided. The different approaches of polypyrrole modification with other functional materials are also discussed. With respect to possible sensors application in medicine, namely in the diagnosis of diseases via the detection of volatile biomarkers from human breath, the sensor interaction with humidity is described as well. The major attention is paid to analytes such as ammonia and various alcohols.

  11. Nanostructured Polypyrrole-Based Ammonia and Volatile Organic Compound Sensors

    Directory of Open Access Journals (Sweden)

    Milena Šetka


    Full Text Available The aim of this review is to summarize the recent progress in the fabrication of efficient nanostructured polymer-based sensors with special focus on polypyrrole. The correlation between physico-chemical parameters, mainly morphology of various polypyrrole nanostructures, and their sensitivity towards selected gas and volatile organic compounds (VOC is provided. The different approaches of polypyrrole modification with other functional materials are also discussed. With respect to possible sensors application in medicine, namely in the diagnosis of diseases via the detection of volatile biomarkers from human breath, the sensor interaction with humidity is described as well. The major attention is paid to analytes such as ammonia and various alcohols.

  12. Nanostructured Polypyrrole-Based Ammonia and Volatile Organic Compound Sensors (United States)

    Šetka, Milena; Drbohlavová, Jana; Hubálek, Jaromír


    The aim of this review is to summarize the recent progress in the fabrication of efficient nanostructured polymer-based sensors with special focus on polypyrrole. The correlation between physico-chemical parameters, mainly morphology of various polypyrrole nanostructures, and their sensitivity towards selected gas and volatile organic compounds (VOC) is provided. The different approaches of polypyrrole modification with other functional materials are also discussed. With respect to possible sensors application in medicine, namely in the diagnosis of diseases via the detection of volatile biomarkers from human breath, the sensor interaction with humidity is described as well. The major attention is paid to analytes such as ammonia and various alcohols. PMID:28287435

  13. Successful startup of a full-scale acrylonitrile wastewater biological treatment plant (ACN-WWTP) by eliminating the inhibitory effects of toxic compounds on nitrification. (United States)

    Han, Yuanyuan; Jin, Xibiao; Wang, Feng; Liu, Yongdi; Chen, Xiurong


    During the startup of a full-scale anoxic/aerobic (A/O) biological treatment plant for acrylonitrile wastewater, the removal efficiencies of NH(3)-N and total Kjeldahl nitrogen (TKN) were 1.29 and 0.83% on day 30, respectively. The nitrification process was almost totally inhibited, which was mainly caused by the inhibitory effects of toxic compounds. To eliminate the inhibition, cultivating the bacteria that degrade toxic compounds with patience was applied into the second startup of the biological treatment plant. After 75 days of startup, the inhibitory effects of the toxic compounds on nitrification were eliminated. The treatment plant has been operated stably for more than 3 years. During the last 100 days, the influent concentrations of chemical oxygen demand (COD), NH(3)-N, TKN and total cyanide (TCN) were 831-2,164, 188-516, 306-542 and 1.17-9.57 mg L(-1) respectively, and the effluent concentrations were 257 ± 30.9, 3.30 ± 1.10, 31.6 ± 4.49 and 0.40 ± 0.10 mg L(-1) (n = 100), respectively. Four strains of cyanide-degrading bacteria which were able to grow with cyanide as the sole carbon and nitrogen source were isolated from the full-scale biological treatment plant. They were short and rod-shaped under scanning electron microscopy (SEM) and were identified as Brevundimonas sp., Rhizobium sp., Dietzia natronolimnaea and Microbacterium sp., respectively.

  14. Synthesis, Modelling, and Anticonvulsant Studies of New Quinazolines Showing Three Highly Active Compounds with Low Toxicity and High Affinity to the GABA-A Receptor. (United States)

    Zayed, Mohamed F; Ihmaid, Saleh K; Ahmed, Hany E A; El-Adl, Khaled; Asiri, Ahmed M; Omar, Abdelsattar M


    Some novel fluorinated quinazolines (5a-j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), (13)C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.

  15. Syntheses, characterization, and anti-cancer activities of pyridine-amide based compounds containing appended phenol or catechol groups

    Indian Academy of Sciences (India)

    Afsar Ali; Deepak Bansal; Nagendra K Kaushik; Neha Kaushik; Neha Kaushik; Eun Ha Choi; Rajeev Gupta


    Several pyridine-amide compounds appended with phenol/catechol groups are synthesized. These compounds consist of protected or deprotected phenol/catechol groups and offer pyridine, amide, and phenol/catechol functional groups. All compounds have been well-characterized by various spectroscopic methods, elemental analysis, thermal studies, and crystallography. The biological activities of all compounds were investigated while a few compounds significantly decreased the metabolic viability, growth and clonogenicity of T98G cells in dose dependent manner. Accumulation of ROS was observed in T98G cells, which displayed a compromised redox status as evident from increased cellular Caspase 3/7 activity and formation of micronuclei. The in silico pharmacokinetic studies suggest that all compounds have good bioavailability, water solubility and other drug-like parameters. A few compounds were identified as the lead molecules for future investigation due to their: (a) high activity against T98G brain, H-460 lung, and SNU-80 thyroid cancer cells; (b) low cytotoxicity in non-malignant HEK and MRC-5 cells; (c) low toxic risks based on in silico evaluation; (d) good theoretical oral bioavailability according to Lipinski ‘rule of five’ pharmacokinetic parameters; and (e) better drug-likeness and drug-score values.

  16. Discovery of potent, novel, non-toxic anti-malarial compounds via quantum modelling, virtual screening and in vitro experimental validation

    Directory of Open Access Journals (Sweden)

    Kaludov Nikola


    Full Text Available Abstract Background Developing resistance towards existing anti-malarial therapies emphasize the urgent need for new therapeutic options. Additionally, many malaria drugs in use today have high toxicity and low therapeutic indices. Gradient Biomodeling, LLC has developed a quantum-model search technology that uses quantum similarity and does not depend explicitly on chemical structure, as molecules are rigorously described in fundamental quantum attributes related to individual pharmacological properties. Therapeutic activity, as well as toxicity and other essential properties can be analysed and optimized simultaneously, independently of one another. Such methodology is suitable for a search of novel, non-toxic, active anti-malarial compounds. Methods A set of innovative algorithms is used for the fast calculation and interpretation of electron-density attributes of molecular structures at the quantum level for rapid discovery of prospective pharmaceuticals. Potency and efficacy, as well as additional physicochemical, metabolic, pharmacokinetic, safety, permeability and other properties were characterized by the procedure. Once quantum models are developed and experimentally validated, the methodology provides a straightforward implementation for lead discovery, compound optimizzation and de novo molecular design. Results Starting with a diverse training set of 26 well-known anti-malarial agents combined with 1730 moderately active and inactive molecules, novel compounds that have strong anti-malarial activity, low cytotoxicity and structural dissimilarity from the training set were discovered and experimentally validated. Twelve compounds were identified in silico and tested in vitro; eight of them showed anti-malarial activity (IC50 ≤ 10 μM, with six being very effective (IC50 ≤ 1 μM, and four exhibiting low nanomolar potency. The most active compounds were also tested for mammalian cytotoxicity and found to be non-toxic, with a

  17. Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways.

    Directory of Open Access Journals (Sweden)

    Sudin Bhattacharya

    Full Text Available The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC report Toxicity Testing in the 21(st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a "toxicity pathways" (the innate cellular pathways that may be perturbed by chemicals and (b the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU. EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair.

  18. Efficacy of Topical Compound Danxiong Granules for Treatment of Dermatologic Toxicities Induced by Targeted Anticancer Therapy: A Randomized, Double-Blind, Placebo-Controlled Trial. (United States)

    Tian, Aiping; Zhou, Aiping; Bi, Xinyu; Hu, Shangying; Jiang, Zhichao; Zhang, Wen; Huang, Zhen; Shi, Hongzhe; Yang, Boyan; Chen, Wei


    Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosa Andr., Cortex Phellodendri, Geranium sibiricum L., and Flos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (P dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction.

  19. Identifying Structural Alerts Based on Zebrafish Developmental Morphological Toxicity (TDS) (United States)

    Zebrafish constitute a powerful alternative animal model for chemical hazard evaluation. To provide an in vivo complement to high-throughput screening data from the ToxCast program, zebrafish developmental toxicity screens were conducted on the ToxCast Phase I (Padilla et al., 20...


    Directory of Open Access Journals (Sweden)

    Mohanad El-Harbawi


    Full Text Available In this study, two phosphonium based ionic liquids (butyl triphenyl phosphonium chloride and hexyl triphenyl phosphonium bromide have been synthesized using quarternisation process. The toxicities of these Ionic Liquids (ILs are unknown and may be harmful to humans and the environment. Therefore, the toxicity assessment of these ILs was carried out according to the Organization for Economic Cooperation and Development (OECD 203 guideline using female guppy fish (Poecilia reticulata. The median Lethal Concentrations (LC50 have been estimated for butyl triphenyl phosphonium chloride and for hexyl triphenyl phosphonium bromide to be 73.35 and 61.36 mg L-1 respectively. Both LC50 obtained can be identified as slightly toxic ILs based on Acute Toxicity Rating Scale by Fish and Wildlife Service (FWS. The findings from this study can be used for better design of phosphonium-based ILs with consideration of their aquatic toxicities.

  1. Structure-based Drug Screening and Ligand-Based Drug Screening Toward Protein-Compound Network (United States)

    Fukunishi, Yoshifumi


    We developed two new methods to improve the accuracy of molecular interaction data using a protein-compound affinity matrix calculated by a protein-compound docking software. One method is a structure-based in silico drug screening method and another method is a ligand-based in silico drug screening method. These methods were applied to enhance the database enrichment of in silico drug screening and in silico target protein screening.

  2. Anomalies of magnetoresistance in Ce-based heavy fermion compounds (United States)

    Sluchanko, N. E.; Bogach, A. V.; Anisimov, M. A.; Glushkov, V. V.; Demishev, S. V.; Samarin, N. A.; Chistyakov, O. D.; Burkhanov, G. S.; Gabani, S.; Flachbart, K.


    Magnetoresistance Δρ(H,T) of several heavy-fermion compounds, CeAl2, CeAl3 and CeCu6, substitutional solid solutions with quantum critical behavior CeCu6-xAux (x = 0.1, 0.2) and alloys with magnetic ground state Ce(Al1-xMx)2 (M = Co, Ni, x ≤ 0.8) was studied in a wide range of temperatures (1.8-40 K) in magnetic fields up to 80 kOe. It was shown that a consistent interpretation of the field dependences of the resistance for both non-magnetic and magnetically ordered cerium-based intermetallic compounds with strong electron correlations can be achieved within the framework of an approach that accounts for scattering of charge carriers by localized magnetic moments in a metal matrix. Within this approach, three different components of the magnetoresistance of cerium intermetallic compounds were identified: the negative Brillouin contribution proportional to the local magnetization ( -Δρ/ρ˜Mloc2 ), the alternating linear contribution ( Δρ/ρ˜H ) and the magnetic component, saturating in magnetic fields below 15 kOe. In the framework of the Yosida model for the cerium alloys under study, estimates of the local magnetic susceptibility χloc(H, T0) were obtained from the magnetoresistance data. Numerical differentiation of the magnetoresistance with respect to the magnetic field and analysis of the obtained d (Δρ/ρ)/d H =f (H ,T ) dependences allowed us to reconstruct the H-T magnetic phase diagrams of the strongly correlated electron systems under study as well as to examine the effects of spin polarization and renormalization of the electronic states on charge transport both in the regime of quantum critical behavior and in the magnetically ordered state.

  3. Bilayer Effects of Antimalarial Compounds.

    Directory of Open Access Journals (Sweden)

    Nicole B Ramsey

    Full Text Available Because of the perpetual development of resistance to current therapies for malaria, the Medicines for Malaria Venture developed the Malaria Box to facilitate the drug development process. We tested the 80 most potent compounds from the box for bilayer-mediated effects on membrane protein conformational changes (a measure of likely toxicity in a gramicidin-based stopped flow fluorescence assay. Among the Malaria Box compounds tested, four compounds altered membrane properties (p< 0.05; MMV007384 stood out as a potent bilayer-perturbing compound that is toxic in many cell-based assays, suggesting that testing for membrane perturbation could help identify toxic compounds. In any case, MMV007384 should be approached with caution, if at all.

  4. Application of toxicity identification evaluation procedure to toxic industrial effluent in South Korea. (United States)

    Ra, Jin-Sung; Jeong, Tae-Yong; Lee, Sun-Hong; Kim, Sang Don


    Toxicity identification evaluation (TIE) was applied to the effluent from a pharmaceutical industrial complex, following the US EPA TIE guidelines. The whole effluent toxicity (WET) test found toxicity greater than 16toxic units (TU) in the effluent. Dissolved non-polar organic compounds were identified as the major contributor to the observed toxicity in the TIE manipulations in phases I and II. Among the 48 organic compounds identified, three compounds (i.e., acetophenone, benzoimide, and benzothiazole) were related to the pharmaceutical production procedure; however, no contribution to toxicity was predicted in the compounds. The results of the ECOSAR model, which predicts toxicity, indicated that the alkane compounds caused significant toxicity in the effluent. The toxicity test and heavy metal analysis, which used IC and ICP/MS, identified that particulate and heavy metals, such as Cu and Zn, contributed to the remaining toxicity, except dissolved organics. The results showed the applicability of the TIE method for predicting regional effluents produced by the industrial pharmaceutical complex in this study. Although the location was assumed to be affected by discharge of pharmaceutical related compounds in the river, no correlations were observed in the study. Based on the results, advanced treatment processes, such as activated carbon adsorption, are recommended for the wastewater treatment process in this location.

  5. Effects of High Toxic Boron Concentration on Protein Profiles in Roots of Two Citrus Species Differing in Boron-Tolerance Revealed by a 2-DE Based MS Approach (United States)

    Sang, Wen; Huang, Zeng-Rong; Yang, Lin-Tong; Guo, Peng; Ye, Xin; Chen, Li-Song


    Citrus are sensitive to boron (B)-toxicity. In China, B-toxicity occurs in some citrus orchards. So far, limited data are available on B-toxicity-responsive proteins in higher plants. Thirteen-week-old seedlings of “Sour pummelo” (Citrus grandis) and “Xuegan” (Citrus sinensis) was fertilized every other day until dripping with nutrient solution containing 10 μM (control) or 400 μM (B-toxicity) H3BO3 for 15 weeks. The typical B-toxic symptom only occurred in 400 μM B-treated C. grandis leaves, and that B-toxicity decreased root dry weight more in C. grandis seedlings than in C. sinensis ones, demonstrating that C. sinensis was more tolerant to B-toxicity than C. grandis. Using a 2-dimensional electrophoresis (2-DE) based MS approach, we identified 27 up- and four down-accumulated, and 28 up- and 13 down-accumulated proteins in B-toxic C. sinensis and C. grandis roots, respectively. Most of these proteins were isolated only from B-toxic C. sinensis or C. grandis roots, only nine B-toxicity-responsive proteins were shared by the two citrus species. Great differences existed in B-toxicity-induced alterations of protein profiles between C. sinensis and C. grandis roots. More proteins related to detoxification were up-accumulated in B-toxic C. grandis roots than in B-toxic C. sinensis roots to meet the increased requirement for the detoxification of the more reactive oxygen species and other toxic compounds such as aldehydes in the former. For the first time, we demonstrated that the active methyl cycle was induced and repressed in B-toxic C. sinensis and C. grandis roots, respectively, and that C. sinensis roots had a better capacity to keep cell wall and cytoskeleton integrity than C. grandis roots in response to B-toxicity, which might be responsible for the higher B-tolerance of C. sinensis. In addition, proteins involved in nucleic acid metabolism, biological regulation and signal transduction might play a role in the higher B-tolerance of C. sinensis.

  6. Materials Chemistry and Performance of Silicone-Based Replicating Compounds.

    Energy Technology Data Exchange (ETDEWEB)

    Brumbach, Michael T.; Mirabal, Alex James; Kalan, Michael; Trujillo, Ana B; Hale, Kevin


    Replicating compounds are used to cast reproductions of surface features on a variety of materials. Replicas allow for quantitative measurements and recordkeeping on parts that may otherwise be difficult to measure or maintain. In this study, the chemistry and replicating capability of several replicating compounds was investigated. Additionally, the residue remaining on material surfaces upon removal of replicas was quantified. Cleaning practices were tested for several different replicating compounds. For all replicating compounds investigated, a thin silicone residue was left by the replica. For some compounds, additional inorganic species could be identified in the residue. Simple solvent cleaning could remove some residue.

  7. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila. (United States)

    Shieh, Shin-Yi; Bonini, Nancy M


    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insights into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG-repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified 160 genes that are differentially expressed specifically in CAG100 flies. Functional annotation clustering analysis revealed several broad ontologies enriched in the CAG100 gene list, including iron ion binding and nucleotide binding. Intriguingly, transcripts for the Hsp70 genes, a powerful suppressor of polyQ and other human neurodegenerative diseases, were also upregulated. We therefore tested and showed that upregulation of heat shock protein 70 mitigates CAG-repeat RNA toxicity. We then assessed whether other modifiers of the pathogenic, expanded Ataxin-3 polyQ protein could also modify the CAG-repeat RNA toxicity. This approach identified the co-chaperone Tpr2, the transcriptional regulator Dpld, and the RNA-binding protein Orb2 as modifiers of both polyQ protein toxicity and CAG-repeat RNA-based toxicity. These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease.

  8. Cholinesterases as scavengers for organophosphorus compounds: Protection of primate performance against soman toxicity. (Reannouncement with new availability information)

    Energy Technology Data Exchange (ETDEWEB)

    Doctor, B.P.; Blick, D.W.; Caranto, G.; Castro, C.A.; Gentry, M.K.


    The present treatment for poisoning by organophosphates consists of multiple drugs such as carbamates, antimuscarinics, and reactivators in pre- and post-exposure modalities. Recently an anticonvulsant, diazapam, has been included as a post-exposure drug to reduce convulsions and increase survival. Most regimens are effective in preventing lethality from organophosphate exposure but do not prevent toxic effects and incapacitation observed in animals and likely to occur in humans. Use of enzymes such as cholinesterases as pretreatment drugs for sequestration of highly toxic organophosphate anticholinesterases and alleviation of side effects and performance decrements was successful in animals, including non-human primates. Pretreatment of rhesus monkeys with fetal bovine serum acetyleholinesterase protected them against lethal effects of soman (up to 5 LD50) and prevented signs of OP toxicity. Monkeys pretreated with fetal bovine serum acetylcholinesterase were devoid of behavioral incapacitation after soman exposure, as measured by serial probe recognition or primate equilibrium platform performance tasks. Use of acetylcholinesterase as a single pretreatment drug provided greater protection against both lethal and behavioral effects of potent organophosphates than current multicomponent drug treatments that prevent neither signs of toxicity nor behavioral deficits. Cholinesterases, Pretreatment, Toxicity, Organophosphates, Soman, Scavengers.

  9. A quantitative structure-activity relationship for the acute toxicity of some epoxy compounds to the guppy

    NARCIS (Netherlands)

    Deneer, J.W.; Sinnige, T.L.; Seinen, W.; Hermens, J.L.M.


    The 14 day LC50 values of various epoxy compounds to the guppy (Poecilia reticulata) were determined, and investigated through the construction of a quantitative structure-activity relationship (QSAR). Both hydrophobicity and alkylating potency of the compounds are found to be necessary parameters f

  10. Spontaneous and Dosing Route-related Lung Lesions in Beagle Dogs from Oral Gavage and Inhalation Toxicity Studies: Differentiation from Compound-induced Lesions. (United States)

    Mukaratirwa, Sydney; Garcia, Begonya; Isobe, Kaori; Petterino, Claudio; Bradley, Alys


    This study was conducted to characterize lung microscopic lesions in control beagle dogs from inhalation and oral gavage toxicity studies, to determine differences associated with the route of administration, and to discuss distinguishing features from compound-induced lung lesions. Samples from 138 control dogs from oral gavage studies and 124 control dogs from inhalation (vehicle control) studies were evaluated microscopically. There was no significant sex-related difference in the incidence of all lesions. Perivascular mononuclear cell infiltration, centriacinar mixed cell infiltration, bronchopneumonia, subpleural septal fibrosis, and alveolar macrophage accumulation were the most common lesions. Aspiration pneumonia was more common in dogs from gavage studies, suggesting reflux after gavage dosing or accidental administration of test formulation as possible causes. Centriacinar mixed cell infiltration was more common in dogs from inhalation studies, suggesting mild irritation by the vehicles used. Vascular lesions, which included pulmonary arteriopathy and smooth muscle mineralization, were observed in a few animals. Some of the spontaneous lesions are similar to lesions induced by test compounds. Compared to spontaneous lesions, compound-induced lesions tend to be multifocal or diffuse, follow a pattern of distribution (e.g., centriacinar, perivascular, and interstitial), show a dose response in the incidence and severity, and may show cell-specific toxicity.

  11. Mg-based compounds for hydrogen and energy storage (United States)

    Crivello, J.-C.; Denys, R. V.; Dornheim, M.; Felderhoff, M.; Grant, D. M.; Huot, J.; Jensen, T. R.; de Jongh, P.; Latroche, M.; Walker, G. S.; Webb, C. J.; Yartys, V. A.


    Magnesium-based alloys attract significant interest as cost-efficient hydrogen storage materials allowing the combination of high gravimetric storage capacity of hydrogen with fast rates of hydrogen uptake and release and pronounced destabilization of the metal-hydrogen bonding in comparison with binary Mg-H systems. In this review, various groups of magnesium compounds are considered, including (1) RE-Mg-Ni hydrides (RE = La, Pr, Nd); (2) Mg alloys with p-elements (X = Si, Ge, Sn, and Al); and (3) magnesium alloys with d-elements (Ti, Fe, Co, Ni, Cu, Zn, Pd). The hydrogenation-disproportionation-desorption-recombination process in the Mg-based alloys (LaMg12, LaMg11Ni) and unusually high-pressure hydrides synthesized at pressures exceeding 100 MPa (MgNi2H3) and stabilized by Ni-H bonding are also discussed. The paper reviews interrelations between the properties of the Mg-based hydrides and p- T conditions of the metal-hydrogen interactions, chemical composition of the initial alloys, their crystal structures, and microstructural state.

  12. Structure-activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating Mycobacterium tuberculosis. (United States)

    Lilienkampf, Annamaria; Mao, Jialin; Wan, Baojie; Wang, Yuehong; Franzblau, Scott G; Kozikowski, Alan P


    Tuberculosis (TB) remains as a global pandemic that is aggravated by a lack of health care, the spread of HIV, and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains. New anti-TB drugs are urgently required to shorten the long 6-12 month treatment regimen and to battle drug-resistant Mtb strains. We have identified several potent quinoline-based anti-TB compounds, bearing an isoxazole containing side-chain. The most potent compounds, 7g and 13, exhibited submicromolar activity against the replicating bacteria (R-TB), with minimum inhibitory concentrations (MICs) of 0.77 and 0.95 microM, respectively. In general, these compounds also had micromolar activity against the nonreplicating persistent bacteria (NRP-TB) and did not show toxicity on Vero cells up to 128 microM concentration. Compounds 7g and 13 were shown to retain their anti-TB activity against rifampin, isoniazid, and streptomycin resistant Mtb strains. The results suggest that quinoline-isoxazole-based anti-TB compounds are promising leads for new TB drug development.

  13. Removal of antibiotics in wastewater by enzymatic treatment with fungal laccase - Degradation of compounds does not always eliminate toxicity. (United States)

    Becker, Dennis; Varela Della Giustina, Saulo; Rodriguez-Mozaz, Sara; Schoevaart, Rob; Barceló, Damià; de Cazes, Matthias; Belleville, Marie-Pierre; Sanchez-Marcano, José; de Gunzburg, Jean; Couillerot, Olivier; Völker, Johannes; Oehlmann, Jörg; Wagner, Martin


    In this study, the performance of immobilised laccase (Trametes versicolor) was investigated in combination with the mediator syringaldehyde (SYR) in removing a mixture of 38 antibiotics in an enzymatic membrane reactor (EMR). Antibiotics were spiked in osmosed water at concentrations of 10μg·L(-1) each. Laccase without mediator did not reduce the load of antibiotics significantly. The addition of SYR enhanced the removal: out of the 38 antibiotics, 32 were degraded by >50% after 24h. In addition to chemical analysis, the samples' toxicity was evaluated in two bioassays (a growth inhibition assay and the Microtox assay). Here, the addition of SYR resulted in a time-dependent increase of toxicity in both bioassays. In cooperation with SYR, laccase effectively removes a broad range of antibiotics. However, this enhanced degradation induces unspecific toxicity. If this issue is resolved, enzymatic treatment may be a valuable addition to existing water treatment technologies.

  14. Toxicity and bioaccumulation of xenobiotic organic compounds in the presence of aqueous suspensions of aggregates of nano-C60

    DEFF Research Database (Denmark)

    Baun, Anders; Sørensen, Sara Nørgaard; Rasmussen, R.F.


    The potential of C60-nanoparticles (Buckminster fullerenes) as contaminant carriers in aqueous systems was studied in a series of toxicity tests with algae (Pseudokirchneriella subcapitata) and crustaceans (Daphnia magna). Four common environmental contaminants (atrazine, methyl parathion...... in 4-days-old D. magna was studied with and without addition of C60 in aqueous suspensions. It was found that 85% of the added phenanthrene sorbed to C60-aggregates >200nm whereas about 10% sorption was found for atrazine, methyl parathion, and pentachlorophenol. In algal tests, the presence of C60...... as water phase concentrations. Thus, results from both toxicity tests show that phenanthrene sorbed to C60-aggregates is available for the organisms. For atrazine and methyl parathion no statistically significant differences in toxicities could be observed in algal and daphnid tests as a result...

  15. Evaluation of Cellular Toxicity of Three Denture Base Acrylic Resins


    Ebrahimi Saravi, M.; M. Vojdani; Bahrani, F


    Objective This study aimed to evaluate the cellular toxicity of two newly-released acrylic resins (Futura Gen and GC Reline Hard) in comparison with the conventional heat-cure resin (Meliodent). Materials and Methods: Sample discs from each acrylic resin were placed in 24-well culture plates along with L929 mouse fibroblast cell line. A mixture of the RPMI 1640 medium, antibiotics and 10% FBS was added to the plates and the specimens were incubated in a CO2 incubator. The amount of light abso...

  16. Epigallocatechin-3-gallate and related phenol compounds redirect the amyloidogenic aggregation pathway of ataxin-3 towards non-toxic aggregates and prevent toxicity in neural cells and Caenorhabditis elegans animal model. (United States)

    Visentin, Cristina; Pellistri, Francesca; Natalello, Antonino; Vertemara, Jacopo; Bonanomi, Marcella; Gatta, Elena; Penco, Amanda; Relini, Annalisa; De Gioia, Luca; Airoldi, Cristina; Regonesi, Maria E; Tortora, Paolo


    The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards non-toxic, soluble, SDS-resistant aggregates. Here, we have characterized other related phenol compounds, although smaller in size, i.e. (-)-epigallocatechin gallate (EGC), and gallic acid (GA). We analysed the aggregation pattern of ATX3-Q55 and of the N-terminal globular Josephin domain (JD) by assessing the time course of the soluble protein, as well its structural features by FTIR and AFM, in the presence and the absence of the mentioned compounds. All of them redirected the aggregation pattern towards soluble, SDS-resistant aggregates. They also prevented the appearance of ordered side-chain hydrogen bonding in ATX3-Q55, which is the hallmark of polyQ-related amyloids. Molecular docking analyses on the JD highlighted three interacting regions, including the central, aggregation-prone one. All three compounds bound to each of them, although with different patterns. This might account for their capability to prevent amyloidogenesis. Saturation transfer difference NMR experiments also confirmed EGCG and EGC binding to monomeric JD. ATX3-Q55 pre-incubation with any of the three compounds prevented its calcium-influx-mediated cytotoxicity towards neural cells. Finally, all the phenols significantly reduced toxicity in a transgenic Caenorhabditis elegans strain expressing an expanded ATX3. Overall, our results show that the three polyphenols act in a substantially similar manner. GA, however, might be more suitable for antiamyloid treatments due to its simpler structure and higher chemical stability. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email:


    Directory of Open Access Journals (Sweden)

    Frog Boris Nikolaevich


    Full Text Available Whenever environmental pollution by sulphur compounds is under discussion, the latter contemplate those compounds that may be subjected to consideration through the employment of methods of analytical control. First of all, sulphates and volatile compounds of partially or completely restored sulphur, such as SO2, H2S, methyl sulphur compounds (merkaptans, dimethyl sulphide, dimethyl disulphide and others may be subjected to control. Elementary sulphur that is contained in the water is difficult to analyze. At the same time, an extensive group of water-soluble compounds of restored sulphur is not considered by numerous nature protection organizations. As a rule, they do not possess distinct analytical properties. The latter include any organic and inorganic thio-acids and their combinations with ions of transitive metals, in particular, with ions of monovalent copper. Microcolloidal (nano- particles of FeS may also be included into this group of compounds. The objective of the article is to generate the awareness of those compounds of reduced sulphur that are out of control. By virtue of this article, the authors apply to specialists in water treatment, water conditioning and water quality regulation.

  18. New aqueous rechargeable power sources based on intercalation compounds

    Energy Technology Data Exchange (ETDEWEB)

    Tian, S.; Liu, L.L.; Qu, Q.T.; Wu, Y.P. [Fudan Univ., New Energy and Materials Laboratory, Shanghai (China). Dept. of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials


    Lithium ion batteries have gained global attention because of their intercalation mechanism. However, when the capacity is very large for large-scale energy storage of electricity, the safety of lithium ion batteries is a challenge. The safest energy storage for large-scale energy storage is based on aqueous solutions. This paper reported on the latest developments related to the results of aqueous rechargeable power sources based on intercalation compounds, notably aqueous rechargeable lithium batteries (ARLBs) and hybrid supercapacitors. The paper provided background information on ARLBs and discussed the use of polypyrrole as anode materials. It was found that this polymer could be doped and un-doped during cycling, which demonstrated excellent cycling behaviour. The paper also discussed the enhancement of the reversible capacity of lithium manganese oxide (LiMn{sub 2}O{sub 4}) and lithium cobalt dioxide (LiCoO{sub 2}) in ARLBs by adopting novel preparation technologies. It was concluded that ARLBs and the new hybrid supercapacitors show significant potential for practical applications in large-scale energy storage that are needed to make advances in sustainable development. 7 refs.

  19. Granular activated carbon for simultaneous adsorption and biodegradation of toxic oil sands process-affected water organic compounds. (United States)

    Islam, Md Shahinoor; Zhang, Yanyan; McPhedran, Kerry N; Liu, Yang; Gamal El-Din, Mohamed


    Naphthenic acids (NAs) released into oil sands process-affected water (OSPW) during bitumen processing in Northern Alberta are problematic for oil sands industries due to their toxicity in the environment and resistance to degradation during conventional wastewater treatment processes. Granular activated carbon (GAC) has shown to be an effective media in removing biopersistent organics from wastewater using a combination of adsorption and biodegradation removal mechanisms. A simultaneous GAC (0.4 g GAC/L) adsorption and biodegradation (combined treatment) study was used for the treatment of raw and ozonated OSPW. After 28 days of batch treatment, classical and oxidized NAs removals for raw OSPW were 93.3% and 73.7%, and for ozonated OSPW were 96.2% and 77.1%, respectively. Synergetic effects of the combined treatment process were observed in removals of COD, the acid extractable fraction, and oxidized NAs, which indicated enhanced biodegradation and bioregeneration in GAC biofilms. A bacteria copy number >10(8) copies/g GAC on GAC surfaces was found using quantitative real time polymerase chain reaction after treatment for both raw and ozonated OSPW. A Microtox(®) acute toxicity test (Vibrio fischeri) showed effective toxicity removal (>95.3%) for the combined treatments. Therefore, the simultaneous GAC adsorption and biodegradation treatment process is a promising technology for the elimination of toxic OSPW NAs.

  20. Fluorescence-based assay as a new screening tool for toxic chemicals (United States)

    Moczko, Ewa; Mirkes, Evgeny M.; Cáceres, César; Gorban, Alexander N.; Piletsky, Sergey


    Our study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.

  1. Documents for Recommended Toxicity Equivalency Factors for Human Health Risk Assessments of Dioxin and Dioxin-Like Compounds (United States)

    This document describes the U.S. Environmental Protection Agency’s (U.S. EPA’s) updated approach for evaluating the human health risks from exposures to environmental media containing dioxin-like compounds (DLCs).

  2. Estimation of the critical effect level for pollution prevention based on oyster embryonic development toxicity test: the search for reliability. (United States)

    da Cruz, A C S; Couto, B C; Nascimento, I A; Pereira, S A; Leite, M B N L; Bertoletti, E; Zagatto, P


    In spite of the consideration that toxicity testing is a reduced approach to measure the effects of pollutants on ecosystems, the early-life-stage (ELS) tests have evident ecological relevance because they reflect the possible reproductive impairment of the natural populations. The procedure and validation of Crassostrea rhizophorae embryonic development test have shown that it meets the same precision as other U.S. EPA tests, where EC(50) is generally used as a toxicological endpoint. However, the recognition that EC(50) is not the best endpoint to assess contaminant effects led U.S. EPA to recently suggest EC(25) as an alternative to estimate xenobiotic effects for pollution prevention. To provide reliability to the toxicological test results on C. rhizophorae embryos, the present work aimed to establish the critical effect level for this test organism, based on its reaction to reference toxicants, by using the statistical method proposed by Norberg-King (Inhibition Concentration, version 2.0). Oyster embryos were exposed to graded series of reference toxicants (ZnSO(4) x 7H(2)O; AgNO(3); KCl; CdCl(2)H(2)O; phenol, 4-chlorophenol and dodecyl sodium sulphate). Based on the obtained results, the critical value for C. rhizophorae embryonic development test was estimated as EC(15). The present research enhances the emerging consensus that ELS tests data would be adequate for estimating the chronic safe concentrations of pollutants in the receiving waters. Based on recommended criteria and on the results of the present research, zinc sulphate and 4-chlorophenol have been pointed out, among the inorganic and organic compounds tested, as the best reference toxicants for C. rhizophorae ELS-test.

  3. Toxicology of organochlorine compounds. The influence of chlorine substitutes on the toxicity of organic molecules. Toxikologie chlororganischer Verbindungen. Der Einfluss von Chlorsubstituenten auf die Toxizitaet organischer Molekuele

    Energy Technology Data Exchange (ETDEWEB)

    Henschler, D. (Wuerzburg Univ. (Germany). Inst. fuer Pharmakologie und Toxikologie)


    Industrial production cannot be imagined without organochlorine compounds. Most of them, however have a toxic, or even carcinogenic or genetically damaging influence on the human organism. In this book, D. Henschler introduces the reader to the state of the art in research. Tables indicate the toxicological effects of the most important organochlorine compound classes used in the industry. Anyone interested in more detail finds comprehensive reference to literature on this subject. The clear and scientifically sound evaluation of data show potential dangers of organochlorines and provides a basis for the development of safer and better alternative substances. This is a very topical reference book not only for toxicologists, chemists and environmental scientists but for anyone who is interested in one of the most important problems of industrial societies. (orig.)

  4. Cell death effects of resin-based dental material compounds and mercurials in human gingival fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Reichl, Franz-Xaver [Walther-Straub-Institute of Pharmacology and Toxicology, Munich (Germany); Ludwig-Maximilians-University, Department of Operative Dentistry and Periodontology, Munich (Germany); Esters, Magali; Simon, Sabine; Seiss, Mario [Walther-Straub-Institute of Pharmacology and Toxicology, Munich (Germany); Kehe, Kai [Bundeswehr Institute of Pharmacology and Toxicology, Munich (Germany); Kleinsasser, Norbert [University of Regensburg, Head and Neck Surgery, Department of Otolaryngology, Regensburg (Germany); Folwaczny, Matthias; Glas, Juergen; Hickel, Reinhard [Ludwig-Maximilians-University, Department of Operative Dentistry and Periodontology, Munich (Germany)


    In order to test the hypothesis that released dental restorative materials can reach toxic levels in human oral tissues, the cytotoxicities of the resin-based dental (co)monomers hydroxyethylmethacrylate (HEMA), triethyleneglycoldimethacrylate (TEGDMA), urethanedimethacrylate (UDMA), and bisglycidylmethacrylate (BisGMA) compared with methyl mercury chloride (MeHgCl) and the amalgam component mercuric chloride (HgCl{sub 2}) were investigated on human gingival fibroblasts (HGF) using two different test systems: (1) the modified XTT-test and (2) the modified H 33342 staining assay. The HGF were exposed to various concentrations of the test-substances in all test systems for 24 h. All tested (co)monomers and mercury compounds significantly (P<0.05) decreased the formazan formation in the XTT-test. EC{sub 50} values in the XTT assay were obtained as half-maximum-effect concentrations from fitted curves. Following EC{sub 50} values were found (mean [mmol/l]; s.e.m. in parentheses; n=12; * significantly different to HEMA): HEMA 11.530 (0.600); TEGDMA* 3.460 (0.200); UDMA* 0.106 (0.005); BisGMA* 0.087 (0.001); HgCl{sub 2}* 0.013 (0.001); MeHgCl* 0.005 (0.001). Following relative toxicities were found: HEMA 1; TEGDMA 3; UDMA 109; BisGMA 133; HgCl{sub 2} 887; MeHgCl 2306. A significant (P<0.05) increase of the toxicity of (co)monomers and mercurials was found in the XTT-test in the following order: HEMA < TEGDMA < UDMA < BisGMA < HgCl{sub 2} < MeHgCl. TEGDMA and MeHgCl induced mainly apoptotic cell death. HEMA, UDMA, BisGMA, and HgCl{sub 2} induced mainly necrotic cell death. The results of this study indicate that resin composite components have a lower toxicity than mercury from amalgam in HGF. HEMA, BisGMA, UDMA, and HgCl{sub 2} induced mainly necrosis, but it is rather unlikely that eluted substances (solely) can reach concentrations, which might induce necrotic cell death in the human physiological situation, indicating that other (additional) factors may be involved in

  5. Enhancing biodegradation of C16-alkyl quaternary ammonium compounds using an oxygen-based membrane biofilm reactor. (United States)

    Lai, YenJung Sean; Ontiveros-Valencia, Aura; Ilhan, Zehra Esra; Zhou, Yun; Miranda, Evelyn; Maldonado, Juan; Krajmalnik-Brown, Rosa; Rittmann, Bruce E


    Quaternary ammonium compounds (QACs) (e.g., hexadecyltrimethyl-ammonium bromide, CTAB) are emerging contaminants with widespread use as surfactants and disinfectants. Because the initial step of QAC biodegradation is mono-oxygenation, QAC degraders require O2, but normal aeration leads to serious foaming. Here, we developed and tested an oxygen-based membrane biofilm reactor (O2-MBfR) that delivers O2 by diffusion through the walls of hollow-membranes to a biofilm accumulating on the outer surface of membranes. The O2-MBfR sustained QAC biodegradation even with high and toxic QAC input concentrations, up to 400 mg/L CTAB. Bubbleless O2 transfer completely eliminated foaming, and biofilm accumulation helped the QAC biodegraders resist toxicity. Pseudomonas, Achromobacter, Stenotrophomonas, and members of the Xanthomonadaceae family were dominant in the biofilm communities degrading CTAB, and their proportions depended on the O2-delivery capacity of the membranes. Bacteria capable of biodegrading QACs often harbor antibiotic resistance genes (ARGs) that help them avoid QAC toxicity. Gene copies of ARGs were detected in biofilms and liquid, but the levels of ARGs were 5- to 35-fold lower in the liquid than in the biofilm. In summary, the O2-MBfR achieved aerobic biodegradation of CTAB with neither foaming nor toxicity, and it also minimized the spread of ARGs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. [A system for predicting the toxicity and hazard of chemical substances, based on the joint use of logistic and numerical methods]. (United States)

    Kharchevnikova, N V


    A version of a logical combinatorial intellectual system (DMS system) has been developed to predict the toxicity and hazards of chemical substances. The system is based on the combined description of the substances, which includes both structural and numerical descriptors, particularly those characterizing the reactivity of compounds or their metabolites. The selection of numerical descriptors is based on the classification of processes of the interaction of the substance with the body in accordance with the key stage of the mechanism responsible for its toxic action. The new version of the DSM system takes into account the fact that the toxicity and hazard of chemicals are frequently determined by their bioactivation. Examples of how to apply the system to the prediction of carcinogenicity are given.

  7. Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels. (United States)

    Defarge, Nicolas; Takács, Eszter; Lozano, Verónica Laura; Mesnage, Robin; Spiroux de Vendômois, Joël; Séralini, Gilles-Eric; Székács, András


    Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH), the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18-2000 times for co-formulants, 8-141 times for formulations), and not the declared active ingredient glyphosate (G) alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine-POEA and alkyl polyglucoside-APG) and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI) value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

  8. Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

    Directory of Open Access Journals (Sweden)

    Nicolas Defarge


    Full Text Available Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH, the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations, and not the declared active ingredient glyphosate (G alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

  9. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation. (United States)

    Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios


    Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically.

  10. Quantitative structure activity relationships (QSAR) for binary mixtures at non-equitoxic ratios based on toxic ratios-effects curves. (United States)

    Tian, Dayong; Lin, Zhifen; Yin, Daqiang


    The present study proposed a QSAR model to predict joint effects at non-equitoxic ratios for binary mixtures containing reactive toxicants, cyanogenic compounds and aldehydes. Toxicity of single and binary mixtures was measured by quantifying the decrease in light emission from the Photobacterium phosphoreum for 15 min. The joint effects of binary mixtures (TU sum) can thus be obtained. The results showed that the relationships between toxic ratios of the individual chemicals and their joint effects can be described by normal distribution function. Based on normal distribution equations, the joint effects of binary mixtures at non-equitoxic ratios ( [Formula: see text]) can be predicted quantitatively using the joint effects at equitoxic ratios ( [Formula: see text]). Combined with a QSAR model of [Formula: see text]in our previous work, a novel QSAR model can be proposed to predict the joint effects of mixtures at non-equitoxic ratios ( [Formula: see text]). The proposed model has been validated using additional mixtures other than the one used for the development of the model. Predicted and observed results were similar (p>0.05). This study provides an approach to the prediction of joint effects for binary mixtures at non-equitoxic ratios.

  11. Antioxidant compounds in the seaweed Gelidiella acerosa protects human Peripheral Blood Mononuclear Cells against TCDD induced toxicity. (United States)

    Ilavarasi, K; Chermakani, P; Arif Nisha, S; Sheeja Malar, D; Pandima Devi, K


    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental toxin formed as an unintentional by-product of incomplete combustion. Several therapeutic approaches have evolved to combat its toxicity since it elicits immunotoxicity, neurotoxicity, hepatotoxicity, carcinogenicity and lethality. Search for drugs from natural resources especially from seaweeds has become intense due to their enormous pharmacological potential. Hence, the present study aims at revealing the protective effect of methanolic extract of G. acerosa (MEGA) in Peripheral Blood Mononuclear Cells (PBMC) against TCDD induced toxicity, by assessing the antioxidant, anti-apoptotic and cytoprotective activities. The results of antioxidant assays suggests that MEGA reverted TCDD induced toxicity by causing an alteration in the levels of antioxidant enzymes (Catalase [CAT], Superoxide dismutase [SOD], Glutathione peroxidase [GPx], Glutathione-S-transferase [GST]) and Glutathione [GSH]. The results of lipid peroxidation assay and protein carbonyl content reveal that MEGA protects PBMC from TCDD induced macromolecular damage. MEGA was found to exhibit significant (p TCDD induced oxidative DNA damage. Levels of phase-I detoxification enzymes determined by EROD assay and semi-quantitative RT-PCR showed that TCDD up-regulates the expression of CYP1A1 and upon co-treatment with MEGA, the expression got slightly decreased suggesting its protective role. Preliminary phytochemical analysis demonstrates that the extract is rich in cardiac glycosides and terpenoids. LC-MS analysis revealed the presence of antioxidants including caffeic acid, phytol and mannoheptulose in MEGA, which could be attributed for the observed protective effect against TCDD induced toxicity.

  12. Stimulation of Ideas through Compound-Based Bibliometrics: Counting and Mapping Chemical Compounds for Analyzing Research Topics in Chemistry, Physics, and Materials Science. (United States)

    Barth, Andreas; Marx, Werner


    Counting compounds (rather than papers or citations) offers a new perspective for quantitative analyses of research activities. First of all, we can precisely define (compound-related) research topics and access the corresponding publications (scientific papers as well as patents) as a measure of research activity. We can also establish the time evolution of the publications dealing with specific compounds or compound classes. Moreover, the mapping of compounds by establishing compound-based landscapes has some potential to visualize the compound basis of research topics for further research activities. We have analyzed the rare earth compounds to give an example of a broad compound class. We present the number of the currently existing compounds and of the corresponding publications as well as the time evolution of the papers and patents. Furthermore, we have analyzed the rare earth cuprates (copper oxides) as an example of a narrower compound class to demonstrate the potential of mapping compounds by compound-based landscapes. We have quantified the various element combinations of the existing compounds and revealed all element combinations not yet realized in the synthesis within this compound class. Finally, we have analyzed the quasicrystal compound category as an example of a compound class that is not defined by a specific element combination or a molecular structure.

  13. Crystal growth iron based pnictide compounds; Kristallzuechtung eisenbasierter Pniktidverbindungen

    Energy Technology Data Exchange (ETDEWEB)

    Nacke, Claudia


    The present work is concerned with selected crystal growth method for producing iron-based superconductors. The first part of this work introduces significant results of the crystal growth of BaFe{sub 2}As{sub 2} and the cobalt-substituted compound Ba(Fe{sub 1-x}Co{sub x}){sub 2}As{sub 2} with x{sub Nom} = 0.025, 0.05, 0.07, 0.10 and 0.20. For this purpose a test procedure for the vertical Bridgman method was developed. The second part of this work contains substantial results for growing a crystal of LiFeAs and the nickel-substituted compound Li{sub 1-δ}Fe{sub 1-x}Ni{sub x}As with x{sub Nom} = 0.015, 0.025, 0.05, 0.06, 0.075 and 0.10. For this purpose a test procedure for the melt flow process has been developed successfully. [German] Die vorliegende Arbeit befasst sich mit ausgewaehlten Kristallzuechtungsverfahren zur Herstellung eisenbasierter Supraleiter. Der erste Teil dieser Arbeit fuehrt wesentliche Ergebnisse der Kristallzuechtung von BaFe{sub 2}As{sub 2} sowie der Cobalt-substituierten Verbindung Ba(Fe{sub 1-x}Co{sub x}){sub 2}As{sub 2} mit x{sub Nom} =0.025, 0.05, 0.07, 0.10 und 0.20 auf. Hierzu wurde eine Versuchsdurchfuehrung fuer das vertikale Bridgman-Verfahren konzipiert, mit welcher erfolgreich Kristalle dieser Zusammensetzungen gezuechtet wurden. Der zweite Teil dieser Arbeit enthaelt wesentliche Ergebnisse zur Kristallzuechtung von LiFeAs sowie der Nickel-substituierten Verbindung Li{sub 1-δ}Fe{sub 1-x}Ni{sub x}As mit x{sub Nom} = 0.015, 0.025, 0.05, 0.06, 0.075 und 0.10. Hierfuer wurde erfolgreich eine Versuchsdurchfuehrung fuer das Schmelzfluss-Verfahren entwickelt.

  14. Superconductivity in BiS2-based compounds (United States)

    Yazici, Duygu


    Polycrystalline samples of Ln O0.5F0.5BiS2 (Ln = La, Ce, Pr, Nd, Yb) were synthesized by solid-state reaction. These compounds form in a tetragonal structure with space group P 4 / nmm conforming to the CeOBiS2 crystal structure. Electrical resistivity, magnetic susceptibility and specific heat measurements were performed on all of the samples. All of the compounds exhibit superconductivity in the range 1.9 K - 5.4 K, and the YbO0.5F0.5BiS2 sample was also found to exhibit magnetic order (probably antiferromagnetic order) at ~2.7 K that appears to coexist with superconductivity below 5.4 K. Electron-doping appears to induce superconductivity in the BiS2-based superconductors as partial substitution of F for O is necessary to observe superconductivity. This was further demonstrated in a study where trivalent La+3 was partially substituted with tetravalent Th+4, Hf+4, Zr+4, and Ti+4, all of which induced superconductivity. We also observed that substitution of divalent Sr+2 for La+3 (hole doping) does not induce superconductivity. Electrical resistivity measurements were also performed under applied pressure on Ln O0.5F0.5BiS2 (Ln = La, Ce, Pr, Nd) up to ~3 GPa and down to 1 K. These studies revealed a universal behavior where the systems are tuned away from semi-conducting behavior towards metallic behavior. The superconducting states were stabilized by applied pressure, so that Tc increased in all of the rare earth members listed. At a critical pressure Pc, Tc increases rapidly from a low Tc phase to a distinct high Tc phase, after which additional pressure no longer suppressed the semiconducting behavior in the normal state [3,4]. In addition, the metallization of NdO0.5F0.5BiS2 also occurs at Pc. Research was supported by the US AFOSR MURI FA9550-09-1-0603, US DOE DE-FG02-04-ER46105 and NNSA DE-NA0001841.

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

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


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

  16. Security evaluation of compounded microbial flocculant

    Institute of Scientific and Technical Information of China (English)

    马放; 王博; 范春; 杨基先; 李百祥; 刘艳滨


    A new kind of compounded microbial flocculant (CMBF) for water and wastewater treatment has been developed through biological technology. In order to discuss its biological security, four groups of experiments, rat acute toxicity test via mouth, salmonella assay in vitro, mouse micronucleus in vivo test and teratogenesis test were conducted to evaluate its general toxicity, genotoxicity and generative toxicity. The experimental results showed that this type of compounded microbial fiocculant was a substantial non-toxic substance based on the fact that LD50 value was over 10 mg/kg. The results from salmonella in vivo test and mouse micronucleus in vivo test revealed that the compounded microbial flocculant is a genetically non-toxic substance. Furthermore, compounded microbial flocculant has little effect on the growth of all the rats, and any morphologic abnormal phenomenon hasnt appeared.

  17. A review of toxicity studies on graphene-based nanomaterials in laboratory animals. (United States)

    Ema, Makoto; Gamo, Masashi; Honda, Kazumasa


    We summarized the findings of toxicity studies on graphene-based nanomaterials (GNMs) in laboratory mammals. The inhalation of graphene (GP) and graphene oxide (GO) induced only minimal pulmonary toxicity. Bolus airway exposure to GP and GO caused acute and subacute pulmonary inflammation. Large-sized GO (L-GO) was more toxic than small-sized GO (S-GO). Intratracheally administered GP passed through the air-blood barrier into the blood and intravenous GO distributed mainly in the lungs, liver, and spleen. S-GO and L-GO mainly accumulated in the liver and lungs, respectively. Limited information showed the potential behavioral, reproductive, and developmental toxicity and genotoxicity of GNMs. There are indications that oxidative stress and inflammation may be involved in the toxicity of GNMs. The surface reactivity, size, and dispersion status of GNMs play an important role in the induction of toxicity and biodistribution of GNMs. Although this review paper provides initial information on the potential toxicity of GNMs, data are still very limited, especially when taking into account the many different types of GNMs and their potential modifications. To fill the data gap, further studies should be performed using laboratory mammals exposed using the route and dose anticipated for human exposure scenarios.

  18. Toxicity of eight polycyclic aromatic compounds to the red clover (Trifolium pratense), ryegrass (Lolium perenne), and mustard (Sinapsis alba)

    DEFF Research Database (Denmark)

    Sverdrup, L. E.; Krogh, P. H.; Nielsen, T.


    The effect of eight polycyclic aromatic compounds (PACs) on the seed emergence and early life-stage growth of three terrestrial plants (Sinapsis alba, Trifolium pratense and Lolium perenne) were studied in a greenhouse, using a Danish agricultural soil with an organic carbon content of 1.6%. After...

  19. Toxicity of eight polycyclic aromatic compounds to red clover (Trifolium pratense), ryegrass (Lolium perenne), and mustard (Sinapsis alba)

    DEFF Research Database (Denmark)

    Sverdrup, L.E.; Krogh, P.H.; Nielsen, T.


    The effect of eight polycyclic aromatic compounds (PACs) on the seed emergence and early life-stage growth of three terrestrial plants (Sinapsis alba, Trifolium pratense and Lolium perenne) were studied in a greenhouse, using a Danish agricultural soil with an organic carbon content of 1.6%. After...

  20. Mammalian Toxicity of Munition Compounds. Phase II. Effects of Multiple Doses. Part III. 2,6-Dinitrotoluene (United States)


    calcium concentration can produce tetany ,./ which resembles the neuromuscular signs seen. However, this requires hypocalcemia of 3.5 meq/liter or less...treated with 2,4-DNT was not sufficient to induce tetany . Similar neuro- muscular effects were observed in dogs given either compounds, but the

  1. Variation in the toxicity of arsenic compounds to microorganisms and the suppression of the inhibitory effects by phosphate. (United States)

    Da Costa, E W


    The toxicity of potassium arsenate, as measured by retardation or inhibition of growth on solid nutrient media, showed wide variation among different fungi but was consistently reduced by the addition of large amounts of potassium phosphate, with both arsenic-sensitive and arsenic-tolerant fungi. Poria monticola was completely inhibited by 0.0025 M arsenate but was progressively less inhibited as the phosphate content of the medium increased and grew slowly at 0.04 M arsenate when 0.16 M KH(2)PO(4) was added. Cladosporium herbarum showed 36% reduction in growth at 0.08 M arsenate in a low-phosphate medium, but when 0.01 M KH(2)PO(4) was added, arsenate concentrations up to 0.64 M (at which the medium contains 4.8% As) caused no reduction in growth rate. Addition of phosphate also reduced the toxicity of potassium arsenite but not that of dimethyl sodium arsonate (sodium cacodylate). The counteracting effect of phosphate on arsenate toxicity was found to occur with every one of a wide variety of microorganisms tested. The author interprets the results as supporting the thesis that the fungitoxicity of arsenate is due to its competitive interference with phosphorus in oxidative phosphorylation and not to a reaction with the -SH groups of essential proteins. The latter mechanism is, however, probably operative with dimethyl sodium arsonate. The practical implications of the counter-inhibition phenomenon in laboratory investigations and standard tests of arsenical fungicides, in biochemical research, and in the commercial use of arsenical biocides are set out.

  2. A nationwide register-based survey of baclofen toxicity. (United States)

    Kiel, Louise Bendix; Hoegberg, Lotte Christine Groth; Jansen, Tejs; Petersen, John Asger; Dalhoff, Kim Peder


    To study the use and misuse (poisonings) of baclofen in the time period of 2007-2012 and to evaluate the severity and clinical symptoms of poisonings including ingested baclofen. The National Patient Register (NPR) was searched for admissions due to baclofen poisonings from 2007 to 2012. The search was conducted with ICD-10 codes for poisoning, self-harm and suicide, and coupled with the baclofen ATC code. All enquiries about baclofen to the Danish Poison Information Centre (DPIC) in the same period were evaluated. Demographic and clinical data were extracted, and the poisonings were classified according to the Poison Severity Score. The number of baclofen poisonings did not increase from 2007 to 2012. Thirty-eight admissions with baclofen poisoning were registered at the NPR; however, only one-third of the reviewed DPIC cases were registered at the NPR with the correct coding. In the group of severely poisoned patients (PSS 3), three patients had only ingested baclofen (mean 2000 mg; SD 500 mg) and eight patients had ingested baclofen together with alcohol or psychotropic drugs (mean 900 mg; SD 641 mg). All patients presented with deep coma and respiratory depression. Additionally, seizures and cardiovascular events (mild hypo- or hypertension and bradycardia) occurred. There is a substantial degree of underreporting of baclofen poisonings in Denmark. Symptoms of baclofen poisoning progress very fast, and toxicity was observed even with doses as low as 150 mg. We therefore recommend that observation and treatment of these patients should be carried out in an intermediate- or intensive care unit. The most important treatment is the maintenance of a protected airway and respiration.

  3. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels, supplement to: Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W; Riebesell, Ulf; Gao, Kunshan (2015): Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels. Nature Communications, 6, 8714

    KAUST Repository

    Jin, Peng


    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  4. Application of Thermal Desorption Unit (TDU) to treat low-toxicity mineral oil base cuttings in Barinas District, Venezuela

    Energy Technology Data Exchange (ETDEWEB)

    Rendon, Ruben [Petroleos de Venezuela, Caracas (Venezuela); Luzardo, Janeth; Alcoba, Alcides [M-I SWACO, Houston, TX (United States)


    The potential environmental impact of oil-based drill cuttings is generating increased scrutiny in the oil and gas industry. If left untreated, oil-based cuttings not only increase the risk of environmental liabilities, but also affect revenue, as drilling generates wastes that in most cases require special treatment before disposal. Consequently, the oil industry is looking for technologies to help minimize environmental liabilities. Accordingly, the Barinas District of PDVSA has started a pilot trial to treat oil-based drilling cuttings by applying thermal desorption technology. The main objective of this technology is recovering trapped hydrocarbons, while minimizing wastes and preparing solids to be disposed of through a mobile treatment plant. This novel technology has been used worldwide to treat organic pollutants in soil. Thermal desorption is a technology based on the application of heat in soils polluted with organic compounds. With this technology, target temperatures vary according to the type and concentration of detected pollutants along with its characterization, in such a way that compounds are disposed of by volatilization. As part of the integral waste management development along with the pilot trial for hydrocarbon-contaminated solid waste treatment, trials on soils were undertaken by applying process-generated ashes in equally-sized bins, with different mixtures (ashes, ashes organic material, ashes-organic material-sand, ashes-land). The resulting process offers an immediate soil remediation and final disposal solution for toxic and dangerous waste. (author)

  5. Bcmfs1, a novel major facilitator superfamily transporter from Botrytis cinerea, provides tolerance towards the natural toxic compounds camptothecin and cercosporin and towards fungicides. (United States)

    Hayashi, Keisuke; Schoonbeek, Henk-Jan; De Waard, Maarten A


    Bcmfs1, a novel major facilitator superfamily gene from Botrytis cinerea, was cloned, and replacement and overexpression mutants were constructed to study its function. Replacement mutants showed increased sensitivity to the natural toxic compounds camptothecin and cercosporin, produced by the plant Camptotheca acuminata and the plant pathogenic fungus Cercospora kikuchii, respectively. Overexpression mutants displayed decreased sensitivity to these compounds and to structurally unrelated fungicides, such as sterol demethylation inhibitors (DMIs). A double-replacement mutant of Bcmfs1 and the ATP-binding cassette (ABC) transporter gene BcatrD was more sensitive to DMI fungicides than a single-replacement mutant of BcatrD, known to encode an important ABC transporter of DMIs. The sensitivity of the wild-type strain and mutants to DMI fungicides correlated with Bcmfs1 expression levels and with the initial accumulation of oxpoconazole by germlings of these isolates. The results indicate that Bcmfs1 is a major facilitator superfamily multidrug transporter involved in protection against natural toxins and fungicides and has a substrate specificity that overlaps with the ABC transporter BcatrD. Bcmfs1 may be involved in protection of B. cinerea against plant defense compounds during the pathogenic phase of growth on host plants and against fungitoxic antimicrobial metabolites during its saprophytic phase of growth.

  6. Stevia-derived compounds attenuate the toxic effects of ectopic lipid accumulation in the liver of obese mice: a transcriptomic and metabolomic study. (United States)

    Holvoet, Paul; Rull, Anna; García-Heredia, Anabel; López-Sanromà, Sílvia; Geeraert, Benjamine; Joven, Jorge; Camps, Jordi


    There is a close interaction between Type 2 Diabetes, obesity and liver disease. We have studied the effects of the two most abundant Stevia-derived steviol glycosides, stevioside and rebaudioside A, and their aglycol derivative steviol on liver steatosis and the hepatic effects of lipotoxicity using a mouse model of obesity and insulin resistance. We treated ob/ob and LDLR-double deficient mice with stevioside (10 mg⋅kg(-1)⋅day-1 p.o., n = 8), rebaudioside A (12 mg⋅kg(-1)⋅day-1 p.o., n = 8), or steviol (5 mg⋅kg(-1)⋅day(-1) p.o., n = 8). We determined their effects on liver steatosis and on the metabolic effects of lipotoxicity by histological analysis, and by combined gene-expression and metabolomic analyses. All compounds attenuated hepatic steatosis. This could be explained by improved glucose metabolism, fat catabolism, bile acid metabolism, and lipid storage and transport. We identified PPARs as important regulators and observed differences in effects on insulin resistance, inflammation and oxidative stress between Stevia-derived compounds. We conclude that Stevia-derived compounds reduce hepatic steatosis to a similar extent, despite differences in effects on glucose and lipid metabolism, and inflammation and oxidative stress. Thus our data show that liver toxicity can be reduced through several pathophysiological changes. Further identification of active metabolites and underlying mechanisms are warranted.

  7. Ternary alloys based on II-VI semiconductor compounds

    CERN Document Server

    Tomashyk, Vasyl; Shcherbak, Larysa


    Phase Equilibria in the Systems Based on ZnSSystems Based on ZnSeSystems Based on ZnTeSystems Based on CdSSystem Based on CdSeSystem Based on CdTeSystems Based on HgSSystems Based on HgSeSystems Based on HgTeIndexReferences appear at the end of each chapter.

  8. Toxic effects of chlorinated organic compounds and potassium dichromate on growth rate and photosynthesis of marine phytoplankton

    DEFF Research Database (Denmark)

    Kusk, Kresten Ole; Nyholm, Niels


    The toxic effects of potassium dichromate (K2Cr2O7), 3,4-dichloroaniline (DCA) and 2,4-dichlorophenol (DCP) on the photosynthesis of natural marine phytoplankton and five species of marine microalgae were investigated. Effect concentrations corresponding to a 50 % depression of photosynthesis (6h...... EC50) were found within relatively narrow ranges of 3.3–7.2 mg/l and 1.5–12 mg/l for DCA and DCP respectively, whereas the sensitivities towards K2Cr2O7 varied much more. The effects of DCA and DCP on the growth rate of some species were also investigated. EC50 values for DCP and DCA were found...

  9. Selection of cryoprotectants based on their toxic effects on oyster gametes and embryos. (United States)

    Nascimento, Iracema A; Leite, Maria Bernadete N L; Sampaio de Araújo, Milena Maria; Sansone, Giovanni; Pereira, Solange A; do Espírito Santo, E Maristela


    Cryopreservation is a valuable tool for aquaculture by providing continuous seed production, regardless of the spawning seasons. This study aimed to select the least toxic among the cryoprotectants dimethyl sulfoxide (Me2SO), propylene glycol (PG), and methanol (MET) based on their toxicological effects on Crassostrea rhizophorae gametes and trochophores. They were exposed for 10, 20, and 30 min to a range of concentrations of those cryoprotectants. The endpoint was EC15-24 h (effective concentration which causes abnormalities in 15% of the population exposed to the cryoprotectants for 24 h), recently determined as the chronic value (the concentration at which chronic effects are first observed) for C. rhizophorae embryonic phases. There were no significant differences (p>0.05) among the exposure times in Me2SO toxic effects to either gametes or trochophores. For MET, the increase in exposure time resulted in higher toxicity for gametes, but not for trochophores, while for PG there was a significant (p>0.05) increase in toxicity with the increase of exposure for trochophores and spermatozoa, but not for oocytes. For gametes, MET was the most toxic among the cryoprotectants, while PG was the most toxic for trochophores.

  10. Solvent-based dissolution method to sample gas-phase volatile organic compounds for compound-specific isotope analysis. (United States)

    Bouchard, Daniel; Hunkeler, Daniel


    An investigation was carried out to develop a simple and efficient method to collect vapour samples for compound specific isotope analysis (CSIA) by bubbling vapours through an organic solvent (methanol or ethanol). The compounds tested were benzene and trichloroethylene (TCE). The dissolution efficiency was tested for different air volume injections, using flow rates ranging from 25ml/min to 150ml/min and injection periods varying between 10 and 40min. Based on the results, complete mass recovery for benzene and TCE in both solvents was observed for the flow rates of 25 and 50ml/min. However, small mass loss was observed at increased flow rate. At 150ml/min, recovery was on average 80±17% for benzene and 84±10% for TCE, respectively in methanol and ethanol. The δ(13)C data measured for benzene and TCE dissolved in both solvents were reproducible and were stable independently of the volume of air injected (up to 6L) or the flow rate used. The stability of δ(13)C values hence underlines no isotopic fractionation due to compound-solvent interaction or mass loss. The development of a novel and simple field sampling technique undertaken in this study will facilitate the application of CSIA to diverse gas-phase volatile organic compound studies, such as atmospheric emissions, soil gas or vapour intrusion.

  11. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologically based kinetic modeling. (United States)

    Louisse, Jochem; Bosgra, Sieto; Blaauboer, Bas J; Rietjens, Ivonne M C M; Verwei, Miriam


    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity data obtained from in vitro assays for risk assessment, in vitro concentration-response data need to be translated into in vivo dose-response data that are needed to obtain points of departure for risk assessment, like a benchmark dose (BMD). In the present study, we translated in vitro concentration-response data of the retinoid all-trans-retinoic acid (ATRA), obtained in the differentiation assay of the embryonic stem cell test, into in vivo dose-response data using a physiologically based kinetic model for rat and human that is mainly based on kinetic model parameter values derived using in vitro techniques. The predicted in vivo dose-response data were used for BMD modeling, and the obtained BMDL10 values [lower limit of the 95 % confidence interval on the BMD at which a benchmark response equivalent to a 10 % effect size (BMR10) is reached (BMD10)] for rat were compared with BMDL10 values derived from in vivo developmental toxicity data in rats reported in the literature. The results show that the BMDL10 values from predicted dose-response data differ about sixfold from the BMDL10 values obtained from in vivo data, pointing at the feasibility of using a combined in vitro-in silico approach for defining a point of departure for toxicological risk assessment.

  12. Evaluation of the Toxicity of Virola sebifera Crude Extracts, Fractions and Isolated Compounds on the Nest of Leaf-Cutting Ants

    Directory of Open Access Journals (Sweden)

    Keylla Utherdyany Bicalho


    Full Text Available The phytochemical study of Virola sebifera leaves led to the isolation of three lignans: (+-sesamin, (−-hinokinin, and (−-kusunokinin and three flavonoids: quercetin-3-O-α-L-rhamnoside, quercetin-3-O-β-D-glucoside, and quercetin-3-methoxy-7-O-β-D-glucoside by using techniques as high-speed counter-current chromatography and high-performance liquid chromatography. The crude extracts, fractions, and isolated compounds were evaluated for their insecticidal and fungicidal potential against Atta sexdens rubropilosa and its symbiotic fungus Leucoagaricus gongylophorus. The bioassay results showed a high insecticidal activity for the methanol crude extract of the leaves of V. sebifera and its n-hexane, dichloromethane and ethyl acetate fractions. The fungicidal bioassay revealed high toxicity of the lignans against L. gongylophorus.

  13. Microbial toxicity of the insensitive munitions compound, 2,4-dinitroanisole (DNAN), and its aromatic amine metabolites. (United States)

    Liang, Jidong; Olivares, Christopher; Field, Jim A; Sierra-Alvarez, Reyes


    2,4-Dinitroanisole (DNAN) is an insensitive munitions compound considered to replace conventional explosives such as 2,4,6-trinitrotoluene (TNT). DNAN undergoes facile microbial reduction to 2-methoxy-5-nitroaniline (MENA) and 2,4-diaminoanisole (DAAN). This study investigated the inhibitory effect of DNAN, MENA, and DAAN toward various microbial targets in anaerobic (acetoclastic methanogens) and aerobic (heterotrophs and nitrifiers) sludge, and the bioluminescent bacterium, Aliivibrio fischeri, used in the Microtox assay. Aerobic heterotrophic and nitrifying batch experiments with DAAN could not be performed because the compound underwent extensive autooxidation in these assays. DNAN severely inhibited methanogens, nitrifying bacteria, and A. fischeri (50% inhibitory concentrations (IC50) ranging 41-57μM), but was notably less inhibitory to aerobic heterotrophs (IC50>390 μM). Reduction of DNAN to MENA and DAAN lead to a marked decrease in methanogenic inhibition (i.e., DNAN>MENA≈DAAN). Reduction of all nitro groups in DNAN also resulted in partial detoxification in assays with A. fischeri. In contrast, reduction of a single nitro group did not alter the inhibitory impact of DNAN toward A. fischeri and nitrifying bacteria given the similar IC50 values determined for MENA and DNAN in these assays. These results indicate that reductive biotransformation could reduce the inhibitory potential of DNAN.

  14. Toxicity testing of heavy metals with the Rhizobium-legume symbiosis: High sensitivity to cadmium and arsenic compounds. (United States)

    Neumann, H; Bode-Kirchhoff, A; Madeheim, A; Wetzel, A


    Legume root nodules are the site of biological nitrogen fixation in the Rhizobium-legume symbiosis. Nodules are structures unique to this symbiosis and they are morphologically as well as physiologically distinct from other plant organs. Organic substances affecting the macro- or microsymbionts vitality, such as PAHs (WETZEL: et al., 1991), reduce nodulation even before visible damage to the plant can be detected. We present data that the formation of nodules (nodulation) may also serve for ecotoxicological evaluation of heavy metals in different binding states. Tests were performed in petri dishes with alfalfa (lucerne) seedlings inoculated with Rhizobium meliloti. Cultivation took place in growth cabinets with carefully standardized and documented growth conditions. Data from stressed plants was recorded after 14 days of cultivation on contaminated substrate. A dose responsive decrease in nodulation was found after application of cadmium acetate, cadmium iodide, cadmium chloride, sodium salts of arsenate and arsenite, arsenic pentoxide, and lead nitrate, whereas lead acetate showed no effect up to a concentration of 3 microM. The dose response curves were used to calculate EC10, EC50 and EC90 values. EC50 values for cadmium compounds range from 1.5 to 9.5 pM. Testing different arsenic compounds results in EC50 from 2.6 to 20.1 microM. EC50 of lead nitrate is 2.2 microM. The sensitivity, reproducibility and reliability of this test system is discussed compared to established biotests.

  15. Contact and fumigant toxicity of hexane flower bud extract of Syzygium aromaticum and its compounds against Pediculus humanus capitis (Phthiraptera: Pediculidae). (United States)

    Bagavan, Asokan; Rahuman, Abdul Abdul; Kamaraj, Chinnaperumal; Elango, Gandhi; Zahir, Abdul Abduz; Jayaseelan, Chidambaram; Santhoshkumar, Thirunavukkarasu; Marimuthu, Sampath


    The head lice, Pediculus humanus capitis De Geer is an obligate ectoparasite of humans that causes pediculosis capitis, a nuisance for millions of people worldwide, with high prevalence in children. P. humanus capitis has been treated by methods that include the physical remotion of lice, various domestic treatments, and conventional insecticides. None of these methods render complete protection, and there is clear evidence for the evolution of resistance and cross-resistance to conventional insecticides. Non-toxic alternative options are hence needed for head lice treatment and/or prevention, and natural products from plants are good candidates for safer control agents that may provide good anti-lice activity. The plant extracts are good and safe alternatives due to their low toxicity to mammals and easy biodegradability. The present study carried out the pediculocidal activity using the hexane flower bud extract of Syzygium aromaticum (Myrtaceae) against P. humanus capitis examined by direct contact and fumigant toxicity (closed- and open-container methods) bioassay. The chemical composition of S. aromaticum flower bud hexane extract was analyzed by gas chromatography-mass spectrometry. The major chemical constituent (58.79%) of flower bud hexane extract S. aromaticum was identified as chavibetol (5-allyl-2-methoxyphenol) by comparison of mass spectral data and retention times. The hexane extract of S. aromaticum was subjected to gas chromatography analysis, and totally 47 compounds were detected, of which chavibetol was predominantly present. The other major constituents present in the hexane extract were eugenol acetate (phenol,2-methoxy-4-(2-propenyl)-,acetate (15.09%), caryophyllene-(I1) (2,6,10,10-tetramethyl bicyclo [7.2.0] undeca-1,6-diene (13.75%), caryophyllene oxide (3.04%), 2,6,6,9-tetramethyl-1,4,8-cycloundecatriene (1.67%), and copaene (1.33%). The filter paper contact bioassay study showed pronounced pediculicidal activity in the flower bud hexane

  16. Low-temperature synthesis and investigations on photocatalytic activity of nanoparticles BiFeO3 for methylene blue and methylene orange degradation and some toxic organic compounds (United States)

    Nhiem Dao, Ngoc; Luu, Minh Dai; Chuc Pham, Ngoc; Dung Doan, Trung; Nguyen, Thi Ha Chi; Bac Nguyen, Quang; Lim Duong, Thi


    The photocatalytic BiFeO3 perovskite nanoparticles were fabricated by gel combustion method using polyvinyl alcohol and corresponding metal nitrate precursors under the optimum mild conditions such as pH 2, gel formation temperature of 80 °C, metal/polyvinyl alcohol molar ratio of 1/3, metal molar ratio Bi/Fe of 1/1 and calcination temperature at 500 °C for 2 h. The prepared sample was characterized by x-ray diffraction, field scanning electron microscopy, transmission electron microscopy, Brunauer-Emmetl-Teller nitrogen adsorption method at 77 K, energy dispersive x-ray spectroscopy, ultraviolet-visible light spectrophotometry, and thermal analysis. The effects of molar ratios of starting material and calcination temperature on phase formation and morphology were investigated. The degradation of methylene blue, methylene orange and some toxic organic compounds such as phenol and diazinon under visible light irradiation by photocatalytic BiFeO3 nanoparticles were evaluated at different parameters and conditions such as the light intensity determined from the light source to the measured sample, the addition H2O2, reaction time and the regeneration performance. Obtained results showed that the synthesized perovskite BiFeO3 nanoparticles for the optimized sample have a size smaller than 50 nm and the high mean surface area of 50 m2 g-1. Degradation efficiency was almost 90.0% for methylene blue and 80.0% for methylene orange with added H2O2 after 30 min of reaction. After the 3rd time of regeneration, the BiFeO3 nanoparticles still have 92.8% of the degradation performance for removing methylene blue. Phenol and diazinon toxic compound were degraded with the performance of 92.42% and 85.7%, respectively, for 150 min

  17. Protective activity of medicinal plants and their isolated compounds against the toxic effects from the venom of Naja (cobra) species. (United States)

    Shabbir, Arham; Shahzad, Muhammad; Masci, Paul; Gobe, Glenda C


    Various medicinal plants have protective properties against the toxicities of the venom of cobra snake (Naja species). They may be used as local first aid for the treatment of snakebite victims, and can significantly inhibit lethality, cardio-, neuro-, nephro- and myotoxicity, hemorrhage, and respiratory paralysis induced by the cobra snake venom. The plants or their extracts may also complement the benefits of conventional anti-serum treatment. This review provides information on the protective, anti-venom, properties of medicinal plants against snakebites from cobras. In addition, it identifies knowledge gaps and suggests further research opportunities. The literature was searched using databases including Google Scholar, PubMed, ScienceDirect, Scopus and Web of Science. The searches were limited to peer-reviewed journals written in English with the exception of some books and a few articles in foreign languages. The plants possess neutralization properties against different cobra venom enzymes, such as hyaluronidase, acetylcholinesterase, phospholipase A2 and plasma proteases. Different active constituents that show promising activity against the effects of cobra venom include lupeol acetate, β-sitosterol, stigmasterol, rediocides A and G, quercertin, aristolochic acid, and curcumin, as well as the broad chemical groups of tannins, glycoproteins, and flavones. The medicinal plants can increase snakebite victim survival time, decrease the severity of toxic signs, enhance diaphragm muscle contraction, block antibody attachment to venom, and inhibit protein destruction. In particular, the cardiovascular system is protected, with inhibition of blood pressure decline and depressed atrial contractility and rate, and prevention of damage to heart and vessels. The designs of experimental studies that show benefits, or otherwise, of use of medicinal plants have some limitations: deficiency in identification and isolation of active constituents responsible for

  18. Geochemical investigations into the retention of reactive carbon compounds for toxic heavy metals. Final report; Geochemische Untersuchungen zur Retention von reaktiven Kohlenstoffverbindungen fuer toxische Schwermetalle. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Kupsch, H.; Mansel, A.; Crustewitz, C.


    The composition, reactivity and stability of reactive organic carbon compounds adsorbed on geogenic matrices was investigated. The surface deposits of NOM and its dependence on geochemical parameters was investigated in selected geomatrices. The retention of toxic heavy metals on these surface deposits of NOM was investigated in consideration of the presence of hydroxy species and inorganic ligands. The investigations of the reactivity of the NOM species requires analyses of these compounds and of the heavy metals in the ultratracer region. This was possible by means of radiochemical methods that were further developed in the context of this project. Radioactive labeling of identified reactive carbon compounds, e.g. with radioactive iodine, on the one hand, and the use of radioactive Cu, Pb, Hg isotopes on the other hand enabled speciation analyses in the binary systems (heavy metal + geomatrix, heavy metal + reactive carbon compounds, reactive carbon compounds + geomatrix) and especially in the ternary system (heavy metal + geomatrix + reactive carbon compounds) in defined conditions. The special labelling techniques were a precondition for distribution measurements in the near-natural, low concentration range. (orig.) [German] Ziel des Projektes war es, mit der vorhandenen Analytik und Expertise die Zusammensetzung, die Reaktivitaet und die Stabilitaet der auf den geogenen Matrizes sorbierten reaktiven organischen Kohlenstoffverbindungen und die damit verbundenen Stoffumsaetze aufzuklaeren. An ausgewaehlten Geomatrizes wurde die Ausbildung von Oberflaechendepositen des NOM und deren Abhaengigkeit gegenueber geochemischen Parametern untersucht. Unter der Beruecksichtigung der Gegenwart von Hydroxyspezies und anorganischen Liganden wurde die Retention toxischer Schwermetalle an diesen Oberflaechendepositen des NOM untersucht. Die Untersuchungen zur Reaktivitaet der NOM-Spezies setzt eine Analytik dieser Verbindungen und der Schwermetalle im Ultraspurenbereich

  19. A Chiral Helical Compound Based on Achiral Components

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qi-Wei; WANG Gui-Xian


    The title compound, [Cu(dpa)(2,2'-bipy)(H2O)2]n 1 (H2dpa = diphenic acid and 2,2'- bipy = 2,2'-bipyridine), has been synthesized and its structure was determined by single-crystal X-ray diffraction. The crystal is of orthorhombic, space group P212121 with a = 10.597(4), b = 11.317(4), c = 17.630(7) (A), V = 2114.3(14)(A)3, C24H20CuN2O6, Mr = 495.97, Z = 4, Dc = 1.558 g/cm3, μ = 1.079 mm-1, F(000) = 1020, Flack value = 0.052(18), R = 0.0430 and wR = 0.1016 for 3381 observed reflections (Ⅰ > 2σ(Ⅰ)). In compound 1, the dpa ligands link metal ions into helical structures in the same direction.

  20. Carbohydrate-based bioactive compounds for medicinal chemistry applications. (United States)

    Cipolla, L; Peri, F


    In this article we review our work over the years on carbohydrates and carbohydrate mimetics and their applications in medicinal chemistry. In the first part of the review innovative synthetic methods, such as the chemoselective glycosylation method originally developed by our group and its applications to the synthesis of neoglycoconjugates (neoglycopeptides, oligosaccharide mimetics, neoglycolipids, etc…) will be presented. The high density of functional groups (hydroxyls) on the monosaccharides and the structural role of sugars forming the core of complex glycans in scaffolding and orienting the external sugar units for the interaction with receptors, inspired us and others to use sugars as scaffolds for the construction of pharmacologically active compounds. In the second part of this review, we will present some examples of bioactive and pharmacologically active compounds obtained by decorating monosaccharide scaffolds with pharmacophore groups. Sugar-derived protein ligands were also used as chemical probes to study the interaction of their target with other proteins in the cell. In this context, sugar mimetics and sugar-derived compounds have been employed as tools for exploring biology according to the "chemical genetic" approach.

  1. Influence of S. mutans on base-metal dental casting alloy toxicity. (United States)

    McGinley, E L; Dowling, A H; Moran, G P; Fleming, G J P


    We have highlighted that exposure of base-metal dental casting alloys to the acidogenic bacterium Streptococcus mutans significantly increases cellular toxicity following exposure to immortalized human TR146 oral keratinocytes. With Inductively Coupled Plasma-Mass Spectrometry (ICP-MS), S. mutans-treated nickel-based (Ni-based) and cobalt-chromium-based (Co-Cr-based) dental casting alloys were shown to leach elevated levels of metal ions compared with untreated dental casting alloys. We targeted several biological parameters: cell morphology, viable cell counts, cell metabolic activity, cell toxicity, and inflammatory cytokine expression. S. mutans-treated dental casting alloys disrupted cell morphology, elicited significantly decreased viable cell counts (p S. mutans-treated Ni-based dental casting alloys induced elevated levels of cellular toxicity compared with S. mutans-treated Co-Cr-based dental casting alloys. While our findings indicated that the exacerbated release of metal ions from S. mutans-treated base-metal dental casting alloys was the likely result of the pH reduction during S. mutans growth, the exact nature of mechanisms leading to accelerated dissolution of alloy-discs is not yet fully understood. Given the predominance of S. mutans oral carriage and the exacerbated cytotoxicity observed in TR146 cells following exposure to S. mutans-treated base-metal dental casting alloys, the implications for the long-term stability of base-metal dental restorations in the oral cavity are a cause for concern.

  2. Toxicity of Methylated Bismuth Compounds Produced by Intestinal Microorganisms to Bacteroides thetaiotaomicron, a Member of the Physiological Intestinal Microbiota

    Directory of Open Access Journals (Sweden)

    Beatrix Bialek


    Full Text Available Methanoarchaea have an outstanding capability to methylate numerous metal(loids therefore producing toxic and highly mobile derivatives. Here, we report that the production of methylated bismuth species by the methanoarchaeum Methanobrevibacter smithii, a common member of the human intestine, impairs the growth of members of the beneficial intestinal microbiota at low concentrations. The bacterium Bacteroides thetaiotaomicron, which is of great importance for the welfare of the host due to its versatile digestive abilities and its protective function for the intestine, is highly sensitive against methylated, but not against inorganic, bismuth species. The level of methylated bismuth species produced by the methanoarchaeum M. smithii in a coculture experiment causes a reduction of the maximum cell density of B. thetaiotaomicron. This observation suggests that the production of methylated organometal(loid species in the human intestine, caused by the activity of methanoarchaea, may affect the health of the host. The impact of the species to reduce the number of the physiological intestinal microbiota brings an additional focus on the potentially harmful role of methanoarchaea in the intestine of a higher organism.

  3. Toxicity and hazardous properties of solvent base adhesive wastes. (United States)

    Sabater, M C; Martínez, M A; Font, R


    In this work, the hazardous properties of solvent base adhesive wastes generated in the footwear manufacturing process have been studied. The characterisation procedures and criteria used are those contained in the legal documents European Union Council Decision 94/904/CE and October 13th Spanish Ministerial Order. The properties studied were the following: flash point, reactivity (gas generation), ecotoxicity, main contaminants extracted by the leaching process and main harmful substances contained in wastes. An additional study of the relationship between flash point and solvent concentration in waste was carried out for polyurethane-acetone and neoprene-toluene systems. The wastes considered were metal containers with remains of dry or semi-dry adhesive. The results obtained show that the presence of solvent in wastes confers on them hazardous characteristics (flash point and harmful composition) depending on the solvent type and its concentration.

  4. A new group contribution-based model for estimation of lower flammability limit of pure compounds. (United States)

    Gharagheizi, Farhad


    In the present study, a new method is presented for estimation of lower flammability limit (LFL) of pure compounds. This method is based on a combination of a group contribution method and neural networks. The parameters of the model are the occurrences of a new collection of 105 functional groups. Basing on these 105 functional groups, a feed forward neural network is presented to estimate the LFL of pure compounds. The average absolute deviation error obtained over 1057 pure compounds is 4.62%. Therefore, the model is an accurate model and can be used to predict the LFL of a wide range of pure compounds.


    LoPachin, Richard M.; Gavin, Terrence; DeCaprio, Anthony; Barber, David S.


    Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are however discriminatory, since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acid and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this Perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic

  6. Application of the Hard and Soft, Acids and Bases (HSAB) theory to toxicant--target interactions. (United States)

    Lopachin, Richard M; Gavin, Terrence; Decaprio, Anthony; Barber, David S


    Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are, however, discriminatory since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acids and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic

  7. Effects of solvents and dosing procedure on chemical toxicity in cell-based in vitro assays.

    NARCIS (Netherlands)

    Tanneberger, K.; Rico Rico, A.; Kramer, N.I.; Busser, F.J.M.; Hermens, J.L.M.; Schirmer, K.


    Due to the implementation of new legislation, such as REACh, a dramatic increase of animal use for toxicity testing is expected and the search for alternatives is timely. Cell-based in vitro assays are promising alternatives. However, the behavior of chemicals in these assays is still poorly underst

  8. Studies on the Quantitative Structure-activity Relationship of Toxicity of Chlorophenol Serial Compounds in the ab initio Methods and Substitutive Position of Chlorine Atom (NPCS)

    Institute of Scientific and Technical Information of China (English)

    ZHENG Qing; WANG Lian-Sheng


    20 Quantum chemical parameters of chlorophenol compounds were fully optimized by using B3LYP method on both 6-31G* and 6-311G* basis sets. These structural parameters are taken as theoretical descriptors, and the experimental data of 20 compounds' aquatic photogen toxicity(-1gEC50) are used to perform stepwise regression in order to obtain two predicted -lgEC50 correlation models whose correlation coefficients R2 are respectively 0.9186 and 0.9567. In addition, parameters of chlorine atom's substitutive positions and their correlations (NPCs) are taken as descriptors to obtain another predicted -1gEC50 model with the correlation coefficient R2 of 0.9444. Correlation degree of each independent variable in the three models is verified by using variance inflation factors (VIF) and t value. In the cross-validation method, cross-validation coefficients q2 of 3 models are respectively 0.8748, 0.9119 and 0.8993, which indicates that the relativity and prediction ability of this model are superior to those of the model obtained by topological and BLYP methods.

  9. Nonlinear dimensionality reduction for visualizing toxicity data: distance-based versus topology-based approaches. (United States)

    Kireeva, Natalia V; Ovchinnikova, Svetlana I; Tetko, Igor V; Asiri, Abdullah M; Balakin, Konstantin V; Tsivadze, Aslan Yu


    Over the years, a number of dimensionality reduction techniques have been proposed and used in chemoinformatics to perform nonlinear mappings. In this study, four representatives of nonlinear dimensionality reduction methods related to two different families were analyzed: distance-based approaches (Isomap and Diffusion Maps) and topology-based approaches (Generative Topographic Mapping (GTM) and Laplacian Eigenmaps). The considered methods were applied for the visualization of three toxicity datasets by using four sets of descriptors. Two methods, GTM and Diffusion Maps, were identified as the best approaches, which thus made it impossible to prioritize a single family of the considered dimensionality reduction methods. The intrinsic dimensionality assessment of data was performed by using the Maximum Likelihood Estimation. It was observed that descriptor sets with a higher intrinsic dimensionality contributed maps of lower quality. A new statistical coefficient, which combines two previously known ones, was proposed to automatically rank the maps. Instead of relying on one of the best methods, we propose to automatically generate maps with different parameter values for different descriptor sets. By following this procedure, the maps with the highest values of the introduced statistical coefficient can be automatically selected and used as a starting point for visual inspection by the user.

  10. NMR-based metabonomic study on the subacute toxicity of aristolochic acid in rats. (United States)

    Zhang, Xiaoyu; Wu, Huifeng; Liao, Peiqiu; Li, Xiaojing; Ni, Jiazuan; Pei, Fengkui


    The subacute toxicity of aristolochic acid (AA) was investigated by (1)H NMR spectroscopic and pattern recognition (PR)-based metabonomic methods. Model toxins were used to enable comparisons of the urinary profiles from rats treated with known toxicants and AA at various time intervals. Urinary (1)H NMR spectra were data-processed and analyzed by pattern recognition method. The result of visual comparison of the spectra showed that AA caused a renal proximal tubular and papillary lesion and a slight hepatic impair. Pattern recognition analysis indicated that the renal proximal tubule lesion was the main damage induced by AA, and the renal toxicity induced by AA was a progressive course with the accumulation of dosage by monitoring the toxicological processes from onset, development and part-recovery. These results were also supported by the conventional clinical biochemical parameters.

  11. In Vitro and In Vivo toxicity profiling of ammonium-based deep eutectic solvents. (United States)

    Hayyan, Maan; Looi, Chung Yeng; Hayyan, Adeeb; Wong, Won Fen; Hashim, Mohd Ali


    The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDESIn Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes.

  12. [Fatal toxic leukoencephalopathy associated with consumption of pasta base of cocaine: Report of three cases]. (United States)

    Cartier R, Luis; González L, Daniela; Harán D, Jorge


    The prevalence of drug-associated toxic encephalopathy is unknown, but it is an uncommon condition. Toxic leukoencephalopathy was described associated with heroin consumption, it has been less commonly described with the use of cocaine and there are no reports of its association with consumption pasta base of cocaine (PBC). We report two females aged 31 years and a male aged 19 years, consumers of PBC who developed a fatal toxic leukoencephalopathy. They initiated their disease with severe and persistent headache, sequential focal neurologic deficits and a progressive impairment of consciousness that culminated with their death. Laboratory parameters such as blood count, cerebrospinal fluid analyses or infectious biological indices were normal. MRI showed multifocal lesions in brain white matter of both hemispheres confirming the leukoencephalopathy. There was no response to the use of methylprednisolone.

  13. Nanosuspension formulations of poorly water-soluble compounds for intravenous administration in exploratory toxicity studies: in vitro and in vivo evaluation. (United States)

    Fujimura, Hisako; Komasaka, Takao; Tomari, Taizo; Kitano, Yasunori; Takekawa, Kouji


    This study was conducted to investigate the use of a nanosuspension for intravenous injection into dogs to increase exposure without toxic additives for preclinical studies in the discovery stage. Nanosuspensions were prepared with a mixer mill and zirconia beads with a vehicle of 2% (w/v) poloxamer 338, which was confirmed to lead to no histamine release in dogs. Sterilized nanosuspensions of poorly water-soluble compounds, cilostazol (Cil), spironolactone (Spi) and probucol (Pro), at 10 mg ml(-1) were obtained by milling for 30 min, followed by autoclaving for 20 min at 121 °C and milling for 30 min (mill-autoclave-mill method). The particle sizes (d50) of Cil, Spi and Pro were 0.554, 0.484 and 0.377 µm, respectively, and the percentages of the nominal concentration were 79.1%, 99.6% and 75.4%, respectively. In chromatographic data, no extra peaks were observed. The particle size of Cil was 0.564 µm after storage for 16 days at 2-8 °C. Cil in nanosuspension, but not in microsuspension, rapidly dissolved in dog plasma. Cil nanosuspension at 0.4 mg kg(-1) and Cil saline solution at 0.03 mg kg(-1) , around the saturation solubility, were intravenously administered to dogs. Nanosuspension increased exposure. The versatility of the mill-autoclave-mill method was checked for 15 compounds, and the particle size of 12 compounds was in the nano range. The nanosuspension optimized in this study may be useful for intravenous toxicological and pharmacological studies in the early stage of drug development. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Natural Hg isotopic composition of different Hg compounds in mammal tissues as a proxy for in vivo breakdown of toxic methylmercury. (United States)

    Perrot, Vincent; Masbou, Jeremy; Pastukhov, Mikhail V; Epov, Vladimir N; Point, David; Bérail, Sylvain; Becker, Paul R; Sonke, Jeroen E; Amouroux, David


    In the last decade, specific attention has been paid to total mercury (HgT) stable isotopic composition, especially in natural samples such as aquatic organisms, due to its potential to track the cycle of this toxic element in the environment. Here, we investigated Hg Compound Specific stable Isotopic Composition (CSIC) of natural inorganic Hg (iHg) and methylmercury (MMHg) in various tissues of aquatic mammals (Beluga whale from the Arctic marine environment and seals from the freshwater lake Baikal, Russia). In seals' organs the variation in mass dependent fractionation (MDF, δ(202)Hg) for total Hg was significantly correlated to the respective fraction of iHg and MMHg compounds, with MMHg being enriched by ∼ 3‰ in heavier isotopes relative to iHg. On the other hand, we observe insignificant variation in Hg mass independent isotope fractionation (MIF, Δ(199)Hg) among iHg and MMHg in all organs for the same mammal species and MMHg in prey items. MIF signatures suggest that both MMHg and iHg in aquatic mammals have the same origin (i.e., MMHg from food), and are representative of Hg photochemistry in the water column of the mammal ecosystem. MDF signatures of Hg compounds indicate that MMHg is demethylated in vivo before being stored in the muscle, and the iHg formed is stored in the liver, and to a lesser extent in the kidney, before excretion. Thus, Hg CSIC analysis in mammals can be a powerful tool for tracing the metabolic response to Hg exposure.

  15. Building Asphalt Pavement with SBS-based Compound Added Using a Dry Process in Greenland

    DEFF Research Database (Denmark)

    Lee, Hosin; Kim, Yongjoo; Geisler, Nivi


    heavy traffic and severe weather conditions in Greenland. Based on the initial set of strain data collected under the slow-moving loader right after construction, the highest strain value was observed from the test section with the highest amount of SBS-based compound. The increased amount of SBS......-based compound seemed to affect the asphalt mix to become more flexible under the heavy loads. By adding SBS-based compound to asphalt mixtures using a “dry” process, it is expected that the pavement would become more resistant to rutting than a typical asphalt mixture used in Greenland while enduring its arctic...... weather....

  16. Spectroscopic and structural investigation on intermediates species structurally associated to the tricyclic bisguanidine compound and to the toxic agent, saxitoxin (United States)

    Romani, Davide; Tsuchiya, Shigeki; Yotsu-Yamashita, Mari; Brandán, Silvia Antonia


    In the present work, we have studied the structural, topological and spectroscopic properties of five cyclic and of open chain species derived from tricyclic bisguanidine compound in gas and aqueous phases combining the DFT calculations with the experimental infrared and 1H NMR, 13C NMR and UV-visible spectra. These species are members of the saxitoxin family and they were recently synthesized by Tsuchiya et al. (Chemistry. A European Journal, 21 (2015) 7835-7840). Here, the self consistent reaction force (SCRF) calculations were employed in aqueous medium to study the solvation energies by using the polarized continuum (PCM) and solvation (SM) models. All the calculations were performed with the 6-31G* and 6-311++G** basis sets. The atomic charges, electrostatic potentials, bond order, stabilization energy, topological properties suggest the structural connection between the cyclic cationic and saxitoxin species while the electrophilicity and nucleophilicity indexes could be one of the explanations for the Nav blocking activities of these species. The complete vibrational assignments for all the species are reported. The predicted spectra present a reasonable concordance with the corresponding experimental ones.

  17. Increased toxicity of a trinuclear Pt-compound in a human squamous carcinoma cell line by polyamine depletion

    Directory of Open Access Journals (Sweden)

    Kjellström Johan


    Full Text Available Abstract Background Mononuclear platinum anticancer agents hold a pivotal place in the treatment of many forms of cancers, however, there is a potential to improve response to evade resistance development and toxic side effects. BBR3464 is a promising trinuclear platinum anticancer agent, which is a polyamine mimic. The aim was to investigate the influence of polyamine pool reduction on the cytotoxic effects of the trinuclear platinum complex BBR3464 and cisplatin. Polyamine pool reduction was achieved by treating cells with either the polyamine biosynthesis inhibitor α-difluoromethylornithine (DFMO or the polyamine analogue N1,N11-diethylnorspermine (DENSPM. Methods A human squamous cell carcinoma cell line, LU-HNSCC-4, established from a primary head and neck tumour was used to evaluate cellular effects of each drug alone or combinations thereof. High-performance liquid-chromatography was used to quantify intracellular polyamine contents. Inductively coupled mass spectroscopy was used to quantify intracellular platinum uptake. Cells were exposed to DFMO or DENSPM during 48 h at concentrations ranging from 0 to 5 mM or 0 to 10 μM, respectively. Thereafter, non-treated and treated cells were exposed to cisplatin or BBR3464 during 1 h at concentrations ranging from 0 to 100 μM. A 96-well assay was used to determine cytotoxicity after five days after treatment. Results The cytotoxic effect of BBR3464 on LU-HNSCC-4 cells was increased after cells were pre-treated with DENSPM or DFMO, and the interaction was found to be synergistic. In contrast, the interaction between cisplatin and DFMO or DENSPM was near-additive to antagonistic. The intracellular levels of the polyamines putrescine and spermidine were decreased after treatment with DFMO, and treatment with DENSPM resulted in an increase in putrescine level and concomitant decrease in spermidine and spermine levels. The uptake of BBR3464 was significantly increased after pre

  18. 一种复方苯扎溴铵消毒剂的毒效应研究%Research on Toxic Effects of a Compound Benzalkonium Bromide Disinfectant

    Institute of Scientific and Technical Information of China (English)

    李立; 尹晓晨; 胡余明


    Objective To study the toxic effects of a compound benzalkonium bromide disinfectant and to investigate the bio- safety of the use of benzalkonium bromide as a disinfectant. Methods Acute oral toxicity, repeated skin irritation test, once damaged skin irritation test, micronucleus test and subacute toxicity test were conducted. Results The acute oral LD50 of the test substance in male and female Kunming mice was greater than 5,000 mg/kg·bw. The compound benzalkonium bromide disinfectant produced no irritation on intact skin and injured skin of rabbits. The result of the mouse bone marrow cell micronucleus test was negative. In the subacute toxicity test, after 28 d oral administration of the test .substance, the growth and development of the rats in each dose group were good. The body weight gain, indexes of the routine blood test and blood biochemical test showed no significant difference between rats in each dose group and the control group. The main organs of the experimental animals showed no obvious pathological changes. Conclusions In this experiment condition, the acute oral toxicity of the compound benzalkonium bromide disinfectant is at the actual non - toxic level. Skin irritation tests show it is a non - irritant substance. The result of the mouse bone marrow cell micronucleus test is negative. It does not produce subacute toxicity in rats. The results suggest that the normal use of the disinfectant is safe.%目的 研究一种复方苯扎溴铵消毒剂的毒性效应,了解苯扎溴铵作为消毒剂使用的生物安全性.方法 采用急性经口毒性、多次完整皮肤刺激试验、一次破损皮肤刺激试验、微核试验和亚急性毒性试验进行观察.结果 本研究中昆明种雌、雄小鼠的急性经口LD50均大于5000 mg/kg·bw;在兔多次完整皮肤刺激试验中,复方苯扎溴铵消毒剂多次接触动物完整皮肤未引起动物皮肤刺激反应;在兔一次破损皮肤刺激试验中,对白色家兔的皮肤无

  19. Cyclodextrin-based microsensors for volatile organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, B.; Johnson, S.; Shi, J.; Yang, Xiaoguang


    Host-guest chemistry and self-assembly techniques are being explored to develop species selective thin-films for real-time sensing of volatile organic compounds (VOCs). Cyclodextrin (CD) and calixarene (CA) molecules are known to form guest-host inclusion complexes with a variety of organic molecules. Through the control of the cavity size and chemical functionality on the rims of these bucket-like molecules, the binding affinities for formation of inclusion complexes can be controlled and optimized for specific agents. Self-assembly techniques are used to covalently bond these reagent molecules to the surface of acoustic transducers to create dense, highly oriented, and stable thin films. Self-assembly techniques have also been used to fabricate multilayer thin film containing molecular recognition reagents through alternating adsorption of charged species in aqueous solutions. Self-assembly of polymeric molecules of the SAW device was also explored for fabricating species selective interfaces.

  20. Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction. (United States)

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


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

  1. Synthesis of Tetra-Schiff Base Macrocyclic Compound Containing Benzo-12-crown-4

    Institute of Scientific and Technical Information of China (English)


    Tetra-Schiff base macrocyclic compound containing benzo-12-crown-4 was synthesized via condensation of 2, 6-diformyl-4-methyl-phenol with 4(, 5(- diaminobenzo-12-C- 4 promoted by proton. The compound was characterized by MS, IR 1HNMR spectroscopy and elemental analysis.

  2. A specific gas chromatographic detector for carbonyl compounds, based on polarography. (United States)

    Fleet, B; Risby, T H


    The evaluation of a specific gas Chromatographie detector for carbonyl compounds is described. This is based on the polarographic reduction of the Girard T hydrazone derivative which is formed when the carbonyl compound is absorbed in a buffered supporting electrolyte containing the carbonyl reagent. The detector was used to monitor the separation of a homologous series of alkanals.

  3. A spheroid toxicity assay using magnetic 3D bioprinting and real-time mobile device-based imaging. (United States)

    Tseng, Hubert; Gage, Jacob A; Shen, Tsaiwei; Haisler, William L; Neeley, Shane K; Shiao, Sue; Chen, Jianbo; Desai, Pujan K; Liao, Angela; Hebel, Chris; Raphael, Robert M; Becker, Jeanne L; Souza, Glauco R


    An ongoing challenge in biomedical research is the search for simple, yet robust assays using 3D cell cultures for toxicity screening. This study addresses that challenge with a novel spheroid assay, wherein spheroids, formed by magnetic 3D bioprinting, contract immediately as cells rearrange and compact the spheroid in relation to viability and cytoskeletal organization. Thus, spheroid size can be used as a simple metric for toxicity. The goal of this study was to validate spheroid contraction as a cytotoxic endpoint using 3T3 fibroblasts in response to 5 toxic compounds (all-trans retinoic acid, dexamethasone, doxorubicin, 5'-fluorouracil, forskolin), sodium dodecyl sulfate (+control), and penicillin-G (-control). Real-time imaging was performed with a mobile device to increase throughput and efficiency. All compounds but penicillin-G significantly slowed contraction in a dose-dependent manner (Z' = 0.88). Cells in 3D were more resistant to toxicity than cells in 2D, whose toxicity was measured by the MTT assay. Fluorescent staining and gene expression profiling of spheroids confirmed these findings. The results of this study validate spheroid contraction within this assay as an easy, biologically relevant endpoint for high-throughput compound screening in representative 3D environments.

  4. Translation of Japanese Noun Compounds at Super-Function Based MT System (United States)

    Zhao, Xin; Ren, Fuji; Kuroiwa, Shingo

    Noun compounds are frequently encountered construction in nature language processing (NLP), consisting of a sequence of two or more nouns which functions syntactically as one noun. The translation of noun compounds has become a major issue in Machine Translation (MT) due to their frequency of occurrence and high productivity. In our previous studies on Super-Function Based Machine Translation (SFBMT), we have found that noun compounds are very frequently used and difficult to be translated correctly, the overgeneration of noun compounds can be dangerous as it may introduce ambiguity in the translation. In this paper, we discuss the challenges in handling Japanese noun compounds in an SFBMT system, we present a shallow method for translating noun compounds by using a word level translation dictionary and target language monolingual corpus.

  5. Integrating in vitro data and physiologically based kinetic (PBK) modelling to assess the in vivo potential developmental toxicity of a series of phenols. (United States)

    Strikwold, Marije; Spenkelink, Bert; de Haan, Laura H J; Woutersen, Ruud A; Punt, Ans; Rietjens, Ivonne M C M


    Toxicity outcomes derived in vitro do not always reflect in vivo toxicity values, which was previously observed for a series of phenols tested in the embryonic stem cell test (EST). Translation of in vitro data to the in vivo situation is therefore an important, but still limiting step for the use of in vitro toxicity outcomes in the safety assessment of chemicals. The aim of the present study was to translate in vitro embryotoxicity data for a series of phenols to in vivo developmental toxic potency values for the rat by physiologically based kinetic (PBK) modelling-based reverse dosimetry. To this purpose, PBK models were developed for each of the phenols. The models were parameterised with in vitro-derived values defining metabolism and transport of the compounds across the intestinal and placental barrier and with in silico predictions and data from the literature. Using PBK-based reverse dosimetry, in vitro concentration-response curves from the EST were translated into in vivo dose-response curves from which points of departure (PoDs) were derived. The predicted PoDs differed less than 3.6-fold from PoDs derived from in vivo toxicity data for the phenols available in the literature. Moreover, the in vitro PBK-based reverse dosimetry approach could overcome the large disparity that was observed previously between the in vitro and the in vivo relative potency of the series of phenols. In conclusion, this study shows another proof-of-principle that the in vitro PBK approach is a promising strategy for non-animal-based safety assessment of chemicals.

  6. Radiation effects on II-VI compound-based detectors

    CERN Document Server

    Cavallini, A; Dusi, W; Auricchio, N; Chirco, P; Zanarini, M; Siffert, P; Fougeres, P


    The performance of room temperature CdTe and CdZnTe detectors exposed to a radiation source can be strongly altered by the interaction of the ionizing particles and the material. Up to now, few experimental data are available on the response of II-VI compound detectors to different types of radiation sources. We have carried out a thorough investigation on the effects of gamma-rays, neutrons and electron irradiation both on CdTe : Cl and Cd sub 0 sub . sub 9 Zn sub 0 sub . sub 1 Te detectors. We have studied the detector response after radiation exposure by means of dark current measurements and of quantitative spectroscopic analyses at low and medium energies. The deep traps present in the material have been characterized by means of PICTS (photo-induced current transient spectroscopy) analyses, which allow to determine the trap apparent activation energy and capture cross-section. The evolution of the trap parameters with increasing irradiation doses has been monitored for all the different types of radiati...

  7. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologycally based kinetic modeling

    NARCIS (Netherlands)

    Louisse, J.; Bosgra, S.; Blaauboer, B.J.; Rietjens, I.; Verwei, M.


    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity d

  8. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologically based kinetic modeling

    NARCIS (Netherlands)

    Louisse, Jochem; Bosgra, Sieto; Blaauboer, Bas J.; Rietjens, Ivonne M. C. M.; Verwei, Miriam


    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity d

  9. Prediction of in vivo developmental toxicity of all-trans-retinoic acid based on in vitro toxicity data and in silico physiologically based kinetic modeling

    NARCIS (Netherlands)

    Louisse, J.; Bosgra, S.; Blaauboer, B.J.; Rietjens, I.M.C.M.; Verwei, M.


    The use of laboratory animals for toxicity testing in chemical safety assessment meets increasing ethical, economic and legislative constraints. The development, validation and application of reliable alternatives for in vivo toxicity testing are therefore urgently needed. In order to use toxicity

  10. Design of an activity landscape view taking compound-based feature probabilities into account. (United States)

    Zhang, Bijun; Vogt, Martin; Bajorath, Jürgen


    Activity landscapes (ALs) of compound data sets are rationalized as graphical representations that integrate similarity and potency relationships between active compounds. ALs enable the visualization of structure-activity relationship (SAR) information and are thus computational tools of interest for medicinal chemistry. For AL generation, similarity and potency relationships are typically evaluated in a pairwise manner and major AL features are assessed at the level of compound pairs. In this study, we add a conditional probability formalism to AL design that makes it possible to quantify the probability of individual compounds to contribute to characteristic AL features. Making this information graphically accessible in a molecular network-based AL representation is shown to further increase AL information content and helps to quickly focus on SAR-informative compound subsets. This feature probability-based AL variant extends the current spectrum of AL representations for medicinal chemistry applications.

  11. Application of a lux-based bioassay to assess soil toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Paton, G.I. [Macaulay Land Use Research Inst., Aberdeen (United Kingdom)]|[Univ. of Aberdeen (United Kingdom); Campbell, C.D. [Macaulay Land Use Research Inst., Aberdeen (United Kingdom); Rattray, E.A.S.; Glover, L.A.; Killham, K. [Univ. of Aberdeen (United Kingdom)


    The expression of prokaryotic bioluminescence is linked with cell metabolism and accordingly bioassays have been developed using naturally bioluminescent bacteria to assess ecotoxicity. Advances in biotechnology have allowed the isolation of the lux genes (responsible for bioluminescence) from marine organisms and their insertion into terrestrial bacteria. This has enabled the use of ecologically relevant bacteria to assess toxicity by measuring bioluminescence response in the presence of toxins. The lux genes were inserted into Pseudomonas fluorescens and Rhizobium leguminosarum biovar trifolii as a multi-copy plasmid and also integrated into the chromosome. It was found that in aqueous solutions the plasmid constructs were more sensitive than the chromosomal constructs to a range of toxins. The order of toxicity for Ps. fluorescens was Zn = Cu > Cd > Ni > Cr > DCP and for R. trifolii Zn > Cu > Cd > DCP > Cr. The lux based bioassays were more reproducible and sensitive than ATP and dehydrogenase assays and offered greater sensitivity than Photobacterium phosphoreum assays to assess toxicity of inorganic pollutants. Extracts from 4 soil types were spiked with a range of toxins and when EC{sub 50} values were determined it was shown that toxicity was related to soil characteristics. This enabled the assay to be used to assess the Lee Valley soil experiment which represents an important international study of the effect of the application of contaminated sewage to land. High metal application rates had been shown to have serious implications for soil ecology. Chemical analysis, carried out 26 years after sewage addition confirmed that soil extracts still had increased metal concentrations. The lux-based bioassays, which proved to be rapid, reproducible and sensitive confirmed that the metals were still biologically available and hence toxic.

  12. Screening the Emission Sources of Volatile Organic Compounds (VOCs) in China Based on Multi-effect Evaluation (United States)

    Niu, H., Jr.


    Volatile organic compounds (VOCs) in the atmosphere have adverse impacts via three main pathways: photochemical ozone formation, secondary organic aerosol production, and direct toxicity to humans. Few studies have integrated these effects to prioritize control measures for VOCs sources. In this study, we developed a multi-effect evaluation methodology based on updated emission inventories and source profiles, which was combined with ozone formation potential (OFP), secondary organic aerosol potential (SOAP), and VOC toxicity data to identify important emission sources and key species. We derived species-specific emission inventories for 152 sources. The OFPs, SOAPs, and toxicity of each source were determined, and the contribution and share of each source to each of these adverse effects was calculated. Weightings were given to the three adverse effects by expert scoring, and the integrated impact was determined. Using 2012 as the base year, solvent usage and industrial process were found to be the most important anthropogenic sources, accounting for 24.2 and 23.1% of the integrated environmental effect, respectively. This was followed by biomass burning, transportation, and fossil fuel combustion, all of which had a similar contribution ranging from 16.7 to 18.6%. The top five industrial sources, including plastic products, rubber products, chemical fiber products, the chemical industry, and oil refining, accounted for nearly 70.0% of industrial emissions. In China, emissions reductions are required for styrene, toluene, ethylene, benzene, and m/p-xylene. The 10 most abundant chemical species contributed 76.5% of the integrated impact. Beijing, Chongqing, Shanghai, Jiangsu, and Guangdong were the five leading provinces when considering the integrated effects. Besides, the chemical mass balance model (CMB) was used to verify the VOCs inventories of 47 cities in China, so as to optimize our evaluation results. We suggest that multi-effect evaluation is necessary to

  13. Molecular docking and ADME-toxicity studies of potential compounds of medicinal plants grown in Indonesia as an anti-rheumatoid arthritis (United States)

    Awaluddin, Rizki; Muhtadi, Wildan Khairi; Chabib, Lutfi; Ikawati, Zullies; Martien, Ronny; Ismail, Hilda


    Rheumatoid arthritis (RA) is an autoimmune disease with recurrent bone destruction around the joints that could lead to permanent joint damage. DMARDs (Disease Modifying Anti-Rheumatoid Drugs) and NSAIDs (Non-Steroid Anti-Inflammatory Drugs) are the RA therapies with many side effects on long term use. Based on the ethnomedicine, there are many plants that could be found in Indonesia that contain the potential compounds as alternative RA therapies. The aim of this study is to assess the potential of compounds of various medicinal plants against multiple proteins that play an important role on RA through the molecular docking study and pharmacokinetic prediction. Hesperidin, EGCG (Epigallocatechin gallate), and mangiferin showed higher activity compared to the other compounds against TACE (TNF-α converting enzyme) which play an important role in the inhibition of TNF-α. Inhibition on it could suppress macrophage cell and T-cell activity by suppressing the regulation of cytokine secretion against inflammation. Furthermore, hesperidin, EGCG, and mangiferin did not show effects on CYP450 (cytochrome P450). Modification of drug delivery system must be done to increase the bioavailability of the compounds. It can be concluded that hesperidin, EGCG, and mangiferin are potential to be developed as an RA therapy with a modification of drug delivery system. This study suggest the encapsulation method using liposome as the drug carrier, which is suitable with the charactheristic of hesperidine, EGCG, and mangiferin.

  14. Modelling of the Kinetics of Sulfure Compounds in Desulfurisation Processes Based on Industry Data of Plant

    Directory of Open Access Journals (Sweden)

    Krivtcova Nadezhda


    Full Text Available Modelling of sulfur compounds kinetics was performed, including kinetics of benzothiophene and dibenzothiophene homologues. Modelling is based on experimental data obtained from monitoring of industrial hydrotreating set. Obtained results include kinetic parameters of reactions.

  15. Green chemistry approach to the synthesis of potentially bioactive aminobenzylated Mannich bases through active hydrogen compounds

    Directory of Open Access Journals (Sweden)

    S. L. VASOYA


    Full Text Available An efficient and high yield method for the synthesis of aminobenzylated Mannich bases is described. The synthesis occurs in aqueous medium at 0 ºC. The compounds show moderate antitubercular and antimicrobial activities.

  16. Nuclear magnetic resonance on selected lithium based compounds

    Energy Technology Data Exchange (ETDEWEB)

    Rudisch, Christian


    This thesis presents the NMR measurements on the single crystals LiMnPO{sub 4} and Li{sub 0.9}FeAs. Therefore, the thesis is divided into two separated sections. The first part reports on the competitive next generation cathode material LiMnPO{sub 4} with a stable reversible capacity up to 145 mAh/g and a rather flat discharge voltage curve at 4.1 V. For the basic understanding of the material the magnetic properties have been investigated by a Li and P NMR study in the paramagnetic and antiferromagnetic phase. LiMnPO{sub 4} shows a strong anisotropy of the dipolar hyperfine coupling due to the strong local magnetic moments at the Mn site. The corresponding dipole tensor of the Li- and P-nuclei is fully determined by orientation and temperature dependent NMR experiments and compared to the calculated values from crystal structure data. Deviations of the experimentally determined values from the theoretical ones are discussed in terms of Mn disorder which could have an impact on the mobility of the Li ions. The disorder is corroborated by diffuse X-ray diffraction experiments which indicate a shift of the heavy elements in the lattice, namely the Mn atoms. Furthermore, the spin arrangement in the relative strong field of 7.0494 T in the antiferromagnetic state is understood by the NMR measurements. In order to obtain parameters of the Li ion diffusion in LiMnPO{sub 4} measurements of the spin lattice relaxation rate were performed. Due to the strong dipolar coupling between the Li-nuclei and the magnetic moments at the Mn site it is difficult to extract parameters which can characterize the diffusive behavior of the Li ions. The second section reports on the AC/DC susceptibility and NMR/NQR studies on Li deficit samples labeled as Li{sub 0.9}FeAs. LiFeAs belongs to the family of the superconducting Pnictides which are discovered in 2008 by H. Hosono et al. In recent studies the stoichiometric compound reveals triplet superconductivity below T{sub c}-18 K which

  17. Advances in the development and use of human tissue-based techniques for drug toxicity testing. (United States)

    Clotworthy, Margaret; Archibald, Kathy


    Unacceptable failure rates in clinical trials are largely responsible for the high costs of bringing successful drugs to market - costs that are passed on to patients, insurers or healthcare providers. Furthermore, failures in clinical trials deny patients much-needed new drugs and potentially expose them to unnecessary risk. With so many medicines reaching their patent expiry date, pressure is on the pharmaceutical industry to not only increase its output of effective medicines but also improve its ability to minimise safety issues. This review focuses on the availability and use of human tissues and their derivatives to explore potential toxicity problems of new drugs. The growth in the number and quality of human material-based assays and enabling technologies is reviewed, followed by a discussion of the application of such assays to identify specific toxicities, using specific examples. Although human tissues are now beginning to be seen as playing an important role in evaluating the potential for toxicity of new drugs in the clinic, their importance deserves to be more widely recognised and their use in the identification of toxicity issues as early as possible in the drug development life cycle should be significantly increased.

  18. Antimonide-Based Compound Semiconductors for Electronic Devices: A Review (United States)


    currents, apparently due to exten- sive interface recombination [137]. Dodd et al. fabricated npn InAs bipolar transistors on InP in an attempt to achieve...Demonstration of npn InAs bipolar transistors with inverted base doping. IEEE Electron Dev Lett 1996;17(4):166–8. [139] Moran PD, Chow D, Hunter A, Kuech TF...based electronic devices: high electron mobility transistors (HEMTs), resonant tunneling diodes (RTDs), and heterojunction bipolar transistors (HBTs

  19. Toxicity and Larvicidal Activity of Podophyllum-Based Lignans Against Aedes aegypti (Diptera: Culicidae). (United States)

    Maleck, Marise; Hollanda, Priscila de Oliveira; Serdeiro, Michele Teixeira; Soares, Renata Oliveira de Araújo; Honório, Nildimar Alves; Silva, Cláudia Gontijo


    Aedes aegypti L. (Diptera: Culicidae) is a mosquito species that has adapted to urban environments and is the main vector of dengue viruses. Because of the increasing incidence of dengue, a more environmentally acceptable insecticide needs to be found. Natural products have been and continue to be an important source of leading compounds that can be modified in order to develop new drugs. The lignan family of natural products includes compounds with a diverse spectrum of biological activity. Podophyllotoxin and its related lignans represent an exciting class of natural products that can be targeted at different types of biological activity and are therefore worth exploring further. This study had the aim of evaluating the larvicidal activity of an ethanolic extract from the rhizomes and roots of Podophyllum hexandrum (PM-3) and its isolated lignans, podophyllotoxone (1) and desoxypodophyllotoxin (2), on the larvae of the mosquito vector Ae. aegypti. The PM-3 extract and the compounds (1) and (2) were dissolved in a mixture of acetone and dimethylsulfoxide at final concentrations of 1, 10, 30, 50, 100, and 200 μg/ml. After dilution, the solutions were applied (μg/ml) to the larvae-rearing medium. Overall, the ethanolic extract from the rhizomes and roots of P. hexandrum and the compounds (1) and (2) showed larvicidal activity against the larvae of Ae. aegypti According to the results from this study, it can be concluded that podophyllotoxone (1) and desoxypodophyllotoxin (2) exhibited significant toxicity toward Ae. aegypti larvae. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email:

  20. Determination of sulfur compounds in hydrotreated transformer base oil by potentiometric titration. (United States)

    Chao, Qiu; Sheng, Han; Cheng, Xingguo; Ren, Tianhui


    A method was developed to analyze the distribution of sulfur compounds in model sulfur compounds by potentiometric titration, and applied to analyze hydrotreated transformer base oil. Model thioethers were oxidized to corresponding sulfoxides by tetrabutylammonium periodate and sodium metaperiodate, respectively, and the sulfoxides were titrated by perchloric acid titrant in acetic anhydride. The contents of aliphatic thioethers and total thioethers were then determined from that of sulfoxides in solution. The method was applied to determine the organic sulfur compounds in hydrotreated transformer base oil.

  1. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium (United States)

    Nam, I. F.; Zhuk, V. V.


    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  2. Accelerating Multiple Compound Comparison Using LINGO-Based Load-Balancing Strategies on Multi-GPUs

    Directory of Open Access Journals (Sweden)

    Chun-Yuan Lin


    Full Text Available Compound comparison is an important task for the computational chemistry. By the comparison results, potential inhibitors can be found and then used for the pharmacy experiments. The time complexity of a pairwise compound comparison is O(n2, where n is the maximal length of compounds. In general, the length of compounds is tens to hundreds, and the computation time is small. However, more and more compounds have been synthesized and extracted now, even more than tens of millions. Therefore, it still will be time-consuming when comparing with a large amount of compounds (seen as a multiple compound comparison problem, abbreviated to MCC. The intrinsic time complexity of MCC problem is O(k2n2 with k compounds of maximal length n. In this paper, we propose a GPU-based algorithm for MCC problem, called CUDA-MCC, on single- and multi-GPUs. Four LINGO-based load-balancing strategies are considered in CUDA-MCC in order to accelerate the computation speed among thread blocks on GPUs. CUDA-MCC was implemented by C+OpenMP+CUDA. CUDA-MCC achieved 45 times and 391 times faster than its CPU version on a single NVIDIA Tesla K20m GPU card and a dual-NVIDIA Tesla K20m GPU card, respectively, under the experimental results.

  3. Accelerating Multiple Compound Comparison Using LINGO-Based Load-Balancing Strategies on Multi-GPUs. (United States)

    Lin, Chun-Yuan; Wang, Chung-Hung; Hung, Che-Lun; Lin, Yu-Shiang


    Compound comparison is an important task for the computational chemistry. By the comparison results, potential inhibitors can be found and then used for the pharmacy experiments. The time complexity of a pairwise compound comparison is O(n (2)), where n is the maximal length of compounds. In general, the length of compounds is tens to hundreds, and the computation time is small. However, more and more compounds have been synthesized and extracted now, even more than tens of millions. Therefore, it still will be time-consuming when comparing with a large amount of compounds (seen as a multiple compound comparison problem, abbreviated to MCC). The intrinsic time complexity of MCC problem is O(k (2) n (2)) with k compounds of maximal length n. In this paper, we propose a GPU-based algorithm for MCC problem, called CUDA-MCC, on single- and multi-GPUs. Four LINGO-based load-balancing strategies are considered in CUDA-MCC in order to accelerate the computation speed among thread blocks on GPUs. CUDA-MCC was implemented by C+OpenMP+CUDA. CUDA-MCC achieved 45 times and 391 times faster than its CPU version on a single NVIDIA Tesla K20m GPU card and a dual-NVIDIA Tesla K20m GPU card, respectively, under the experimental results.

  4. A New Way in Deciding NOAEL Based on the Findings from GLP-Toxicity Test


    Park, Yeong-Chul; Cho, Myung-Haing


    The FDA guidance focuses on the use of the NOAEL to establish the maximum recommended starting dose. The majority of NOAEL has been described inaccurately or incompletely in final reports for 90-days repeated dose toxicity test based on GLP (good laboratory practice) regulation. This is the most serious one of reasons for why most pharmaceutical companies targeting global markets have disregarded the final report produced from GLP facilities in Korea. The problems in deciding NOAEL reflected ...

  5. Normalization references for USEtoxTM-based toxic impact categories: North American and European economic systems


    Laurent, Alexis; Lautier, Anne; Rosenbaum, Ralph K.; Olsen, Stig Irving; Hauschild, Michael Zwicky


    As an optional step of the life cycle impact assessment (LCIA) phase in the ISO standards, normalization aims to express the magnitude of the impacts by comparing the characterized results against a common reference situation - the normalization references. In this study, we used inventories of two economic regions, North America and Europe, to calculate normalization references for the three currently-modelled USEtoxTM-based impact categories, i.e. freshwater ecotoxicity, human toxicity, div...

  6. [Determination of purine compounds and purine bases in food]. (United States)

    Colling, M; Wolfram, G


    The total purine content and the content of RNA, DNA, nucleotides, nucleosides and free purine bases has been determined in commercial raw food. After hydrolysing food samples with acid, the total purine content is enzymatically determined as uric acid. For the determination of the nucleic acid content, a method is chosen that allows for the analysis of the composition of nucleic acids. The amount of purine bound in nucleic acids and of purine bound in nucleotides, nucleosides and free bases is very different. The content of nucleic acids is especially high in the innards of veal, pork and beef. In these samples the quantity of purine bound in nucleotides, nucleosides and bases is very small. In trout and herring, however, more purine is bound in RNA and DNA. The same is true of roe, pork and beef muscle. Peas and beans have the lowest total purine content of all the samples examined.

  7. Common toxicities and objective response rate in metastatic colorectal cancer patients treated with irinotecan based regimens

    Institute of Scientific and Technical Information of China (English)

    Liu Huang; Xin Liao; Qianqian Yu; Qiang Fu; Kai Qin; Huanlei Wu; Lihong Zhang; Xianglin Yuan


    Objective: The aim of our study was to investigate if common toxicities are correlated to objective response rate (ORR) in metastatic colorectal cancer (mCRC) patients treated by irinotecan based regimens. Methods: Univariate and multivariate logistic regression analyses were performed to evaluate correlations between common toxicities and binary ORR in 106 mCRC patients from a prospective cohort treated with irinotecan based regimens. Results: The most frequent severe toxicities (Grade 3/4) were as follows: neutropenia (27.4%), diarrhea (16.9%), leucopenia (12.6%), vomiting (3.2%) and thrombocytopenia (2.1%). Thrombocytosis was observed in 25 (26.3%) patients. ORR was 25.3%. Thrombocytopenia (P = 0.014), line of chemotherapy (P = 0.028) and thrombocytosis (P = 0.033) were correlated with ORR in univariate analysis. In multivariate analysis, thrombocytopenia (odds ratio [OR] = 8.600, 95% confidence interval [CI] = 1.705–43.385, P = 0.009) and first line chemotherapy (OR = 5.155, 95% CI = 1.153–23.256, P = 0.032) positively related to ORR. Conclusion: Throm-bocytopenia may be an indicator of ORR in mCRC patients treated by irinotecan plus 5-fluorouracil/capecitabine. Evidence is not strong enough to prove that irinotecan based regimens-induced diarrhea, leucopenia, neutropenia or vomiting is associ-ated with ORR.


    Energy Technology Data Exchange (ETDEWEB)

    Panagiotis G. Smirniotis; Robert G. Jenkins


    The work performed during this project focused on the identification of materials capable of providing high activity and selectivity for the selective catalytic reduction of nitric oxide with ammonia. The material surface characteristics were correlated with the catalytic behavior of our catalysts to increase our understanding and to help improve the DeNO{sub x} efficiency. The catalysts employed in this study include mixed oxide composite powders (TiO{sub 2}-Cr{sub 2}O{sub 3}, TiO{sub 2}-ZrO{sub 2}, TiO{sub 2}-WO{sub 3}, TiO{sub 2}-SiO{sub 2}, and TiO{sub 2}-Al{sub 2}O{sub 3}) loaded with varying amounts of V{sub 2}O{sub 5}, along with 5 different commercial sources of TiO{sub 2}. V{sub 2}O{sub 5} was added to the commercial sources of TiO{sub 2} to achieve monolayer coverage. Since the valence state of vanadium in the precursor solution during the impregnation step significantly impacted catalytic performance, catalysts were synthesized from both V{sup +4} and V{sup +5} solutions explain this phenomenon. Specifically, the synthesis of catalysts from V{sup 5+} precursor solutions yields lower-performance catalysts compared to the case of V{sup 4+} under identical conditions. Aging the vanadium precursor solution, which is associated with the reduction of V{sup 5+} to V{sup 4+} (VO{sub 2}{sup +} {yields} VO{sup 2+}), prior to impregnation results in catalysts with excellent catalytic behavior under identical activation and operating conditions. This work also added vanadia to TiO{sub 2}-based supports with low crystallinity. These supports, which have traditionally performed poorly, are now able to function as effective SCR catalysts. Increasing the acidity of the support by incorporating oxides such as WO{sub 3} and Al{sub 2}O{sub 3} significantly improves the SCR activity and nitrogen selectivity. It was also found that the supports should be synthesized with the simultaneous precipitation of the corresponding precursors. The mixed oxide catalysts possess

  9. MBE Growth and Characterization of Hg Based Compounds and Heterostructures (United States)


    The molecular beam epitaxy ( MBE ) growth of Mercury Cadmium Telluride (Hg(1-x)Cd(x)Te) alloys and type III HgTe/Hg(1-x)Cd(x)Te heterostructures has...been discussed, including similarities and differences between the (0 0 1) and (1 1 2)Beta orientations. Furthermore, the MBE growth of HgTe-based

  10. Mg-based compounds for hydrogen and energy storage

    NARCIS (Netherlands)

    Crivello, J. -C.; Denys, R. V.; Dornheim, M.; Felderhoff, M.; Grant, D. M.; Huot, J.; Jensen, T. R.; de Jongh, P.|info:eu-repo/dai/nl/186125372; Latroche, M.; Walker, G. S.; Webb, C. J.; Yartys, V. A.

    Magnesium-based alloys attract significant interest as cost-efficient hydrogen storage materials allowing the combination of high gravimetric storage capacity of hydrogen with fast rates of hydrogen uptake and release and pronounced destabilization of the metal–hydrogen bonding in comparison with

  11. 复方苯佐卡因凝胶的局部毒性研究%Studies on topical toxicity of Benzocaine compound gel

    Institute of Scientific and Technical Information of China (English)

    韦宝伟; 刘布鸣; 陈力力; 刘元; 姚树汉


    Objective To evaluate the topical irritation and sensitization of Benzocaine compound gel. Methods Irritation tests of rat oral mucosa, rabbit eyes, and skin hypersensitivity tests in guinea pigs were used, in accordance with the 'Guidance for Irritation, Sensitization and Hemolytic Tests for Chemicals' by the State Food and Drug Administration. Results By application of 3 g·kg-1 to rat oral mucosa, or 0.1 g to rabbit eyes, Benzocaine compound gel exhibited no irritation or other toxicity. No sensitization was found when 0.2 g of the gel was applied to the guinea pig skin. Conclusion Benzocaine compound gel is not irritative to oral mucosa, and does not cause skin allergy.%目的 评价复方苯佐卡因凝胶的局部刺激性和致敏性.方法 依照国家食品药品监督管理局《化学药物刺激性、过敏性和溶血性研究技术指导原则》(以下简称指导原则),采用大鼠口腔黏膜刺激性实验法、兔眼刺激性实验法以及豚鼠皮肤致敏实验法.结果 复方苯佐卡因凝胶给大鼠口腔正常黏膜连续涂药3次,相当于3 g·kg-1,均无刺激和毒性反应;一次性按每只0.1g给兔眼结膜涂药,亦未出现刺激性反应;给每只豚鼠皮肤0.2g致敏接触和激发接触,均无过敏反应发生.结论 复方苯佐卡因凝胶对口腔黏膜无刺激性,对皮肤也没有致敏性.

  12. Exploiting NanoLuc luciferase for smartphone-based bioluminescence cell biosensor for (anti)-inflammatory activity and toxicity. (United States)

    Cevenini, Luca; Calabretta, Maria Maddalena; Lopreside, Antonia; Tarantino, Giuseppe; Tassoni, Annalisa; Ferri, Maura; Roda, Aldo; Michelini, Elisa


    The availability of smartphones with high-performance digital image sensors and processing power has completely reshaped the landscape of point-of-need analysis. Thanks to the high maturity level of reporter gene technology and the availability of several bioluminescent proteins with improved features, we were able to develop a bioluminescence smartphone-based biosensing platform exploiting the highly sensitive NanoLuc luciferase as reporter. A 3D-printed smartphone-integrated cell biosensor based on genetically engineered Hek293T cells was developed. Quantitative assessment of (anti)-inflammatory activity and toxicity of liquid samples was performed with a simple and rapid add-and-measure procedure. White grape pomace extracts, known to contain several bioactive compounds, were analyzed, confirming the suitability of the smartphone biosensing platform for analysis of untreated complex biological matrices. Such approach could meet the needs of small medium enterprises lacking fully equipped laboratories for first-level safety tests and rapid screening of new bioactive products. Graphical abstract Smartphone-based bioluminescence cell biosensor.

  13. In Vitro and In Vivo toxicity profiling of ammonium-based deep eutectic solvents.

    Directory of Open Access Journals (Sweden)

    Maan Hayyan

    Full Text Available The cytotoxic potential of ammonium-based deep eutectic solvents (DESs with four hydrogen bond donors, namely glycerine (Gl, ethylene glycol (EG, triethylene glycol (TEG and urea (U were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes.

  14. Whole-cell based label-free capacitive biosensor for rapid nanosize-dependent toxicity detection. (United States)

    Qureshi, Anjum; Pandey, Ashish; Chouhan, Raghuraj S; Gurbuz, Yasar; Niazi, Javed H


    Despite intensive studies on examining the toxicity of nanomaterials (NMs), our current understanding on potential toxicity in relation to size and cellular responses has remained limited. In this work, we have developed a whole-cell based capacitive biosensor (WCB) to determine the biological toxicity of nanoparticles (NPs) using iron oxide (Fe3O4) NPs as models. This WCB chip comprised of an array of capacitor sensors made of gold interdigitated microelectrodes on which living Escherichia coli cells were immobilized. Cells-on-chip was then allowed to interact with different sizes of Fe3O4 NPs (5, 20 and 100 nm) and concentration-depended cellular-responses were measured in terms of change in dielectric properties (capacitance) as a function of applied AC frequency. The WCB response showed smaller-sized Fe3O4 NPs (5 nm) induced maximum change in surface capacitance because of their effective cellular interaction with E. coli cells-on-chip indicating that the cells suffered from severe cellular deformation, which was confirmed by scanning electron microscopic (SEM) examination. Further our results were validated through their cell viability and E. coli responses at the interface of cell-membrane and NPs as a proof-of-concept. WCB response showed a size-dependent shift in maximum response level from 2 µg/ml of 5 nm sized NPs to 4 µg/ml with NP-sizes greater than 20 nm. The developed WCB offered real-time, label-free and noninvasive detection of cellular responses against Fe3O4 NPs' toxicity with speed, simplicity and sensitivity that can be extended to toxicity screening of various other NPs. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Catalytic synthesis of α-amino chromone phosphonates and their antimicrobial, toxicity and potential HIV-1 RT inhibitors based on silico screening. (United States)

    Jaiyeola, Abosede Oluwabukola; Anand, K; Kasumbwe, K; Ramesh, M; Gengan, R M


    The α-amino phosphonates exhibit a wide range of biological properties which create demand for simple and efficient synthetic routes of new molecules. In this study synthesis of a new series of derivatives of α-amino chromone phosphonates (ACPs) was reported using RhBT catalyst. The RhBT was first prepared by simply mixing boron nitride in a solution of rhodium acetate, under inert atmosphere for a week followed by filtration (yield: 92%). The catalyst can be re-used for up to four times and showed minimal loss of activity. The ACPs was prepared in a one pot reaction containing chromone based aldehydes, aniline derivatives and diethyl phosphite. The structures of these compounds were characterized by IR, (1)H NMR, (13)C NMR, (31)P NMR and high resolution mass spectral analysis. The synthesized ACPs were evaluated for their antimicrobial activities against three bacteria B. cereus, M. luteus, E. coli and one fungus C. albicans. The ACPs displayed selective toxicity toward the brine shrimp (Artemia salina). Compounds 8j and 8m was found to be less toxic to the brine shrimp and may have more valuable biological application. Furthermore, molecular docking studies were conducted to predict the possible therapeutic potential of ACPs. The compounds (8i, 8j, 8k and 8m) were predicted as highly active HIV-1 reverse transcriptase inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Research on the Sparse Representation for Gearbox Compound Fault Features Using Wavelet Bases

    Directory of Open Access Journals (Sweden)

    Chunyan Luo


    Full Text Available The research on gearbox fault diagnosis has been gaining increasing attention in recent years, especially on single fault diagnosis. In engineering practices, there is always more than one fault in the gearbox, which is demonstrated as compound fault. Hence, it is equally important for gearbox compound fault diagnosis. Both bearing and gear faults in the gearbox tend to result in different kinds of transient impulse responses in the captured signal and thus it is necessary to propose a potential approach for compound fault diagnosis. Sparse representation is one of the effective methods for feature extraction from strong background noise. Therefore, sparse representation under wavelet bases for compound fault features extraction is developed in this paper. With the proposed method, the different transient features of both bearing and gear can be separated and extracted. Both the simulated study and the practical application in the gearbox with compound fault verify the effectiveness of the proposed method.

  17. Chemical reactivity of hypervalent silicon compounds: The local hard and soft acids and bases principle viewpoint

    Indian Academy of Sciences (India)

    Francisco Méndez; María De L Romero; José L Gazquez


    The silicon atom may increase its coordination number to values greater than four, to form pentacoordinated compounds. It has been observed experimentally that, in general, pentacoordinated compounds show greater reactivity than tetracoordinated compounds. In this work, density functional theory is used to calculate the global softness and the condensed softness of the silicon atom for SiHF4- and SiHF$^{1-}_{5-n}$. The values obtained show that the global and condensed softness are greater in the pentacoordinated compounds than in the tetracoordinated compounds, a result that explains the enhanced reactivity. If the results are analysed through a local version of the hard and soft acids and bases principle, it is possible to suggest that in nucleophilic substitution reactions, soft nucleophiles preferably react with SiHF$^{1-}_{5-n}$, and hard nucleophiles with SiHF4-.

  18. Structural alert/reactive metabolite concept as applied in medicinal chemistry to mitigate the risk of idiosyncratic drug toxicity: a perspective based on the critical examination of trends in the top 200 drugs marketed in the United States. (United States)

    Stepan, Antonia F; Walker, Daniel P; Bauman, Jonathan; Price, David A; Baillie, Thomas A; Kalgutkar, Amit S; Aleo, Michael D


    Because of a preconceived notion that eliminating reactive metabolite (RM) formation with new drug candidates could mitigate the risk of idiosyncratic drug toxicity, the potential for RM formation is routinely examined as part of lead optimization efforts in drug discovery. Likewise, avoidance of "structural alerts" is almost a norm in drug design. However, there is a growing concern that the perceived safety hazards associated with structural alerts and/or RM screening tools as standalone predictors of toxicity risks may be over exaggerated. In addition, the multifactorial nature of idiosyncratic toxicity is now well recognized based upon observations that mechanisms other than RM formation (e.g., mitochondrial toxicity and inhibition of bile salt export pump (BSEP)) also can account for certain target organ toxicities. Hence, fundamental questions arise such as: When is a molecule that contains a structural alert (RM positive or negative) a cause for concern? Could the molecule in its parent form exert toxicity? Can a low dose drug candidate truly mitigate metabolism-dependent and -independent idiosyncratic toxicity risks? In an effort to address these questions, we have retrospectively examined 68 drugs (recalled or associated with a black box warning due to idiosyncratic toxicity) and the top 200 drugs (prescription and sales) in the United States in 2009 for trends in physiochemical characteristics, daily doses, presence of structural alerts, evidence for RM formation as well as toxicity mechanism(s) potentially mediated by parent drugs. Collectively, our analysis revealed that a significant proportion (∼78-86%) of drugs associated with toxicity contained structural alerts and evidence indicating that RM formation as a causative factor for toxicity has been presented in 62-69% of these molecules. In several cases, mitochondrial toxicity and BSEP inhibition mediated by parent drugs were also noted as potential causative factors. Most drugs were administered

  19. Rule-based Approach on Extraction of Malay Compound Nouns in Standard Malay Document (United States)

    Abu Bakar, Zamri; Kamal Ismail, Normaly; Rawi, Mohd Izani Mohamed


    Malay compound noun is defined as a form of words that exists when two or more words are combined into a single syntax and it gives a specific meaning. Compound noun acts as one unit and it is spelled separately unless an established compound noun is written closely from two words. The basic characteristics of compound noun can be seen in the Malay sentences which are the frequency of that word in the text itself. Thus, this extraction of compound nouns is significant for the following research which is text summarization, grammar checker, sentiments analysis, machine translation and word categorization. There are many research efforts that have been proposed in extracting Malay compound noun using linguistic approaches. Most of the existing methods were done on the extraction of bi-gram noun+noun compound. However, the result still produces some problems as to give a better result. This paper explores a linguistic method for extracting compound Noun from stand Malay corpus. A standard dataset are used to provide a common platform for evaluating research on the recognition of compound Nouns in Malay sentences. Therefore, an improvement for the effectiveness of the compound noun extraction is needed because the result can be compromised. Thus, this study proposed a modification of linguistic approach in order to enhance the extraction of compound nouns processing. Several pre-processing steps are involved including normalization, tokenization and tagging. The first step that uses the linguistic approach in this study is Part-of-Speech (POS) tagging. Finally, we describe several rules-based and modify the rules to get the most relevant relation between the first word and the second word in order to assist us in solving of the problems. The effectiveness of the relations used in our study can be measured using recall, precision and F1-score techniques. The comparison of the baseline values is very essential because it can provide whether there has been an improvement

  20. Food processing strategies to enhance phenolic compounds bioaccessibility and bioavailability in plant-based foods. (United States)

    Ribas-Agustí, Albert; Martín-Belloso, Olga; Soliva-Fortuny, Robert; Elez-Martínez, Pedro


    Phenolic compounds are important constituents of plant-based foods, as their presence is related to protective effects on health. To exert their biological activity, phenolic compounds must be released from the matrix during digestion in an absorbable form (bioaccessible) and finally absorbed and transferred to the bloodstream (bioavailable). Chemical structure and matrix interactions are some food-related factors that hamper phenolic compounds bioaccessibility and bioavailability, and that can be counteracted by food processing. It has been shown that food processing can induce chemical or physical modifications in food that enhance phenolic compounds bioaccessibility and bioavailability. These changes include: (i) chemical modifications into more bioaccessible and bioavailable forms; (ii) cleavage of covalent or hydrogen bonds or hydrophobic forces that attach phenolic compounds to matrix macromolecules; (iii) damaging microstructural barriers such as cell walls that impede the release from the matrix; and (iv) create microstructures that protect phenolic compounds until they are absorbed. Indeed, food processing can produce degradation of phenolic compounds, however, it is possible to counteract it by modulating the operating conditions in favor of increased bioaccessibility and bioavailability. This review compiles the current knowledge on the effects of processing on phenolic compounds bioaccessibility or bioavailability, while suggesting new guidelines in the search of optimal processing conditions as a step forward towards the design of healthier foods.

  1. In silico prediction of toxicity of non-congeneric industrial chemicals using ensemble learning based modeling approaches

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kunwar P., E-mail:; Gupta, Shikha


    Ensemble learning approach based decision treeboost (DTB) and decision tree forest (DTF) models are introduced in order to establish quantitative structure–toxicity relationship (QSTR) for the prediction of toxicity of 1450 diverse chemicals. Eight non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals was evaluated using Tanimoto similarity index. Stochastic gradient boosting and bagging algorithms supplemented DTB and DTF models were constructed for classification and function optimization problems using the toxicity end-point in T. pyriformis. Special attention was drawn to prediction ability and robustness of the models, investigated both in external and 10-fold cross validation processes. In complete data, optimal DTB and DTF models rendered accuracies of 98.90%, 98.83% in two-category and 98.14%, 98.14% in four-category toxicity classifications. Both the models further yielded classification accuracies of 100% in external toxicity data of T. pyriformis. The constructed regression models (DTB and DTF) using five descriptors yielded correlation coefficients (R{sup 2}) of 0.945, 0.944 between the measured and predicted toxicities with mean squared errors (MSEs) of 0.059, and 0.064 in complete T. pyriformis data. The T. pyriformis regression models (DTB and DTF) applied to the external toxicity data sets yielded R{sup 2} and MSE values of 0.637, 0.655; 0.534, 0.507 (marine bacteria) and 0.741, 0.691; 0.155, 0.173 (algae). The results suggest for wide applicability of the inter-species models in predicting toxicity of new chemicals for regulatory purposes. These approaches provide useful strategy and robust tools in the screening of ecotoxicological risk or environmental hazard potential of chemicals. - Graphical abstract: Importance of input variables in DTB and DTF classification models for (a) two-category, and (b) four-category toxicity intervals in T. pyriformis data. Generalization and predictive abilities of the

  2. Toxicity testing and chemical analyses of recycled fibre-based paper for food contact

    DEFF Research Database (Denmark)

    Binderup, Mona-Lise; Pedersen, Gitte Alsing; Vinggaard, Anne


    Food-contact materials, including paper, have to comply with a basic set of criteria concerning safety. This means that paper for food contact should not give rise to migration of components, which can endanger human health. The objectives of this pilot study were, first, to compare paper...... of different qualities as food-contact materials and to Perform a preliminary evaluation of their suitability from a safety point of view, and, second, to evaluate the use of different in vitro toxicity tests for screening of paper and board. Paper produced from three different categories of recycled fibres (B......-D) and a raw material produced from virgin fibres (A) were obtained from industry, and extracts were examined by chemical analyses and diverse in vitro toxicity test systems. The products tested were either based on different raw materials or different treatments were applied. Paper category B was made from 40...

  3. Biodegradability of ethylenediamine-based complexing agents and related compounds. (United States)

    Pitter, P; Sýkora, V


    The biological degradability (Zahn-Wellens test) of ethylenediamine derivatives with carboxymethyl and 2-hydroxyethyl groups was investigated. Mixed bacterial culture (activated sludge) was used as inoculum (non-adapted sludge and sludge adapted at different mean biomass retention time, the so-called sludge age). Biodegradability of ethylene(propylene)di(tri)amine-based complexing agents depends on the character and number of substituents and nitrogen atoms in the molecule. Tetra(penta)substituted derivatives with two or more tertiary nitrogen atoms and carboxymethyl or 2-hydroxyethyl groups in the molecule (EDTA, DTPA, PDTA, HEDTA) are very stable from an environmental point of view. On the contrary, disubstituted derivatives with two secondary nitrogen atoms in the molecule (e.g., EDDA) are potentially degradable.

  4. Fast preparation and thermal transport property of TiCoSb-based half-Heusler compounds

    Institute of Scientific and Technical Information of China (English)

    Xie Wen-Jie; Tang Xin-Feng; Zhang Qing-Jie


    TiCoSb-based half-Heusler compounds with the substitution of Zr for Ti have been prepared quickly by combining high-energy ball milling method with spark plasma sintering technique, and their thermal transport properties have been investigated. With the increase of the concentration of Zr, the thermal conductivity of Ti1-xZrxCoSb compounds decreases significantly. Compared with the thermal conductivity of TiCoSb compound, that of Ti0.5Zr0.5CoSb decreases by 200% at 1000 K.

  5. Influence of lead Inorganic Compounds on Combustion Rate of Double Base Rocket Propellants

    Directory of Open Access Journals (Sweden)

    V. B. Pillai


    Full Text Available The influence of lead nitrate, red lead, lead chromate, lead floride and lead carbonate on the combustion behaviour of double base propellants in the pressure range-35-140kg/cm /sup 2/ was studied. While all these compounds increased burning rates in lower pressure range (35-60 kg/cm/sup 2/ and higher pressure range (120-140 kg/cm/sup 2/, only lead chromate and lead fluoride were effective in the intermediate pressure range of 60-105 kg/cm/sup 2/. None of these compounds were effective as platonizer, except lead fluoride, which lowered n value to 0.34 in the lower pressure range. Addition of carbon black along with lead compounds raised burning rates further and reduced n values significantly in the higher pressure regins. A probable mechanism on the role of lead compounds studied has been suggested based on burning rate and DTA results.

  6. Diversity selection of compounds based on 'protein affinity fingerprints' improves sampling of bioactive chemical space. (United States)

    Nguyen, Ha P; Koutsoukas, Alexios; Mohd Fauzi, Fazlin; Drakakis, Georgios; Maciejewski, Mateusz; Glen, Robert C; Bender, Andreas


    Diversity selection is a frequently applied strategy for assembling high-throughput screening libraries, making the assumption that a diverse compound set increases chances of finding bioactive molecules. Based on previous work on experimental 'affinity fingerprints', in this study, a novel diversity selection method is benchmarked that utilizes predicted bioactivity profiles as descriptors. Compounds were selected based on their predicted activity against half of the targets (training set), and diversity was assessed based on coverage of the remaining (test set) targets. Simultaneously, fingerprint-based diversity selection was performed. An original version of the method exhibited on average 5% and an improved version on average 10% increase in target space coverage compared with the fingerprint-based methods. As a typical case, bioactivity-based selection of 231 compounds (2%) from a particular data set ('Cutoff-40') resulted in 47.0% and 50.1% coverage, while fingerprint-based selection only achieved 38.4% target coverage for the same subset size. In conclusion, the novel bioactivity-based selection method outperformed the fingerprint-based method in sampling bioactive chemical space on the data sets considered. The structures retrieved were structurally more acceptable to medicinal chemists while at the same time being more lipophilic, hence bioactivity-based diversity selection of compounds would best be combined with physicochemical property filters in practice.

  7. Exploring Sustainable Rocket Fuels: [Imidazolyl-Amine-BH2](+)-Cation-Based Ionic Liquids as Replacements for Toxic Hydrazine Derivatives. (United States)

    Huang, Shi; Qi, Xiujuan; Zhang, Wenquan; Liu, Tianlin; Zhang, Qinghua


    The application of hypergolic ionic liquids as propellant fuels is a newly emerging area in the fields of chemistry and propulsion science. Herein, a new class of [imidazolyl-amine-BH2](+)-cation-based ionic liquids, which included fuel-rich anions, such as dicyanamide (N(CN)2(-)) and cyanoborohydride (BH3CN(-)) anions, were synthesized and characterized. As expected, all of the ionic liquids exhibited spontaneous combustion upon contact with the oxidizer 100 % HNO3. The densities of these ionic liquids varied from 0.99-1.12 g cm(-3), and the heats of formation, predicted based on Gaussian 09 calculations, were between -707.7 and 241.8 kJ mol(-1). Among them, the salt of compound 5, that is, (1-allyl-1H-imidazole-3-yl)-(trimethylamine)-dihydroboronium dicyanamide, exhibited the lowest viscosity (168 MPa s), good thermal properties (Tg 130 °C), and the shortest ignition-delay time (18 ms) with 100 % HNO3. These ionic fuels, as "green" replacements for toxic hydrazine-derivatives, may have potential applications as bipropellant formulations.

  8. Crystal structure prediction and electronic properties of Li-based ternary compounds

    Energy Technology Data Exchange (ETDEWEB)

    Vergniory, Maia G.; Sanna, Antonio; Ernst, Arthur; Romero, Aldo H.; Gross, Eberhard K.U. [Max Planck Institute of Microstructure Physics, 06120 Halle (Germany); Marques, Miguel A.L.; Botti, Silvana; Valencia, Irais [Universite de Lyon, F-69000 Lyon, France and LPMCN, CNRS, UMR 5586, Universite Lyon 1, F-69622 Villeurbanne (France); Amsler, Max; Goedecker, Stefan [Department of Physics, Universitaet Basel, Klingelbergstr. 82, 4056 Basel (Switzerland); Chulkov, Evgueni V. [Donostia International Physics Center, 20018 Donostia-San Sebastian (Spain)


    On the basis of ab initio first principles and using the Minimal Hopping Algorithm we predict the crystal structure of non synthesized LiYZ (Y=Au,Ag, Z=Te,Se) based ternary compounds. We find that, as distinct from expectation, the crystal structure depends strongly on the composition, thus every compound belongs to a different symmetry group and has complexly different electronic properties. We analyze the fundamental physics below these features considering the calculated ground state structure.

  9. Synthesis and Antimicrobial Activity of New Schiff Base Compounds Containing 2-Hydroxy-4-pentadecylbenzaldehyde Moiety

    Directory of Open Access Journals (Sweden)

    Gadada Naganagowda


    Full Text Available Various novel Schiff base compounds have been synthesized by reaction of 2-hydroxy-4-pentadecylbenzaldehyde with substituted benzothiophene-2-carboxylic acid hydrazide and different substituted aromatic or heterocyclic amines in the presence of acetic acid in ethanol. The structures of all these compounds were confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR, and mass spectral data and have been screened for antibacterial and antifungal activity.

  10. Clinical studies with oral lipid based formulations of poorly soluble compounds

    DEFF Research Database (Denmark)

    Fatouros, Dimitrios; Karpf, Ditte M; Nielsen, Flemming S


    of these properties on the in vivo performance of the formulation. Equally important is the effect of concurrent food intake on the bioavailability of poorly soluble compounds. The effect of food on the bioavailability of compounds formulated in lipid and surfactant based formulations is also reviewed.......This work is an attempt to give an overview of the clinical data available on lipid based formulations. Lipid and surfactant based formulations are recognized as a feasible approach to improve bioavailability of poorly soluble compounds. However not many clinical studies have been published so far....... Several drug products intended for oral administration have been marketed utilizing lipid and surfactant based formulations. Sandimmune((R)) and Sandimmune Neoral((R)) (cyclosporin A, Novartis), Norvir((R)) (ritonavir), and Fortovase((R)) (saquinavir) have been formulated in self-emulsifying drug delivery...

  11. Evaluation of the toxic effects of brominated compounds (BDE-47, 99, 209, TBBPA) and bisphenol A (BPA) using a zebrafish liver cell line, ZFL

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jie; Chan, King Ming, E-mail:


    Highlights: • A homologous zebrafish thyroid hormone (TH) receptor (TR) reporter gene system was developed in a zebrafish liver cell-line (ZFL) to study the possible effects of chemicals on TR activities. • BPA was found to have antagonistic effects on T3 induced TR activity, BDE-47, BDE-99, and TBBPA did not show any interference of TR activity. • Down regulation of deiodinases and some sulfation enzymes or phase II enzymes by the tested chemicals indicated their impacts on TH eleiminations. • The up-regulation of tranthyretin by BDE-47 at 96 h long-term exposure gave a link to the CYP family for its role in producing a more toxic and oxidized form. - Abstract: The toxic effects of three polybrominated diphenyl ether (PBDE) congeners (BDE-47, -99, and -209), tetrabromobisphenol A (TBBPA) and bisphenol A (BPA), were evaluated by determining their 24 h and 96 h median lethal concentrations using a zebrafish liver cell line, ZFL. It was found that BDE-47, BDE-99 and TBBPA showed comparative cytotoxicity within the range of 1.2–4.2 μM, and were more toxic than BPA (367.1 μM at 24 h and 357.6 μM at 96 h). However, BDE-209 induced only 15% lethality with exposures up to 25 μM. The molecular stresses of BDE-47, -99, TBBPA and BPA involved in thyroid hormone (TH) homeostasis and hepatic metabolism were also investigated. Using a reporter gene system to detect zebrafish thyroid hormone receptor β (zfTRβ) transcriptional activity, the median effective concentration of triiodothyronine (T3) was determined to be 9.2 × 10{sup −11} M. BDE-47, BDE-99, TBBPA and BPA alone, however, did not exhibit zfTRβ agonistic activity. BPA displayed T3 (0.1 nM) induced zfTRβ antagonistic activity with a median inhibitory concentration of 19.3 μM. BDE-47, BDE-99 and TBBPA displayed no antagonistic effects of T3-induced zfTRβ activity. Target gene expressions were also examined under acute exposures. The significant inhibition of different types of deiodinases by all of

  12. Hydrogen trapping properties of Zr-based intermetallic compounds in the presence of CO contaminant gas

    Energy Technology Data Exchange (ETDEWEB)

    Prigent, Jocelyn [Chimie Metallurgie des Terres Rares, ICMPE-UMR 7182, CNRS, 2-8 rue Henri Dunant, 94320 Thiais (France); Latroche, Michel, E-mail: [Chimie Metallurgie des Terres Rares, ICMPE-UMR 7182, CNRS, 2-8 rue Henri Dunant, 94320 Thiais (France); Leoni, Elisa; Rohr, Valentin [AREVA NC, 1, rue des Herons, 78182 Montigny Le Bretonneux (France)


    Research highlights: > Hydrogen absorption in the presence of carbon monoxide is reported for several Zr rich intermetallic compounds. > Absorption rates have been determined and compared for pure and CO-containing hydrogen gases. > Using intermetallic compounds as getter materials in the presence of contaminant gases has been demonstrated. - Abstract: Intermetallic compounds, as hydrogen getters, are considered to control the quantity of hydrogen generated in radioactive waste packaging. The compounds ZrCo, Zr{sub 2}Fe and a Zr-rich Zr-Ti-V alloy have been chosen as they form very stable hydrides at ambient temperature. However, other gases are produced in the packaging such as carbon monoxide, a gas known to poison the surface of intermetallic compounds and to hinder the hydrogen sorption reaction. The three Zr-based compounds have been first characterized regarding their metallurgical state and their gas sorption properties toward pure hydrogen. Then, the sorption properties of the activated materials have been studied using a mixture of 5 vol.% CO + 95 vol.% H{sub 2}. We demonstrated that though the presence of CO sharply slows down the reaction rate the activated compounds still show significant sorption properties. Therefore, the presence of contaminant gases is not detrimental for the target application.


    Directory of Open Access Journals (Sweden)

    Bambang Kuswandi


    Full Text Available An electrochemical method for the detection of the genotoxic compounds using a DNA-modified electrode was developed. This electrode was successfully used for the electrochemical detection of genotoxic compounds in water samples. The electrochemical results clearly demonstrated that, the development is related to the molecular interaction between the surface-linked DNA obtained from calf thymus and the target compounds, such as pollutants, in order to develop a simple device for rapid screening of genotoxic compounds in environmental samples. The detection of such compounds was measured by their effect on the oxidation signal of the guanine peak of the DNA immobilised on the surface of carbon based Screen-Printed Electrode (SPE in disposable mode, and monitored by square-wave voltametric analysis. The DNA biosensor is able to detect known intercalating and groove-binding genotoxic compounds such as Dioxin, Bisphenol A, PCBs, and Phtalates. Application to real water samples is discussed and reported.   Keywords: electrochemical, screen-printed electrode, DNA biosensor, genotoxic compounds

  14. A fluorescence-based hydrolytic enzyme activity assay for quantifying toxic effects of Roundup® to Daphnia magna

    DEFF Research Database (Denmark)

    Ørsted, Michael; Roslev, Peter


    Daphnia magna is a widely used model organism for aquatic toxicity testing. In the present study, we investigated the hydrolytic enzyme activity of D. magna after exposure to toxicant stress. In vivo enzyme activity was quantified using 15 fluorogenic enzyme probes based on 4-methylumbelliferyl o...... that the fluorescence based hydrolytic enzyme activity assay (FLEA assay) can be used as an index of D. magna stress. Combining enzyme activity with fluorescence measurements may be applied as a simple and quantitative supplement for toxicity testing with D. magna....

  15. Synthesis, Structure and Properties of Melamine-Based pTHF-Urethane Supramolecular Compounds

    NARCIS (Netherlands)

    Öjelund, Karin; Loontjens, Ton; Steeman, Paul; Palmans, Anja; Maurer, Frans


    The properties of melamine based supramolecular compounds have been studied with rheological, thermal, mechanical, dielectric and scattering techniques and compared with similar covalently bonded materials. The complexes are based on a linear pTHF-diol (M¯n=1 000) connected via a diisocyanate with m

  16. Temporal Lobe Toxicity Analysis After Proton Radiation Therapy for Skull Base Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pehlivan, Berrin [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Ares, Carmen, E-mail: [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Lomax, Antony J.; Stadelmann, Otto; Goitein, Gudrun; Timmermann, Beate; Schneider, Ralf A.; Hug, Eugen B. [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland)


    Purpose: Temporal lobe (TL) parenchyma toxicity constitutes one of the most frequent late adverse event in high-dose proton therapy (PT) for tumors of the skull base. We analyzed clinical events with dosimetric parameters in our patients treated for skull base tumors with spot-scanning PT. Methods and Materials: Between 1998 and 2005, a total of 62 patients received PT to a median dose of 71.7 Gy (relative biologic effectiveness [RBE]) (range, 63-74 Gy). The dose-volume histogram of each TL and the entire brain parenchyma (BP) were analyzed according to maximum, mean, and minimum dose as well as doses to 0.5, 1, 2, and 3 cc of brain volume (D{sub 0.5}, D{sub 1}, D{sub 2}, D{sub 3}) and correlated with clinical events. Generalized equivalent uniform dose (gEUD) values were calculated. Results: At a mean follow-up of 38 months (range, 14-92 months), 2 patients had developed symptomatic Grade 3 and 5 patients asymptomatic Grade 1 TL toxicity. Mean doses to a 2-cc volume of BP increased from 71 {+-} 5 Gy (RBE) for no toxicity to 74 {+-} 5 Gy (RBE) for Grade 1 and to 76 {+-} 2 Gy (RBE) for Grade 3 toxicity. TL events occurred in 6 of 7 patients (86%) at or above dose levels of {>=}64 Gy (RBE) D{sub 3}, {>=}68 Gy (RBE) D{sub 2}, {>=}72 Gy (RBE) D{sub 1}, and {>=}73 Gy (RBE) D{sub 0.5}, respectively (p = NS). No statistically significant dose/volume threshold was detected between patients experiencing no toxicity vs. Grade 1 or Grade 3. A strong trend for Grade 1 and 3 events was observed, when the gEUD was 60 Gy. Conclusions: A statistically significant normal tissue threshold dose for BP has not been successfully defined. However, our data suggest that tolerance of TL and BP to fractionated radiotherapy appears to be correlated with tissue volume included in high-dose regions. Additional follow-up time and patient accrual is likely needed to achieve clinical significance for these dose-volume parameters investigated. Our findings support the importance of establishing

  17. Target identification of natural products and bioactive compounds using affinity-based probes. (United States)

    Pan, Sijun; Zhang, Hailong; Wang, Chenyu; Yao, Samantha C L; Yao, Shao Q


    Covering: 2010 to 2014.Advances in isolation, synthesis and screening strategies have made many bioactive substances available. However, in most cases their putative biological targets remain unknown. Herein, we highlight recent advances in target identification of natural products and bioactive compounds by using affinity-based probes. Aided by photoaffinity labelling, this strategy can capture potential cellular targets (on and off) of a natural product or bioactive compound in live cells directly, even when the compound-target interaction is reversible with moderate affinity. The knowledge of these targets may help uncover molecular pathways and new therapeutics for currently untreatable diseases. In this highlight, we will introduce the development of various photoactivatable groups, their synthesis and applications in target identification of natural products and bioactive compounds, with a focus on work done in recent years and from our laboratory. We will further discuss the strengths and weaknesses of each group and the outlooks for this novel proteome-wide profiling strategy.

  18. Mechanism of ultrasonic-pulse electrochemical compound machining based on particles

    Institute of Scientific and Technical Information of China (English)

    张成光; 张勇; 张飞虎


    The electric double layer with the transmission of particles was presented based on the principle of electrochemistry. In accordance with this theory, the cavitation catalysis removal mechanism of ultrasonic-pulse electrochemical compound machining (UPECM) based on particles was proposed. The removal mechanism was a particular focus and was thus validated by experiments. The principles and experiments of UPECM were introduced, and the removal model of the UPECM based on the principles of UPECM was established. Furthermore, the effects of the material removal rate for the main processing parameters, including the particles size, the ultrasonic vibration amplitude, the pulse voltage and the minimum machining gap between the tool and the workpiece, were also studied through UPECM. The results show that the particles promote ultrasonic-pulse electrochemical compound machining and thus act as the catalyzer of UPECM. The results also indicate that the processing speed, machining accuracy and surface quality can be improved under UPECM compound machining.

  19. Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing. (United States)

    Hu, Li-Xin; Ying, Guang-Guo; Chen, Xiao-Wen; Huang, Guo-Yong; Liu, You-Sheng; Jiang, Yu-Xia; Pan, Chang-Gui; Tian, Fei; Martin, Francis L


    Traditional duckweed toxicity tests only measure plant growth inhibition as an endpoint, with limited effects-based data. The present study aimed to investigate whether Fourier-transform infrared (FTIR) spectroscopy could enhance the duckweed (Lemna minor L.) toxicity test. Four chemicals (Cu, Cd, atrazine, and acetochlor) and 4 metal-containing industrial wastewater samples were tested. After exposure of duckweed to the chemicals, standard toxicity endpoints (frond number and chlorophyll content) were determined; the fronds were also interrogated using FTIR spectroscopy under optimized test conditions. Biochemical alterations associated with each treatment were assessed and further analyzed by multivariate analysis. The results showed that comparable x% of effective concentration (ECx) values could be achieved based on FTIR spectroscopy in comparison with those based on traditional toxicity endpoints. Biochemical alterations associated with different doses of toxicant were mainly attributed to lipid, protein, nucleic acid, and carbohydrate structural changes, which helped to explain toxic mechanisms. With the help of multivariate analysis, separation of clusters related to different exposure doses could be achieved. The present study is the first to show successful application of FTIR spectroscopy in standard duckweed toxicity tests with biochemical alterations as new endpoints. Environ Toxicol Chem 2017;36:346-353. © 2016 SETAC.

  20. Diffusion dynamics and concentration of toxic materials from quantum dots-based nanotechnologies: an agent-based modeling simulation framework

    Energy Technology Data Exchange (ETDEWEB)

    Agusdinata, Datu Buyung, E-mail:; Amouie, Mahbod [Northern Illinois University, Department of Industrial & Systems Engineering and Environment, Sustainability, & Energy Institute (United States); Xu, Tao [Northern Illinois University, Department of Chemistry and Biochemistry (United States)


    Due to their favorable electrical and optical properties, quantum dots (QDs) nanostructures have found numerous applications including nanomedicine and photovoltaic cells. However, increased future production, use, and disposal of engineered QD products also raise concerns about their potential environmental impacts. The objective of this work is to establish a modeling framework for predicting the diffusion dynamics and concentration of toxic materials released from Trioctylphosphine oxide-capped CdSe. To this end, an agent-based model simulation with reaction kinetics and Brownian motion dynamics was developed. Reaction kinetics is used to model the stability of surface capping agent particularly due to oxidation process. The diffusion of toxic Cd{sup 2+} ions in aquatic environment was simulated using an adapted Brownian motion algorithm. A calibrated parameter to reflect sensitivity to reaction rate is proposed. The model output demonstrates the stochastic spatial distribution of toxic Cd{sup 2+} ions under different values of proxy environmental factor parameters. With the only chemistry considered was oxidation, the simulation was able to replicate Cd{sup 2+} ion release from Thiol-capped QDs in aerated water. The agent-based method is the first to be developed in the QDs application domain. It adds both simplicity of the solubility and rate of release of Cd{sup 2+} ions and complexity of tracking of individual atoms of Cd at the same time.

  1. A lab-on-chip cell-based biosensor for label-free sensing of water toxicants. (United States)

    Liu, F; Nordin, A N; Li, F; Voiculescu, I


    This paper presents a lab-on-chip biosensor containing an enclosed fluidic cell culturing well seeded with live cells for rapid screening of toxicants in drinking water. The sensor is based on the innovative placement of the working electrode for the electrical cell-substrate impedance sensing (ECIS) technique as the top electrode of a quartz crystal microbalance (QCM) resonator. Cell damage induced by toxic water will cause a decrease in impedance, as well as an increase in the resonant frequency. For water toxicity tests, the biosensor's unique capabilities of performing two complementary measurements simultaneously (impedance and mass-sensing) will increase the accuracy of detection while decreasing the false-positive rate. Bovine aortic endothelial cells (BAECs) were used as toxicity sensing cells. The effects of the toxicants, ammonia, nicotine and aldicarb, on cells were monitored with both the QCM and the ECIS technique. The lab-on-chip was demonstrated to be sensitive to low concentrations of toxicants. The responses of BAECs to toxic samples occurred during the initial 5 to 20 minutes depending on the type of chemical and concentrations. Testing the multiparameter biosensor with aldicarb also demonstrated the hypothesis that using two different sensors to monitor the same cell monolayer provides cross validation and increases the accuracy of detection. For low concentrations of aldicarb, the variations in impedance measurements are insignificant in comparison with the shifts of resonant frequency monitored using the QCM resonator. A highly linear correlation between signal shifts and chemical concentrations was demonstrated for each toxicant.

  2. Leaching of the potentially toxic pollutants from composites based on waste raw material

    Directory of Open Access Journals (Sweden)

    Terzić Anja


    Full Text Available The disposal of the fly ash generated in coal based power-plants may pose a significant risk to the environment due to the possible leaching of hazardous pollutants, such as toxic metals. Also, there is a risk of leaching even when fly ash is built-in the construction composites. Fly ashes from various landfills were applied in several composite samples (mortar, concrete and brick without any physical or thermal pre-treatment. The leachability of the potentially toxic pollutants from the fly ash based products was investigated. The leaching behavior and potential environmental impact of the 11 potentially hazardous elements was tracked: Pb, Cd, Zn, Cu, Ni, Cr, Hg, As, Ba, Sb and Se. A detailed study of physico-chemical characteristics of the fly ash, with accent on trace elements and the chemical composition investigation is included. Physico/chemical properties of fly ash were investigated by means of X-ray fluorescence, differential thermal analysis and X-ray diffraction methods. Scanning electron microscope was used in microstructural analysis. The results show that most of the elements are more easily leachable from the fly ash in comparison with the fly ash based composites. The leaching of investigated pollutants is within allowed range thus investigated fly ashes can be reused in construction materials production.

  3. Characterization of the MSMEG_2631 Gene (mmp) Encoding a Multidrug and Toxic Compound Extrusion (MATE) Family Protein in Mycobacterium smegmatis and Exploration of Its Polyspecific Nature Using Biolog Phenotype MicroArray


    Mishra, Mukti Nath; Daniels, Lacy


    In Mycobacterium, multidrug efflux pumps can be associated with intrinsic drug resistance. Comparison of putative mycobacterial transport genes revealed a single annotated open reading frame (ORF) for a multidrug and toxic compound extrusion (MATE) family efflux pump in all sequenced mycobacteria except Mycobacterium leprae. Since MATE efflux pumps function as multidrug efflux pumps by conferring resistance to structurally diverse antibiotics and DNA-damaging chemicals, we studied this gene (...

  4. Toxicity of 56 substances to trees. (United States)

    Clausen, Lauge Peter Westergaard; Trapp, Stefan


    Toxicity data of substances to higher plants is needed for the purpose of risk assessment, site evaluation, phytoremediation, and plant protection. However, the results from the most common phytotoxicity tests, like the OECD algae and Lemna test, are not necessarily valid for higher terrestrial plants. The willow tree toxicity test uses inhibition of transpiration (aside of growth and water use efficiency) of willow cuttings grown in spiked solutions or soils as end point to quantify toxicity. This overview presents results from 60 studies including 24 new unpublished experiments for 56 different chemicals or substrates. Highest toxicity (EC50 algae, while volatile compounds like chlorinated solvents or benzene, toluene, ethylbenzene, and xylene had less effect on trees than on these aquatic plants, due to volatilization from leaves and test media. In particular low (g/L range) toxicity was observed for tested nanomaterials. Effects of pharmaceuticals (typically weak acids or bases) depended strongly of the solution pH. Like for algae, baseline toxicity was observed for willows, which is related to the water solubility of the compounds, with absolute chemical activity ranging from 0.01 to 0.1, but with several exceptions. We conclude that the willow tree toxicity test is a robust method for relating uptake, accumulation, and metabolism of substances to the toxicity to trees.

  5. Toxicity assessment of organochlorine compounds detected in water environment using cultured human cell lines; Hito yurai saibo baiyokei wo mochiita suikankyo shiryochu no yuki enso kagobutsu no dokusei hyoka

    Energy Technology Data Exchange (ETDEWEB)

    Kunimoto, M.; Yonemoto, J.; Soma, Y.; Nakasugi, O. [National Institute for Environmental Studies, Tsukuba (Japan)


    As part of validation processes of in vitro toxicity assays for the risk assessment of environmental hazards, we applied an in vitro toxicity test using two human cell lines, neuroblastoma NB-1 cells and glioblastoma U-87 MG cells, to the assessment of organochlorine compounds detected in the water environment. The in vitro toxicity assay using NB-1 cells was calibrated by testing reference chemicals proposed by MEIC (Multicenter Evaluation of In Vitro Cytotoxicity), an international program for the validation of in vitro cytotoxicity assays. Beforehand, an assay using cells in frozen stock without subcultivation was examined by comparing IC50 values with the ordinary assay using subcultured cells. IC50 values for MEIC reference chemicals from the former assay showed good correlation with those from the latter assay, suggesting that the assay using cells in frozen stock can be used at least for the assessment of basal cytotoxicity. IC50 values for ten organochlorine compounds frequently detected in the sediment samples from contaminated rivers, p-chloroaniline, 3,4-dichloroaniline, p-dichlorobenzene, o-dichlorobenzene, Tris (2-chloroethyl)-phosphate, 2,5-dichlorophenol, 2,5-dichloroanisol, Triclosan and Triclocarban, were obtained with the in vitro assays and compared with their LD50 values in rats. No significant correlation, however, was seen between the IC50 and LD50 values, indicating that further improvement of in vitro toxicity assays is necessary for the application to the risk assessment of environmental hazards. 7 refs., 4 figs., 1 tab.

  6. Theoretical investigation on thermoelectric properties of Cu-based chalcopyrite compounds (United States)

    Wang, Biao; Xiang, Hongjun; Nakayama, Tsuneyoshi; Zhou, Jun; Li, Baowen


    Cu-based materials are potential candidates for commercial thermoelectric materials due to their abundance, nontoxicity, and high performance. We incorporate the multiband Boltzmann transport equations with first-principles calculations to theoretically investigate the thermoelectric properties of Cu-based chalcopyrite compounds. As a demonstration of our method, the thermoelectric properties of quaternary compounds Cu2ZnSnX4 (X = S, Se) and ternary compounds CuBTe2 (B = Ga, In) are studied. We systematically calculate the electrical conductivity, the Seebeck coefficient, and the power factor of the four materials above based on parameters obtained from first-principles calculations and using several other fitting parameters. For quaternary compounds, our results reveal that Cu2ZnSnSe4 is better than Cu2ZnSnS4 and its optimal hole concentration is around 5 ×1019cm-3 with the peak power factor 4.7 μ W/cm K 2 at 600 K. For ternary compounds, we find that their optimal hole concentrations are around 1 ×1020cm-3 with the peak power factors over 26 μ W/cm K 2 at 800 K.

  7. Photonic-Crystal-Based Thin Film Sensor for Detecting Volatile Organic Compounds

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Hyung Kwan; Park, Jung Yul [Sogang Univ., Seoul (Korea, Republic of)


    Early detection of toxic gases, such as volatile organic compounds (VOCs), is important for safety and environmental protection. However, the conventional detection methods require long-term measurement times and expensive equipment. In this study, we propose a thin-film-type chemical sensor for VOCs, which consists of self assembled monosize nanoparticles for 3-D photonic crystal structures and polydimthylsiloxane (PDMS) film. It is operated without any external power source, is truly portable, and has a fast response time. The structure color of the sensor changes when it is exposed to VOCs, because VOCs induce a swelling of the PDMS. Therefore, using this principle of color change, we can create a thin-film sensor for immediate detection of various types of VOCs. The proposed device evidences that a fast response time of just seconds, along with a clear color change, are successfully observed when the sensor is exposed to gas-phase VOCs.

  8. Metabolomics-Based Screening of Biofilm-Inhibitory Compounds against Pseudomonas aeruginosa from Burdock Leaf

    Directory of Open Access Journals (Sweden)

    Zaixiang Lou


    Full Text Available Screening of anti-biofilm compounds from the burdock leaf based on metabolomics is reported here. The crystal violet assay indicated 34% ethanol elution fraction of burdock leaf could completely inhibit biofilm formation of Pseudomonas aeruginosa at 1 mg·mL−1. Then, the chemical composition of burdock leaf fraction was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS and 11 active compounds (chlorogenic acid, caffeic acid, p-coumaric acid, quercetin, ursolic acid, rutin, cynarin, luteolin, crocin, benzoic acid, and Tenacissoside I were identified. Lastly, UPLC-MS analysis was employed to obtain the metabolic fingerprints of burdock leaf fractions before and after inhibiting the biofilm of Pseudomonas aeruginosa. The metabolic fingerprints were transformed to data, analyzed with PLS-DA (partial least squares discriminant analysis and the peaks whose area was significantly changed were found out. Thus, 81 compounds were screened as potential anti-biofilm ingredients. Among them, rutin, ursolic acid, caffeic acid, p-coumaric acid and quercetin were identified and confirmed as the main anti-biofilm compounds in burdock leaf. The study provided basic anti-biofilm profile data for the compounds in burdock leaf, as well as provided a convenient method for fast screening of anti-biofilm compounds from natural plants.

  9. Microwave assisted synthesis of 2-pyridone and 2-pyridone based compounds

    Directory of Open Access Journals (Sweden)

    Mijin Dušan Ž.


    Full Text Available 2-Pyridones are important heterocyclic compounds that are widely used in medical chemistry, and their various derivatives have significant biological and medical applications. In this paper, the synthesis of 2-pyridones as well as 2-pyridone based compounds such as 2-quinolones using microwave assisted organic chemistry is reviewed. The review is divided in three parts. In the first part, microwave synthesis of 2-pyridones according to the type of condensation is discussed. In the second part, microwave assisted synthesis of 2-quionolones is listed. At the end of the review several examples of microwave synthesis of other 2-pyridone based compounds (ring fused N-substituted 2-pyridones are given. [Projekat Ministarstva nauke Republike Srbije, br. 172013

  10. Biodegradability and toxicity of sulphonate-based surfactants in aerobic and anaerobic aquatic environments. (United States)

    García, M T; Campos, E; Marsal, A; Ribosa, I


    Four types of commonly used sulphonate-based surfactants (alkane sulphonates, alpha-olefin sulphonates, sulphosuccinates and methyl ester sulphonates) were tested for their aerobic and anaerobic biodegradability as well as for their toxicity to Daphnia magna and Photobacterium phosphoreum to assess the effect of the surfactant structure on those properties. Aerobic biodegradation was evaluated by means of the CO2 headspace test and anaerobic biodegradation was assessed by a method based on the ECETOC test. All the surfactants tested were readily biodegraded under aerobic conditions. No clear effect of the surfactant structures on the toxicity to the aquatic organisms tested was found. The most significant differences in the surfactants studied were observed in their behaviour under anaerobic conditions. Alkane sulphonates, alpha-olefin sulphonates and methyl ester sulphonates were not mineralized in lab anaerobic digesters despite the fact that the last one showed a certain degree of primary degradation. Nevertheless, these surfactants did not significantly inhibit methanogenic activity at concentrations up to 15 g surfactant/kg dry sludge, a concentration that is much higher than the expected concentrations of these surfactants in real anaerobic digesters. Sulphosuccinates showed a high level of primary biodegradation in anaerobic conditions. However, linear alkyl sulphosuccinates were completely mineralized whereas branched alkyl sulphosuccinates achieved percentages of ultimate biodegradation < or =50%.

  11. Analysis of Toxicity of Ceramic Nanoparticles and Functional Nanocomposites Based on Vulcanized Natural Rubber

    Directory of Open Access Journals (Sweden)

    Bellucci Felipe Silva


    Full Text Available Nanocomposites are multiphase materials of which, at least one of the phases, has a dimension smaller than 100 nm. These materials have attracted technological and scientific interest due to their multifunctional characteristics and potential, which allow them to combine unique properties which are not found in traditional commercial materials, such as natural rubber alone. The objective of this work is to analyse the toxicity of nanoparticles and nanocomposites when applied to mammal cells in order to obtain bioactive agents, as well as to evaluate the potential to be applied in biological systems. Ferroelectric ceramic nanoparticles of KSr2Nb5O15 (KSN and paramagnetic ceramic nanoparticles Ni0.5Zn0.5Fe2O4 (NZF were prepared and utilized to produce functional and multifunctional nanocomposites based on vulcanized natural rubber (NR/KSN and NR/NZF with different nanoparticle concentrations. For both kinds of nanoparticles and both classes of nanocomposites, independently of the nanoparticle concentration, it is not possible to observe any reduction of the cellular viability until the incubation time is finished. In this way, these results point to the possibility of using these nanoparticles and nanocomposites, from the toxicity point of view, as bioactivity agents in biological systems based on mammalian cells.

  12. Synthesis and preliminary biological evaluation of a small library of hybrid compounds based on Ugi isocyanide multicomponent reactions with a marine natural product scaffold. (United States)

    Avilés, Edward; Prudhomme, Jacques; Le Roch, Karine G; Franzblau, Scott G; Chandrasena, Kevin; Mayer, Alejandro M S; Rodríguez, Abimael D


    A mixture-based combinatorial library of five Ugi adducts (4-8) incorporating known antitubercular and antimalarial pharmacophores was successfully synthesized, starting from the naturally occurring diisocyanide 3, via parallel Ugi four-center three-component reactions (U-4C-3CR). The novel α-acylamino amides obtained were evaluated for their antiinfective potential against laboratory strains of Mycobacterium tuberculosis H37Rv and chloroquine-susceptible 3D7 Plasmodium falciparum. Interestingly, compounds 4-8 displayed potent in vitro antiparasitic activity with higher cytotoxicity in comparison to their diisocyanide precursor 3, with the best compound exhibiting an IC50 value of 3.6 nM. Additionally, these natural product inspired hybrids potently inhibited in vitro thromboxane B2 (TXB2) and superoxide anion (O2(-)) generation from Escherichia coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with concomitant low short-term toxicity.

  13. Iron-Based Nanoparticles for Toxic Organic Degradation: Silica Platform and Green Synthesis. (United States)

    Meeks, Noah D; Smuleac, Vasile; Stevens, Christopher; Bhattacharyya, Dibakar


    Iron and iron oxide nanoparticles (NPs) are finding wide applications for the remediation of various toxic chloro-organic compounds (such as trichloroethylene, TCE), via reductive and oxidative processes. In this study, Fe NPs (30-50 nm) are synthesized by reduction from ferric ions immobilized (by ion exchange) on a platform (two types of sulfonated silica particles), in order to prevent the NP agglomeration. Next, the Fe NPs are oxidized and their effectiveness for the oxidative dechlorination of TCE via the heterogeneous decomposition of hydrogen peroxide to OH• on the surface of the iron oxide NPs was demonstrated. For the reductive approach, the use of ascorbic acid as a "green" reducing agent in conjunction with a secondary metal (Pd) inhibits NP oxidation and agglomeration through surface adsorbed species. The Fe/Pd NPs have been successfully applied for the dechlorination of TCE (k(SA), surface-area normalized reaction rate, = 8.1 ×10(-4) L/m(2)h).

  14. Contact-based ligand-clustering approach for the identification of active compounds in virtual screening

    Directory of Open Access Journals (Sweden)

    Mantsyzov AB


    Full Text Available Alexey B Mantsyzov,1 Guillaume Bouvier,2 Nathalie Evrard-Todeschi,1 Gildas Bertho11Université Paris Descartes, Sorbonne, Paris, France; 2Institut Pasteur, Paris, FranceAbstract: Evaluation of docking results is one of the most important problems for virtual screening and in silico drug design. Modern approaches for the identification of active compounds in a large data set of docked molecules use energy scoring functions. One of the general and most significant limitations of these methods relates to inaccurate binding energy estimation, which results in false scoring of docked compounds. Automatic analysis of poses using self-organizing maps (AuPosSOM represents an alternative approach for the evaluation of docking results based on the clustering of compounds by the similarity of their contacts with the receptor. A scoring function was developed for the identification of the active compounds in the AuPosSOM clustered dataset. In addition, the AuPosSOM efficiency for the clustering of compounds and the identification of key contacts considered as important for its activity, were also improved. Benchmark tests for several targets revealed that together with the developed scoring function, AuPosSOM represents a good alternative to the energy-based scoring functions for the evaluation of docking results.Keywords: scoring, docking, virtual screening, CAR, AuPosSOM

  15. Comparative short-term inhalation toxicity of five organic diketopyrrolopyrrole pigments and two inorganic iron-oxide-based pigments (United States)

    Hofmann, Thomas; Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Rey Moreno, Maria; Neubauer, Nicole; Wohlleben, Wendel; Gröters, Sibylle; Wiench, Karin; Veith, Ulrich; Teubner, Wera; van Ravenzwaay, Bennard; Landsiedel, Robert


    Abstract Diketopyrrolopyrroles (DPP) are a relatively new class of organic high-performance pigments. The present inhalation and particle characterization studies were performed to compare the effects of five DPP-based pigments (coarse and fine Pigment Red 254, coarse and fine meta-chloro DPP isomer and one form of mixed chlorinated DPP isomers) and compare it to coarse and fine inorganic Pigment Red 101. Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 h/day on 5 consecutive days. Target concentrations were 30 mg/m3 as high dose for all compounds and selected based occupational exposure limits for respirable nuisance dust. Toxicity was determined after end of exposure and after 3-week recovery using broncho-alveolar lavage fluid (BALF) and microscopic examinations of the entire respiratory tract. Mixed chlorinated DPP isomers and coarse meta-chloro DPP isomer caused marginal changes in BALF, consisting of slight increases of polymorphonuclear neutrophils, and in case of coarse meta-chloro DPP increased MCP-1 and osteopontin levels. Mixed chlorinated DPP isomers, Pigment Red 254, and meta-chloro DPP caused pigment deposits and phagocytosis by alveolar macrophages, slight hypertrophy/hyperplasia of the bronchioles and alveolar ducts, but without evidence of inflammation. In contrast, only pigment deposition and pigment phagocytosis were observed after exposure to Pigment Red 101. All pigments were tolerated well and caused only marginal effects in BALF or no effects at all. Only minor effects were seen on the lung by microscopic examination. There was no evidence of systemic inflammation based on acute-phase protein levels in blood. PMID:27387137

  16. Ab-initio modeling of an anion $C_{60}^-$ pseudopotential for fullerene-based compounds

    CERN Document Server

    Vrubel, I I; Ivanov, V K


    A pseudopotential of $C_{60}^-$ has been constructed from ab-initio quantum-mechanical calculations. Since the obtained pseudopotential can be easily fitted by rather simple analytical approximation it can be effectively used both in classical and quantum molecular dynamics of fullerene-based compounds.

  17. Compound parabolic concentrator optical fiber tip for FRET-based fluorescent sensors

    DEFF Research Database (Denmark)

    Hassan, Hafeez Ul; Nielsen, Kristian; Aasmul, Soren


    The Compound Parabolic Concentrator (CPC) optical fiber tip shape has been proposed for intensity based fluorescent sensors working on the principle of FRET (Förster Resonance Energy Transfer). A simple numerical Zemax model has been used to optimize the CPC tip geometry for a step-index multimod...

  18. Normalization references for USEtoxTM-based toxic impact categories: North American and European economic systems

    DEFF Research Database (Denmark)

    Laurent, Alexis; Lautier, Anne; Rosenbaum, Ralph K.


    economic regions, North America and Europe, to calculate normalization references for the three currently-modelled USEtoxTM-based impact categories, i.e. freshwater ecotoxicity, human toxicity, divided into cancer effects and non-cancer effects. Base years for the references are 2004 for Europe and 2006...... coverage of organics in both the inventory and the CF databases. With respect to the intended global character of the USEtoxTM model, different approaches to determine normalization references of other economic systems (e.g. Asia or world) are discussed in relation to these findings. Overall, we thus...... recommend the use of the provided set of normalization references for USEtoxTM, but we also advocate 1) to perform an update as soon as a more comprehensive inventory can be obtained and as soon as characterization factors for metals are revised; 2) to consider extension to other economic systems in order...

  19. Normalization references for USEtoxTM-based toxic impact categories: North American and European economic systems

    DEFF Research Database (Denmark)

    Laurent, Alexis; Lautier, Anne; Rosenbaum, Ralph K.


    coverage of organics in both the inventory and the CF databases. With respect to the intended global character of the USEtoxTM model, different approaches to determine normalization references of other economic systems (e.g. Asia or world) are discussed in relation to these findings. Overall, we thus...... economic regions, North America and Europe, to calculate normalization references for the three currently-modelled USEtoxTM-based impact categories, i.e. freshwater ecotoxicity, human toxicity, divided into cancer effects and non-cancer effects. Base years for the references are 2004 for Europe and 2006...... recommend the use of the provided set of normalization references for USEtoxTM, but we also advocate 1) to perform an update as soon as a more comprehensive inventory can be obtained and as soon as characterization factors for metals are revised; 2) to consider extension to other economic systems in order...

  20. Amoebae-Based Screening Reveals a Novel Family of Compounds Restricting Intracellular Legionella pneumophila. (United States)

    Harrison, Christopher F; Chiriano, Gianpaolo; Finsel, Ivo; Manske, Christian; Hoffmann, Christine; Steiner, Bernhard; Kranjc, Agata; Patthey-Vuadens, Ophelie; Kicka, Sébastien; Trofimov, Valentin; Ouertatani-Sakouhi, Hajer; Soldati, Thierry; Scapozza, Leonardo; Hilbi, Hubert


    The causative agent of Legionnaires' disease, Legionella pneumophila, grows in environmental amoebae and mammalian macrophages within a distinct compartment, the 'Legionella-containing vacuole' (LCV). Intracellular bacteria are protected from many antibiotics, and thus are notoriously difficult to eradicate. To identify novel compounds that restrict intracellular bacterial replication, we previously developed an assay based on a coculture of amoebae and GFP-producing L. pneumophila. This assay was used to screen a pathway-based, highly diverse chemical library, referred to as the Sinergia library. In this work, we chose to focus on a group of 11 hit compounds, the majority of which originated from the query molecule CN585, a compound that targets the protein phosphatase calcineurin. Further studies on 78 related compound variants revealed crucial structural attributes, namely a triple-ring scaffold with a central triazine moiety, substituted in positions 3 and 5 by two piperidine or pyrrolidine rings, and in position 1 by an amine group bearing a single aliphatic chain moiety. The most effective compound, ZINC00615682, inhibited intracellular replication of L. pneumophila with an IC50 of approximately 20 nM in Acanthamoeba castellanii and slightly less efficiently in Dictyostelium discoideum or macrophages. Pharmacological and genetic attempts to implicate calcineurin in the intracellular replication of L. pneumophila failed. Taken together, these results show that the amoebae-based screen and structure-activity relationship analysis is suitable for the identification of novel inhibitors of the intracellular replication of L. pneumophila. The most potent compound identified in this study targets (an) as yet unidentified host factor(s).

  1. Coating carbon nanotubes with a polystyrene-based polymer protects against pulmonary toxicity

    Directory of Open Access Journals (Sweden)

    Rossi Michel J


    Full Text Available Abstract Background carbon nanotubes (CNT can have adverse effects on health. Therefore, minimizing the risk associated with CNT exposure is of crucial importance. The aim of this work was to evaluate if coating multi-walled CNT (MWCNT with polymers could modify their toxicity, thus representing a useful strategy to decrease adverse health effects of CNT. We used industrially-produced MWCNT uncoated (NT1 or coated (50/50 wt% with acid-based (NT2 or polystyrene-based (NT3 polymer, and exposed murine macrophages (RAW 264.7 cell line or Balb/c mice by intratracheal administration. Biological experiments were performed both in vitro and in vivo, examining time- and dose-dependent effects of CNT, in terms of cytotoxicity, expression of genes and proteins related to oxidative stress, inflammation and tissue remodeling, cell and lung tissue morphology (optical and transmission electron microscopy, and bronchoalveolar lavage fluid content analysis. Results extensive physico-chemical characterization of MWCNT was performed, and showed, although similar dimensions for the 3 MWCNT, a much smaller specific surface area for NT2 and NT3 as compared to NT1 (54.1, 34 and 227.54 m2/g respectively, along with different surface characteristics. MWCNT-induced cytotoxicity, oxidative stress, and inflammation were increased by acid-based and decreased by polystyrene-based polymer coating both in vitro in murine macrophages and in vivo in lung of mice monitored for 6 months. Conclusions these results demonstrate that coating CNT with polymers, without affecting their intrinsic structure, may constitute a useful strategy for decreasing CNT toxicity, and may hold promise for improving occupational safety and that of general the user.

  2. New color image encryption algorithm based on compound chaos mapping and hyperchaotic cellular neural network (United States)

    Li, Jinqing; Bai, Fengming; Di, Xiaoqiang


    We propose an image encryption/decryption algorithm based on chaotic control parameter and hyperchaotic system with the composite permutation-diffusion structure. Compound chaos mapping is used to generate control parameters in the permutation stage. The high correlation between pixels is shuffled. In the diffusion stage, compound chaos mapping of different initial condition and control parameter generates the diffusion parameters, which are applied to hyperchaotic cellular neural networks. The diffusion key stream is obtained by this process and implements the pixels' diffusion. Compared with the existing methods, both simulation and statistical analysis of our proposed algorithm show that the algorithm has a good performance against attacks and meets the corresponding security level.

  3. Single crystal growth of europium and ytterbium based intermetallic compounds using metal flux technique

    Indian Academy of Sciences (India)

    Sumanta Sarkar; Sebastian C Peter


    This article covers the use of indium as a potential metal solvent for the crystal growth of europium and ytterbium-based intermetallic compounds. A brief view about the advantage of metal flux technique and the use of indium as reactive and non-reactive flux are outlined. Large single crystals of EuGe2, EuCoGe3 and Yb2AuGe3 compounds were obtained in high yield from the reactions of the elements in liquid indium. The results presented here demonstrate that considerable advances in the discovery of single crystal growth of complex phases are achievable utilizing molten metals as solvents.

  4. tcTKB: an integrated cardiovascular toxicity knowledge base for targeted cancer drugs (United States)

    Xu, Rong; Wang, QuanQiu


    Targeted cancer drugs are often associated with unexpectedly high cardiovascular (CV) adverse events. Systematic approaches to studying CV events associated with targeted anticancer drugs have high potential for elucidating the complex pathways underlying targeted anti-cancer drugs. In this study, we built tcTKB, a comprehensive CV toxicity knowledge base for targeted cancer drugs, by extracting drug-CV pairs from five large-scale and complementary data sources. The data sources include FDA drug labels (44,979 labels), the FDA Adverse Event Reporting System (FAERS) (4,285,097 records), the Canada Vigilance Adverse Reaction Online Database (CVAROD) (1,107,752 records), published biomedical literature (21,354,075 records), and published full-text articles from the Journal of Oncology (JCO) (13,855 articles). tcTKB contains 14,351 drug-CV pairs for 45 targeted anticancer drugs and 1,842 CV events. We demonstrate that CV events positively correlate with drug target genes and drug metabolism genes, demonstrating that tcTKB in combination with other data resources, could facilitate our understanding of targeted anticancer drugs and their associated CV toxicities. PMID:26958275

  5. Toxicity study of water transferred graphene-based nanostructures for cell culture substrate (United States)

    Borghi, Fabricio; van der Laan, Tim; Ishaq, Musarat; Kumar, Shailesh; Ostrikov, Kostya


    Graphene has attracted enormous attention due to its unique physical and chemical properties. Early researches had focused on it electrical properties for device applications. Nowadays graphene has attracted increased interest in bio-medical applications, such as cell culture substrates. Substrates are critical for: investigating early stage development of cells, new drugs tests and tissue engineering. Benefits of graphene for this application are: it can be produced with desired structural morphology, its surface properties can be modified via plasma or chemical treatment (decorated with specific functional groups), and it can be transferred to a plethora of substrates (high influence of cells fate). Successful applications of graphene-based materials for bio-med applications are predominantly produced via chemical methods. When produced via Thermal CVD, the transfer to the desired substrate involves chemical treatment, potentially contaminating the graphene. In this work, we use a unique plasma produced graphene, transferred to glass via a chemical-free process, as cell culture substrates. This work aims graphene's bio-toxicity. Our results show that our material is non toxic, and cells morphology and proliferation indicates similar growth among all samples and the control.

  6. Scenario-based prediction of Li-ion batteries fire-induced toxicity (United States)

    Lecocq, Amandine; Eshetu, Gebrekidan Gebresilassie; Grugeon, Sylvie; Martin, Nelly; Laruelle, Stephane; Marlair, Guy


    The development of high energy Li-ion batteries with improved durability and increased safety mostly relies on the use of newly developed electrolytes. A detailed appraisal of fire-induced thermal and chemical threats on LiPF6- and LiFSI-based electrolytes by means of the so-called "fire propagation apparatus" had highlighted that the salt anion was responsible for the emission of a non negligible content of irritant gas as HF (PF6-) or HF and SO2 (FSI-). A more thorough comparative investigation of the toxicity threat in the case of larger-size 0.4 kWh Li-ion modules was thus undertaken. A modeling approach that consists in extrapolating the experimental data obtained from 1.3Ah LiFePO4/graphite pouch cells under fire conditions and in using the state-of-the-art fire safety international standards for the evaluation of fire toxicity was applied under two different real-scale simulating scenarios. The obtained results reveal that critical thresholds are highly dependent on the nature of the salt, LiPF6 or LiFSI, and on the cells state of charge. Hence, this approach can help define appropriate fire safety engineering measures for a given technology (different chemistry) or application (fully charged backup batteries or batteries subjected to deep discharge).

  7. Toxic effects of Al-based coagulants on Brassica chinensis and Raphanus sativus growing in acid and neutral conditions. (United States)

    Zhang, Kaisong; Zhou, Qixing


    The ecotoxicological effects of aluminum (Al)-based coagulants are of concern because of their wide-ranging applications in wastewater treatment and water purification. As important Al-based coagulants, AlCl(3) and PAC (polyaluminum-chloride) were selected as examples to examine the toxic effects on representative vegetables including the cabbage Brassica chinensis and the radish Raphanus sativus over a range of exposure concentrations in neutral (pH 7.00) and acidic (pH 4.00) conditions, using seed germination and root elongation in the early-growth stage as indicators of toxicity. The results showed that root elongation of the two vegetables was a more sensitive indicator than was seed germination for evaluating the toxicity of Al. As a single influencing factor, H(+) had no significant direct effects on root elongation of Brassica chinensis and Raphanus sativus under the experimental conditions. The toxicity of Al played the main role in inhibiting root elongation and seed germination and was strongly related to changes in pH. There was a markedly positive relationship between the inhibitory rate of root elongation, seed germination, and the concentration of Al at pH 4.00 (p < 0.01). The toxic effect of AlCl(3) on Brassica chinensis was less with a neutral pH than at pH 4.00, but Raphanus sativus was more susceptible to AlCl(3) toxicity at a neutral pH than at pH 4.00. Both Raphanus sativus and Brassica chinensis had a more toxic response to a low concentration (<64 mg . L(-1)) of PAC in a neutral condition than in an acidic condition. Undoubtedly, the Al toxicity caused by Al-based coagulants at a neutral pH is relevant when treatment solids are used in agriculture.

  8. A flow cytometer-based method to simultaneously assess activity and selectivity of compounds against the intracellular forms of Trypanosoma cruzi. (United States)

    Miranda, Cristian Gabriel; Solana, Maria Elisa; Curto, Maria de Los Angeles; Lammel, Estela Maria; Schijman, Alejandro Gabriel; Alba Soto, Catalina Dirney


    Chagas disease is a major unsolved health issue in Latin America and an emerging threat worldwide. New drugs are urgently needed for chemotherapy as those available (benznidazole and nifurtimox) have variable efficacy and elevated toxicity. Efforts are actually oriented to improve tools and technologies (e.g. transgenic parasites, flow cytometry or image-based systems) for the screening of large numbers of candidate compounds for their activity against Trypanosoma cruzi (T. cruzi). Methods that test drug efficacy and selectivity in the same assay are suitable to accelerate the process of drug discovery. Here, we developed a GFP expressing T. cruzi from a moderate virulence stock and confirmed that the transgenic parasite retained the biological characteristics of the parental strain. With this tool, we established a flow cytometer-based method to simultaneously test drug activity against intracellular amastigotes and toxicity to the host cell. This one-step procedure allows determining the selectivity index of the tested compound in a sensitive and accurate manner even with low infection rates. This method can provide additional information on the interactions between drug, parasites and host cell and could be adapted to other trypanosomatids and protozoa with intracellular multiplication.

  9. Multipurpose Compound (United States)


    Specially formulated derivatives of an unusual basic compound known as Alcide may be the answer to effective treatment and prevention of the disease bovine mastitis, a bacterial inflammation of a cow's mammary gland that results in loss of milk production and in extreme cases, death. Manufactured by Alcide Corporation the Alcide compound has killed all tested bacteria, virus and fungi, shortly after contact, with minimal toxic effects on humans or animals. Alcide Corporation credits the existence of the mastitis treatment/prevention products to assistance provided the company by NERAC, Inc.

  10. Syntheses and Supramolecular Structures of Two Nickel(Ⅱ) Compounds Based on Two Thiosemicarbazone Ligands

    Institute of Scientific and Technical Information of China (English)

    LI Cheng-juan; FENG Ze-jing; ZHAO Xiao-juan; WANG Su-na; DOU Jian-min


    Two new compounds,[Ni2(L1)(Py)6]Py·CH3OH(1) and [Ni3(L2)2(Py)4]·2DMF(2)(H4L1=N,N'-bisalicylbisthiocarbamide; H3L2=3-hydroxyl-2-naphthalene thiosemicarbazide; Py=pyridine; DMF=dimethyl fumarate),based upon two thiosemicarbazone ligands have been obtained and characterized by elemental analysis,Fourier transform infrared(FTIR) and X-ray diffraction(XRD).Compound 1 possesses a binuclear cluster,in which the bisalicylbisthiocarbamide acts as a hexadentate bridge.Compound 2 exhibits a linear trinuclear cluster with the triply-deprotonated ligand acting as pentadentate bridge.C—H…O,C—H…π and C—H…S weak interactions further link these molecules to form interesting supramolecular networks.

  11. Two-and three-photon absorption in a novel fluorene-based compound

    Institute of Scientific and Technical Information of China (English)

    Wenbo Ma; Yiqun Wu; Donghong Gu; Fuxi Gan


    @@ A novel symmetrical charge transfer fluorene-based compound 2,7-bis (4-methoxystyryl)-9, 9-bis (2-ethylhexyl)-9H-fluorene (abbreviated as BMOSF) was synthesized and its nonlinear absorption was investigated using two different laser systems: a 140-fs, 800-nm Ti:sapphire laser operating at 1-kHz repetition rate and a 38-ps, 1064-nm Nd:YAG pulsed laser operating at 10-Hz repetition rate, respectively. Unique nonlinear absorption properties in this new compound were observed that rise from multiphoton absorption. The nonlinear absorption coefficients were measured to be 6.02 × 10-3 cm/GW (due to two-photon absorption, exciting wavelength is 800 nm) and 3.6×10-20 cm3/W2 (due to three-photon absorption, exciting wavelength is 1064 nm). This new compound possesses strong fluorescence induced by two-photon absorption and obvious three-photon absorption optical limiting effects.

  12. Thermoelectric Properties of ZrNiSn-Based Half-Heusler Compounds (United States)

    Yang, Jihui


    An increasing awareness of energy efficiency and environmental concerns has rekindled prospects for automotive and other applications of thermoelectric materials. For instance, getting “free” electric power from waste heat or obtaining cooling power from a solid-state device is very appealing for the automotive industry. ZrNiSn-based half-Heusler compounds show promising transport properties that make these materials of interest for thermoelectric power generation. The talk will focus on the effect on transport properties of alloying and doping on the various sublattices. New high temperature data will be presented that indicate that appropriately modified half-Heusler compounds possess very high power factor and relatively low thermal conductivity, leading to a dimensionless thermoelectric figure of merit ZT of 0.7 at 800 K. This is the highest ZT value for any half-Heusler compound reported so far.

  13. Multifractal entropy based adaptive multiwavelet construction and its application for mechanical compound-fault diagnosis (United States)

    He, Shuilong; Chen, Jinglong; Zhou, Zitong; Zi, Yanyang; Wang, Yanxue; Wang, Xiaodong


    Compound-fault diagnosis of mechanical equipment is still challenging at present because of its complexity, multiplicity and non-stationarity. In this work, an adaptive redundant multiwavelet packet (ARMP) method is proposed for the compound-fault diagnosis. Multiwavelet transform has two or more base functions and many excellent properties, making it suitable for detecting all the features of compound-fault simultaneously. However, on the other hand, the fixed basis function used in multiwavelet transform may decrease the accuracy of fault extraction; what's more, the multi-resolution analysis of multiwavelet transform in low frequency band may also leave out the useful features. Thus, the minimum sum of normalized multifractal entropy is adopted as the optimization criteria for the proposed ARMP method, while the relative energy ratio of the characteristic frequency is utilized as an effective way in automatically selecting the sensitive frequency bands. Then, The ARMP technique combined with Hilbert transform demodulation analysis is then applied to detect the compound-fault of bevel gearbox and planetary gearbox. The results verify that the proposed method can effectively identify and detect the compound-fault of mechanical equipment.

  14. Phytobioactive compound-based nanodelivery systems for the treatment of type 2 diabetes mellitus - current status. (United States)

    Ganesan, Palanivel; Arulselvan, Palanisamy; Choi, Dong-Kug


    Type 2 diabetes mellitus (T2DM) is a major chronic disease that is prevalent worldwide, and it is characterized by an increase in blood glucose, disturbances in the metabolism, and alteration in insulin secretion. Nowadays, food-based therapy has become an important treatment mode for type 2 diabetes, and phytobioactive compounds have gained an increasing amount of attention to this end because they have an effect on multiple biological functions, including the sustained secretion of insulin and regeneration of pancreatic islets cells. However, the poor solubility and lower permeability of these phyto products results in a loss of bioactivity during processing and oral delivery, leading to a significant reduction in the bioavailability of phytobioactive compounds to treat T2DM. Recently, nanotechnological systems have been developed for use as various types of carrier systems to improve the delivery of bioactive compounds and thus obtain a greater bioavailability. Furthermore, carrier systems in most nanodelivery systems are highly biocompatible, with nonimmunologic behavior, a high degree of biodegradability, and greater mucoadhesive strength. Therefore, this review focuses on the various types of nanodelivery systems that can be used for phytobioactive compounds in treating T2DM with greater antidiabetic effects. There is also additional focus on improving the effects of various phytobioactive compounds through nanotechnological delivery to ensure a highly efficient treatment of type 2 diabetes.

  15. Solving the problem of structure determination in 3d transition metal based Heusler compounds

    Energy Technology Data Exchange (ETDEWEB)

    Balke, Benjamin; Fecher, Gerhard H.; Blum, Christian; Basit, Lubna; Felser, Claudia [Institute of Inorganic and Analytical Chemistry, Johannes Gutenberg - University, Mainz (Germany)


    This work reports on the structural investigation of Fe-containing, Co{sub 2}-based Heusler compounds (Co{sub 2}FeZ with Z=Al, Si, Ga, Ge) using anomalous X-ray diffraction (XRD) and extended X-ray absorption fine structure spectroscopy (EXAFS). Using XRD, it was shown that Co{sub 2}FeAl crystallizes in the B2 structure whereas Co{sub 2}FeSi crystallizes in the L2{sub 1} structure. For compounds containing Ga or Ge, the XRD technique with regular laboratory sources for excitation can not be used easily to distinguish the two structures. For this reason, EXAFS was used to elucidate the structure of these two compounds. The absorption experiments close to the K-edges of Co, Fe, Ga, and Ge indicated that both compounds crystallize in the L2{sub 1} structure. Exciting the XRD at the K-edges of Co and Fe leads to anomalous X-ray scattering. The dependence of the scattering parameters on the energy close to the absorption edges was used to identify the L2{sub 1} structure of the Ga and Ge containing compounds unambiguously. The applicability of the techniques on nano-scaled materials is demonstrated for the example of Co{sub 2}FeGa nano-particles with sizes of below 25 nm.

  16. Development of diagnostic SPR based biosensor for the detection of pharmaceutical compounds in saliva (United States)

    Sonny, Susanna; Sesay, Adama M.; Virtanen, Vesa


    The aim of the study is to develop diagnostic tests for the detection of pharmaceutical compounds in saliva. Oral fluid is increasingly being considered as an ideal sample matrix. It can be collected non-invasively and causes less stress to the person being tested. The detection of pharmaceutical compounds and drugs in saliva can give valuable information on individual bases on dose response, usage, characterization and clinical diagnostics. Surface plasmon resonance (SPR) is a highly sensitive, fast and label free analytical technique for the detection of molecular interactions. The specific binding of measured analyte onto the active gold sensing surface of the SPR device induces a refractive index change that can be monitored. To monitor these pharmaceutical compounds in saliva the immunoassays were developed using a SPR instrument. The instrument is equipped with a 670nm laser diode and has two sensing channels. Monoclonal antibodies against the pharmaceutical compounds were used to specifically recognise and capture the compounds which intern will have an effect of the refractive index monitored. Preliminary results show that the immunoassays for cocaine and MDMA (3,4-methylenedioxymethamphetamine) are very sensitive and have linear ranges of 0.01 pg/ml - 1 ng/ml and 0.1 pg/ml - 100 ng/ml, respectively.

  17. Impact of Insecticide Resistance on the Effectiveness of Pyrethroid-Based Malaria Vectors Control Tools in Benin: Decreased Toxicity and Repellent Effect.

    Directory of Open Access Journals (Sweden)

    Fiacre R Agossa

    Full Text Available Since the first evidence of pyrethroids resistance in 1999 in Benin, mutations have rapidly increased in mosquitoes and it is now difficult to design a study including a control area where malaria vectors are fully susceptible. Few studies have assessed the after effect of resistance on the success of pyrethroid based prevention methods in mosquito populations. We therefore assessed the impact of resistance on the effectiveness of pyrethroids based indoor residual spraying (IRS in semi-field conditions and long lasting insecticidal nets (LLINs in laboratory conditions. The results observed showed low repulsion and low toxicity of pyrethroids compounds in the test populations. The toxicity of pyrethroids used in IRS was significantly low with An. gambiae s.l (< 46% but high for other predominant species such as Mansonia africana (93% to 97%. There were significant differences in terms of the repellent effect expressed as exophily and deterrence compared to the untreated huts (P<0.001. Furthermore, mortality was 23.71% for OlyseNet® and 39.06% for PermaNet®. However, with laboratory susceptible "Kisumu", mortality was 100% for both nets suggesting a resistance within the wild mosquito populations. Thus treatment with pyrethroids at World Health Organization recommended dose will not be effective at reducing malaria in the coming years. Therefore it is necessary to study how insecticide resistance decreases the efficacy of particular pyrethroids used in pyrethroid-based vector control so that a targeted approach can be adopted.

  18. Design, construction and testing of a system for detection of toxic gases based on piezoelectric crystals. (United States)

    Leyva, J A; de Cisneros, J L; de Barreda, D G; Becerra, A J


    A system for static operation of toxic gas sensors based on piezoelectric crystals was constructed as a preliminary step in the development of this type of sensor. The sensing part of the setup consists of a twin oscillating circuit assembled from commercially available electronic parts mounted on a motherboard. The oscillating circuits can accommodate two piezoelectric crystals, of which one or both can be coated with different materials, or a single one, as required. The sensing assembly (crystals plus oscillating circuits) is placed in a customized test chamber that allows one to control and reproduce its internal environment. Once assembled and fine-tuned, the proposed setup was used to test a commercially available piezoelectric crystal for sensing formaldehyde in order to expand available information on this type of sensor.

  19. Soil microbial toxicity assessment of a copper-based fungicide in two contrasting soils (United States)

    Dober, Melanie; Deltedesco, Evi; Jöchlinger, Lisa; Schneider, Martin; Gorfer, Markus; Bruckner, Alexander; Zechmeister-Boltenstern, Sophie; Soja, Gerhard; Zehetner, Franz; Keiblinger, Katharina Maria


    The infestation with the fungus downy mildew (Plasmopara viticola) causes dramatic losses in wine production. Copper (Cu) based fungicides have been used in viticulture since the end of the 19th century, and until today both conventional and organic viticulture strongly rely on Cu to prevent and reduce fungal diseases. Consequently, Cu has built up in many vineyard soils and it is still unclear how this affects soil functioning. The aim of the present study is the evaluation of the soil microbial toxicity of Cu contamination. Two contrasting agricultural soils, an acidic sandy soil and a calcareous loamy soil, were sampled to conduct an eco-toxicological greenhouse pot experiment. The soils were spiked with a commonly used fungicide based on copper hydroxid in seven concentrations (0, 50, 100, 200, 500, 1500 and 5000 mg Cu kg-1 soil) and Lucerne (Medicago sativa L. cultivar. Plato) was grown in the pots for 3 months. Sampling was conducted at the beginning and at the end of the study period to test copper's soil microbial toxicity in total microbial biomass and basal respiration, as well as enzyme activities, such as exoglucanase, β-glucosidase, exochitinase, phosphatase, protease, phenol-, peroxidase and urease. Additionally, DOC, TN, Cmic, Nmic, NO3 and NH4 were determined to provide further insight into the carbon and nitrogen cycle. Microbial community structure was analysed by phospholipid fatty acids (PLFAs), and ergosterol as a fungal biomarker. In addition, molecular tools were applied by extracting soil DNA and performing real time quantitative polymerase chain reaction (qPCR) and a metagenomic approach using 16S and ITS amplification and sequencing with MiSeq platform for the second sampling. Hydrolytic extracellular enzymes were not clearly affected by rising Cu concentrations, while a trend of increasing activity of oxidative enzymes (phenol- and peroxidase) was observed. Microbial respiration rate as well as the amount of Cmic and Nmic decreased with

  20. Optimum dose of 2-hydroxyethyl methacrylate based bonding material on pulp cells toxicity

    Directory of Open Access Journals (Sweden)

    Widya Saraswati


    Full Text Available Background: 2-hydroxyethyl methacrylate (HEMA, one type of resins commonly used as bonding base material, is commonly used due to its advantageous chemical characteristics. Several preliminary studies indicated that resin is a material capable to induce damage in dentin-pulp complex. It is necessary to perform further investigation related with its biological safety for hard and soft tissues in oral cavity. Purpose: The author performed an in vitro test to find optimum dose of HEMA resin monomer that may induce toxicity in pulp fibroblast cells. Method: The method of this study was experimental laboratory with post test control group design. Primary cell culture was made from dental pulp fibroblast cells, and was given with HEMA resin bonding material in various concentrations (5 µg/ml–2560 µg/ml, and then subjected to toxicity test (MTT assay. Result: HEMA optimum concentration was 320 µg/ml to induce cytotoxicity in pulp fibroblast cells. Conclusion: The used of HEMA - base bonding material with the concentration of 200 µg/ml may induced pulp fibroblas cell toxicity.Latar belakang: Keberhasilan suatu bahan bonding secara klinis tergantung pada kandungan fisik, kimia dan keamanan secara biologis. HEMA (2-hydroxyethyl methacrylate adalah bahan resin yang paling banyak digunakan karena memiliki sifat fisik-kimia yang baik. Beberapa penelitian pendahuluan menyebutkan bahwa resin merupakan bahan yang mampu menyebabkan gangguan pada kompleks dentin pulpa sehingga perlu dilakukan penelitian lebih lanjut menyangkut segi keamanan secara biologis bagi jaringan keras dan jaringan lunak di rongga mulut. Tujuan: Penelitian ini akan menguji secara in vitro (pada kultur sel fibroblas pulpa gigi untuk mengetahui dosis optimal monomer resin HEMA yang dapat menyebabkan toksisitas pada sel fibroblas pulpa. Metode: Metode penelitian ini adalah eksperimental laboratoris dengan rancangan penelitian post test control group design. Kultur sel primer dibuat dari

  1. Research on the image fusion and target extraction based on bionic compound eye system (United States)

    Zhang, Shaowei; Hao, Qun; Song, Yong; Wang, Zihan; Zhang, Kaiyu; Zhang, Shiyu


    People attach more and more importance to bionic compound eye due to its advantages such as small volume, large field of view and sensitivity to high-speed moving objects. Small field of view and large volume are the disadvantages of traditional image sensor and in order to avoid these defects, this paper intends to build a set of compound eye system based on insect compound eye structure and visual processing mechanism. In the center of this system is the primary sensor which has high resolution ratio. The primary sensor is surrounded by the other six sensors which have low resolution ratio. Based on this system, this paper will study the target image fusion and extraction method by using plane compound eye structure. This paper designs a control module which can combine the distinguishing features of high resolution image with local features of low resolution image so as to conduct target detection, recognition and location. Compared with traditional ways, the way of high resolution in the center and low resolution around makes this system own the advantages of high resolution and large field of view and enables the system to detect the object quickly and recognize the object accurately.

  2. Pyrimidine-based compounds modulate CXCR2-mediated signaling and receptor turnover. (United States)

    Ha, Helen; Neamati, Nouri


    Chemokine receptor CXCR2 is expressed on various immune cells and is essential for neutrophil recruitment and angiogenesis at sites of acute and chronic inflammation caused by tissue injury or infection. Because of its role in inflammation, it has been implicated in a number of immune-mediated inflammatory diseases such as psoriasis, arthritis, COPD, cystic fibrosis, asthma, and various types of cancer. CXCR2 and its ligands are up-regulated in cancer cells as well as the tumor microenvironment, promoting tumor growth, angiogenesis, and invasiveness. Although pharmaceutical companies have pursued the development of CXCR2-specific small-molecule inhibitors as anti-inflammatory agents within the last decades, there are currently no clinically approved CXCR2 inhibitors. Using a high-throughput, cell-based assay specific for CXCR2, we screened an in-house library of structurally diverse compounds and identified a class of pyrimidine-based compounds that alter CXCR2-mediated second messenger signaling. Our lead compound, CX797, inhibited IL8-mediated cAMP signaling and receptor degradation while specifically up-regulating IL8-mediated β-arrestin-2 recruitment. CX797 also inhibited IL8-mediated cell migration. Mechanistic comparison of CX797 and a previously reported CXCR2 inhibitor, SB265610, show these two classes of compounds have a distinct mechanism of action on CXCR2.

  3. Identification of compounds bound to suspended solids causing sub-lethal toxic effects in Daphnia magna. A field study on re-suspended particles during river floods in Ebro River. (United States)

    Rivetti, Claudia; Gómez-Canela, Cristian; Lacorte, Silvia; Díez, Sergi; Lázaro, Wilkinson L; Barata, Carlos


    Identifying chemicals causing adverse effects in organisms present in water remains a challenge in environmental risk assessment. This study aimed to assess and identify toxic compounds bound to suspended solids re-suspended during a prolonged period of flushing flows in the lower part of Ebro River (NE, Spain). This area is contaminated with high amounts of organochlorine and mercury sediment wastes. Chemical characterization of suspended material was performed by solid phase extraction using a battery of non-polar and polar solvents and analyzed by GC-MS/MS and LC-MS/MS. Mercury content was also determined for all sites. Post-exposure feeding rates of Daphnia magna were used to assess toxic effects of whole and filtered water samples and of re-constituted laboratory water with re-suspended solid fractions. Organochlorine and mercury residues in the water samples increased from upstream to downstream locations. Conversely, toxic effects were greater at the upstream site than downstream of the superfund Flix reservoir. A further analysis of the suspended solid fraction identified a toxic component eluted within the 80:20 methanol:water fraction. Characterization of that toxic component fraction by LC-MS/MS identified the phytotoxin anatoxin-a, whose residue levels were correlated with observed feeding inhibition responses. Further feeding inhibition assays conducted in the lab using anatoxin-a produced from Planktothrix agardhii, a filamentous cyanobacteria, confirmed field results. This study provides evidence that in real field situation measured contaminant residues do not always agree with toxic effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Evaluation of the Toxicity of 5-Aryl-2-Aminoimidazole-Based Biofilm Inhibitors against Eukaryotic Cell Lines, Bone Cells and the Nematode Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Hans Steenackers


    Full Text Available Previously, we have synthesized several series of compounds based on the 5-aryl-2-aminoimidazole scaffold, which showed a preventive activity against microbial biofilms. We here studied the cytotoxicity of the most active compounds of each series. First, the cytostatic activity was investigated against a number of tumor cell lines (L1210, CEM and HeLa. A subset of monosubstituted 5-aryl-2-aminoimidazoles showed a moderate safety window, with therapeutic indices (TIs ranging between 3 and 20. Whereas introduction of a (cyclo-alkyl chain at the N1-position strongly reduced the TI, introduction of a (cyclo-alkyl chain or a triazole moiety at the 2N-position increased the TI up to 370. Since a promising application of preventive anti-biofilm agents is their use in anti-biofilm coatings for orthopedic implants, their effects on cell viability and functional behavior of human osteoblasts and bone marrow derived mesenchymal stem cells were tested. The 2N-substituted 5-aryl-2-aminoimidazoles consistently showed the lowest toxicity and allowed survival of the bone cells for up to 4 weeks. Moreover they did not negatively affect the osteogenic differentiation potential of the bone cells. Finally, we examined the effect of the compounds on the survival of Caenorhabditis elegans, which confirmed the higher safety window of 2N-substituted 5-aryl-2-aminoimidazoles.

  5. Multi-view 3D echocardiography compounding based on feature consistency

    Energy Technology Data Exchange (ETDEWEB)

    Yao Cheng; Schaeffter, Tobias; Penney, Graeme P [Division of Imaging Sciences and Biomedical Engineering, King' s College London (United Kingdom); Simpson, John M, E-mail: [Department of Congenital Heart Disease, Evelina Children' s Hospital, London (United Kingdom)


    Echocardiography (echo) is a widely available method to obtain images of the heart; however, echo can suffer due to the presence of artefacts, high noise and a restricted field of view. One method to overcome these limitations is to use multiple images, using the 'best' parts from each image to produce a higher quality 'compounded' image. This paper describes our compounding algorithm which specifically aims to reduce the effect of echo artefacts as well as improving the signal-to-noise ratio, contrast and extending the field of view. Our method weights image information based on a local feature coherence/consistency between all the overlapping images. Validation has been carried out using phantom, volunteer and patient datasets consisting of up to ten multi-view 3D images. Multiple sets of phantom images were acquired, some directly from the phantom surface, and others by imaging through hard and soft tissue mimicking material to degrade the image quality. Our compounding method is compared to the original, uncompounded echocardiography images, and to two basic statistical compounding methods (mean and maximum). Results show that our method is able to take a set of ten images, degraded by soft and hard tissue artefacts, and produce a compounded image of equivalent quality to images acquired directly from the phantom. Our method on phantom, volunteer and patient data achieves almost the same signal-to-noise improvement as the mean method, while simultaneously almost achieving the same contrast improvement as the maximum method. We show a statistically significant improvement in image quality by using an increased number of images (ten compared to five), and visual inspection studies by three clinicians showed very strong preference for our compounded volumes in terms of overall high image quality, large field of view, high endocardial border definition and low cavity noise.


    Institute of Scientific and Technical Information of China (English)

    银燕; 张倩; 贾兴真; 张聿为


    目的:观察一种葡萄糖酸氯己定复方消毒液的杀菌效果与毒性。方法采用悬液定量杀菌试验和动物毒性试验方法,对该葡萄糖酸氯己定复方消毒液相关性能进行了实验室观察。结果该复方消毒液原液含葡萄糖酸氯己定4840 mg/L、乙醇含量为体积分数40%。以该复方消毒液原液对悬液内金黄色葡萄球菌、大肠杆菌、铜绿假单胞菌作用1.0 min,平均杀灭对数值均﹥5.00;对白色念珠菌杀灭对数值﹥4.00。用该消毒液原液擦拭消毒1.0 min,对手和前臂皮肤上自然菌的杀灭对数值均﹥1.00。该复方消毒液对小鼠急性经口毒性LD50值﹥5000 mg/kg(体重),对家兔皮肤无刺激性;1000~5000 mg/kg(体重)剂量范围,该复方消毒液对小鼠骨髓嗜多染红细胞微核试验结果为阴性。结论该葡萄糖酸氯己定复方消毒液对细菌繁殖体和真菌杀菌效果良好,属实际无毒级物质,无致突变作用,对皮肤无刺激性。%Objective To observe the germicidal effect and toxicity of the chlorhexidine gluconate compound disinfect-ant. Methods The suspension quantitative germicidal test and animal toxicity test were used to observe the related effi-ciency of the chlorhexidine gluconate compound disinfectant in lab. Results This compound disinfectant contained chlo-rhexidine gluconate 4 840 mg/L and the ethanol 40%( v/v). The average killing logarithm values of Staphylococcus au-reus,Escherichia coli and Pseudomonas aeruginosa exposed to the chlorhexidine gluconate compound disinfectant for 1. 0 min were all above 5. 00 while that of Candida albicans was above 4. 00. The killing logarithm value of the natural bac-teria on the skin of hand and forearm was above 1. 00 while wiping with the compound disinfectant for 1 min. The LD50 of the mouse acute oral toxicity with the compound disinfectant was 5 000 mg/kg·bw,and this disinfectant had no skin irrita-tion to rabbit. The result of

  7. A category approach to predicting the developmental (neuro) toxicity of organotin compounds: The value of the zebrafish (Danio rerio) embryotoxicity test (ZET)

    NARCIS (Netherlands)

    Beker van Woudenberg, A.; Wolterbeek, A.; Brake, L. te; Snel, C.; Menke, A.; Rubingh, C.; Groot, D. de; Kroese, D.


    Zebrafish embryos were exposed to different organotin compounds during very early development (<100. h post fertilization). Morphology, histopathology and swimming activity (in a motor activity test) were the endpoints analyzed. DBTC was, by far, the most embryotoxic compound at all time points and

  8. A QSPR model for estimation of lower flammability limit temperature of pure compounds based on molecular structure. (United States)

    Gharagheizi, Farhad


    In this study, a quantitative structure-property relationship was presented to estimate lower flammability limit temperature (LFLT) of pure compounds. This relationship is a multi-linear equation and has six parameters. These chemical structure-based parameters were selected from 1664 molecular-based parameters by genetic algorithm multivariate linear regression (GA-MLR). Since 1171 compounds were used to develop this equation, the model can be used to estimate the LFLT of a wide range of pure compounds.

  9. BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds. (United States)

    Hongthong, Khwanjira; Ratanaphan, Adisorn


    Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). The clinicopathological characteristics of TNBC include a high grading, a high rate of cell proliferation and a greater degree of chromosomal rearrangement. Patients with triple-negative breast cancer are more likely to be drug resistant and more difficult to treat, and are also frequently BRCA1 mutants. Methylation of the BRCA1 promoter region is associated with a reduction of the BRCA1 mRNA level. TNBC patients with a methylated BRCA1 had a better disease-free survival compared with those with non-methylated BRCA1. From a therapeutic perspective, the expression level of BRCA1 has been a major determinant of the responses to different classes of chemotherapy. BRCA1-dysfunctional tumors are hypersensitive to DNA damaging chemotherapeutic agents like platinum drugs. Although platinum based drugs are currently widely used as conventional chemotherapeutic drugs in breast cancer chemotherapy, their use has several disadvantages. It is therefore of interest to seek out alternative therapeutic metal-based compounds that could overcome the limitations of these platinum based drugs. Ruthenium-based compounds could be the most promising alternative to the platinum drugs. This review highlights the use of BRCA1 as a predictive marker as well as for a potential drug target for anticancer ruthenium compounds.

  10. Toxic myopathies. (United States)

    Pasnoor, Mamatha; Barohn, Richard J; Dimachkie, Mazen M


    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, because they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features, and possible underlying cellular mechanisms.

  11. A DFT-based toxicity QSAR study of aromatic hydrocarbons to Vibrio fischeri: Consideration of aqueous freely dissolved concentration. (United States)

    Wang, Ying; Yang, Xianhai; Wang, Juying; Cong, Yi; Mu, Jingli; Jin, Fei


    In the present study, quantitative structure-activity relationship (QSAR) techniques based on toxicity mechanism and density functional theory (DFT) descriptors were adopted to develop predictive models for the toxicity of alkylated and parent aromatic hydrocarbons to Vibrio fischeri. The acute toxicity data of 17 aromatic hydrocarbons from both literature and our experimental results were used to construct QSAR models by partial least squares (PLS) analysis. With consideration of the toxicity process, the partition of aromatic hydrocarbons between water phase and lipid phase and their interaction with the target biomolecule, the optimal QSAR model was obtained by introducing aqueous freely dissolved concentration. The high statistical values of R(2) (0.956) and Q(CUM)(2) (0.942) indicated that the model has good goodness-of-fit, robustness and internal predictive power. The average molecular polarizability (α) and several selected thermodynamic parameters reflecting the intermolecular interactions played important roles in the partition of aromatic hydrocarbons between the water phase and biomembrane. Energy of the highest occupied molecular orbital (E(HOMO)) was the most influential descriptor which dominated the toxicity of aromatic hydrocarbons through the electron-transfer reaction with biomolecules. The results demonstrated that the adoption of freely dissolved concentration instead of nominal concentration was a beneficial attempt for toxicity QSAR modeling of hydrophobic organic chemicals.

  12. Standard Test Method for Preparing Aircraft Cleaning Compounds, Liquid Type, Water Base, for Storage Stability Testing

    CERN Document Server

    American Society for Testing and Materials. Philadelphia


    1.1 This test method covers the determination of the stability in storage, of liquid, water-base chemical cleaning compounds, used to clean the exterior surfaces of aircraft. 1.2 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.

  13. O-methylation of natural phenolic compounds based on green chemistry using dimethyl carbonate (United States)

    Prakoso, N. I.; Pangestu, P. H.; Wahyuningsih, T. D.


    The alkyl aryl ether compounds, of which methyl eugenol and veratraldehyde are the simplest intermediates can be synthesized by reacting eugenol and vanillin with the green reagent dimethyl carbonate (DMC). The reaction was carried out under mild of temperature and pressure. Excellent yields and selective products were obtained (95-96%) after a few hours. In the end of the reaction, the catalysts (base and Phase Transfer Catalyst) can be recovered and regenerated.

  14. Strength and durability of concrete modified by sulfur-based impregnating compounds


    MASSALIMOV Ismail Alexandrovich; YANAKHMETOV Marat Rafisovich; CHUYKIN Alexander Eugenyevich


    The aim of the research was to determine how sulfur-containing compound impregnation influences on concrete compressive strength and the impact resistance of concrete tiles. The results of these studies indicate that impregnation of vibropressed concrete paving tiles and concrete samples of dif-ferent strength classes with aqueous solutions based on calcium polysulfide leads to a significant increase of compressive strength and impact resistance. These data show that the strength of the pr...

  15. A Compound Fuzzy Disturbance Observer Based on Sliding Modes and Its Application on Flight Simulator


    Yunjie Wu; Youmin Liu; Dapeng Tian


    A compound fuzzy disturbance observer based on sliding modes is developed, and its application on flight simulator is presented. Fuzzy disturbance observer (FDO) is an effective method in nonlinear control. However, traditional FDO is confined to monitor dynamic disturbance, and the frequency bandwidth of the system is restricted. Sliding mode control (SMC) compensates the high-frequency component of disturbance while it is limited by the chattering phenomenon. The proposed method uses the sl...

  16. Determining anti-betanodavirus compounds through a GF-1 cell-based screening platform. (United States)

    Huang, Yi-Cheng; Han, Yu-San


    Betanodavirus is a highly contagious pathogen, responsible for severe losses incurred in the aquaculture industry. Currently, there are no commercially available antivirals against the virulence observed during very early stages of fish larvae development. Therefore, we developed a novel GF-1 (grouper fin cell) cell viability-based screening assay to facilitate the discovery of an anti-betanodavirus agent. The assay conditions were optimized and the robustness of the assay was confirmed by a Z' factor value ranging from 0.7 to 0.94. After screening a library of 2000 small molecule compounds, 43 compounds with a virus inhibition capacity of ⩾55% were identified. A cytochrome P450 inhibitor, proadifen hydrochloride, was validated with an EC50 value of 6.48μM and a CC50 value of 20.63μM. This compound inhibited the amplification of viral RNA by 99.68% 5days post-infection. Surprisingly, we found that 18 of 43 compounds act as neurotransmitter agents. These findings indicate a novel way of investigating the infection mechanism of betanodavirus, and suggest potential candidates for an anti-betanodavirus drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Highly Stereoselective Synthesis of a Compound Collection Based on the Bicyclic Scaffolds of Natural Products. (United States)

    Annamalai, Murali; Hristeva, Stanimira; Bielska, Martyna; Ortega, Raquel; Kumar, Kamal


    Despite the great contribution of natural products in the history of successful drug discovery, there are significant limitations that persuade the pharmaceutical industry to evade natural products in drug discovery research. The extreme scarcity as well as structural complexity of natural products renders their practical synthetic access and further modifications extremely challenging. Although other alternative technologies, particularly combinatorial chemistry, were embraced by the pharmaceutical industry to get quick access to a large number of small molecules with simple frameworks that often lack three-dimensional complexity, hardly any success was achieved in the discovery of lead molecules. To acquire chemotypes beholding structural features of natural products, for instance high sp³ character, the synthesis of compound collections based on core-scaffolds of natural products presents a promising strategy. Here, we report a natural product inspired synthesis of six different chemotypes and their derivatives for drug discovery research. These bicyclic hetero- and carbocyclic scaffolds are highly novel, rich in sp³ features and with ideal physicochemical properties to display drug likeness. The functional groups on the scaffolds were exploited further to generate corresponding compound collections. Synthesis of two of these collections exemplified with ca. 350 compounds are each also presented. The whole compound library is being exposed to various biological screenings within the European Lead Factory consortium.

  18. Bionic Mosaic Method of Panoramic Image Based on Compound Eye of Fly

    Institute of Scientific and Technical Information of China (English)

    Haipeng Chen; Xuanjing Shen; Xiaofei Li; Yushan Jin


    To satisfy the requirements of real-time and high quality mosaics,a bionic compound eye visual system was designed by simulating the visual mechanism of a fly compound eye.Several CCD cameras were used in this system to imitate the small eyes of a compound eye.Based on the optical analysis of this system,a direct panoramic image mosaic algorithm was proposed.Several sub-images were collected by the bionic compound eye visual system,and then the system obtained the overlapping proportions of these sub-images and cut the overlap sections of the neighboring images.Thus,a panoramic image with a large field of view was directly mosaicked,which expanded the field and guaranteed the high resolution.The experimental results show that the time consumed by the direct mosaic algorithm is only 2.2% of that by the traditional image mosaic algorithm while guaranteeing mosaic quality.Furthermore,the proposed method effectively solved the problem of misalignment of the mosaic image and eliminated mosaic cracks as a result of the illumination factor and other factors.This method has better real-time properties compared to other methods.

  19. QSAR based docking studies of marine algal anticancer compounds as inhibitors of protein kinase B (PKBβ). (United States)

    Davis, G Dicky John; Vasanthi, A Hannah Rachel


    Marine algae are prolific source of bioactive secondary metabolites and are found to be active against different cancer cell lines. QSAR studies will explicate the significance of a particular class of descriptor in eliciting anticancer activity against a cancer type. Marine algal compounds showing anticancer activity against six different cancer cell lines namely MCF-7, A431, HeLa, HT-29, P388 and A549 taken from Seaweed metabolite database were subjected to comprehensive QSAR modeling studies. A hybrid-GA (genetic algorithm) optimization technique for descriptor space reduction and multiple linear regression analysis (MLR) approach was used as fitness functions. Cell lines HeLa and MCF-7 showed good statistical quality (R(2)∼0.75, Q(2)∼0.65) followed by A431, HT29 and P388 cell lines with reasonable statistical values (R(2)∼0.70, Q(2)∼0.60). The models developed were interpretable, with good statistical and predictive significance. Molecular descriptor analyses revealed that Baumann's alignment-independent topological descriptors had a major role in variation of activity along with other descriptors. Incidentally, earlier QSAR analysis on a variety of chemically diverse PKBα inhibitors revealed Baumann's alignment-independent topological descriptors that differentiated the molecules binding to Protein kinase B (PKBα) kinase or PH domain, hence a docking study of two crystal structures of PKBβ was performed for identification of novel ATP-competitive inhibitors of PKBβ. Five compounds had a good docking score and Callophycin A showed better ligand efficiency than other PKBβ inhibitors. Furthermore in silico pharmacokinetic and toxicity studies also showed that Callophycin A had a high drug score (0.85) compared to the other inhibitors. These results encourages discovering novel inhibitors for cancer therapeutic targets by screening metabolites from marine algae.

  20. Carbon Nanomaterials Based Electrochemical Sensors/Biosensors for the Sensitive Detection of Pharmaceutical and Biological Compounds

    Directory of Open Access Journals (Sweden)

    Bal-Ram Adhikari


    Full Text Available Electrochemical sensors and biosensors have attracted considerable attention for the sensitive detection of a variety of biological and pharmaceutical compounds. Since the discovery of carbon-based nanomaterials, including carbon nanotubes, C60 and graphene, they have garnered tremendous interest for their potential in the design of high-performance electrochemical sensor platforms due to their exceptional thermal, mechanical, electronic, and catalytic properties. Carbon nanomaterial-based electrochemical sensors have been employed for the detection of various analytes with rapid electron transfer kinetics. This feature article focuses on the recent design and use of carbon nanomaterials, primarily single-walled carbon nanotubes (SWCNTs, reduced graphene oxide (rGO, SWCNTs-rGO, Au nanoparticle-rGO nanocomposites, and buckypaper as sensing materials for the electrochemical detection of some representative biological and pharmaceutical compounds such as methylglyoxal, acetaminophen, valacyclovir, β-nicotinamide adenine dinucleotide hydrate (NADH, and glucose. Furthermore, the electrochemical performance of SWCNTs, rGO, and SWCNT-rGO for the detection of acetaminophen and valacyclovir was comparatively studied, revealing that SWCNT-rGO nanocomposites possess excellent electrocatalytic activity in comparison to individual SWCNT and rGO platforms. The sensitive, reliable and rapid analysis of critical disease biomarkers and globally emerging pharmaceutical compounds at carbon nanomaterials based electrochemical sensor platforms may enable an extensive range of applications in preemptive medical diagnostics.

  1. 1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats

    Directory of Open Access Journals (Sweden)

    Atul Rawat


    Full Text Available Introduction: Erythromycin (ERY is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group: control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a decreased TCA cycle activity and enhanced fatty acid oxidation, (b dysfunction of lipid and amino acid metabolism and (c oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new

  2. Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, H. [Sungkyunkwan Univ., Seoul (Korea, Republic of). Dept. of Health Sciences and Technology; Oh, D.; Park, H.C.; Han, Y.; Lim, D.H. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of). Dept. of Radiation Oncology; Kang, S.W. [Korea Univ., Seoul (Korea, Republic of). Dept. of Radiologic Science; Paik, S.W. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of). Dept. of Medicine


    Purpose: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT). Patients and methods: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the {>=} grade 2 GD toxicity were investigated. Results: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V{sub 25} for stomach and V{sub 35} for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for {>=} grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V{sub 25} {<=} 6.3 % and 57.1 % for V{sub 25} > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V{sub 35} > 5.4 % and 45.9 % for V{sub 35} > 5.4 %. By multivariate analysis including the clinical factors, V{sub 25} for stomach and V{sub 35} for duodenum were the significant factors. Conclusion: EGD revealed that GD toxicity is common following RT for HCC. V{sub 25} for the stomach and V{sub 35} for the duodenum were the significant factors to predict {>=} grade 2 GD toxicity. (orig.)

  3. Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals

    DEFF Research Database (Denmark)

    Rendal, Cecilie; Kusk, Kresten Ole; Trapp, Stefan


    It is recognized that the pH of exposure solutions can influence the toxicity and bioaccumulation of ionizing compounds. The present study investigates whether it can be considered a general rule that an ionizable compound is more toxic and more bioaccumulative when in the neutral state. Three...... processes were identified to explain the behavior of ionizing compounds with changing pH: the change in lipophilicity when a neutral compound becomes ionized, electrical attraction, and the ion trap. The literature was screened for bioaccumulation and toxicity tests of ionizing organic compounds performed...... a dynamic flux model based on the Fick-Nernst-Planck diffusion equation known as the cell model. The cell model predicts that bases with delocalized charges may in some cases show declining bioaccumulation with increasing pH. Little information is available for amphoteric and zwitterionic compounds; however...

  4. Hypermethylation of the DPYD promoter region is not a major predictor of severe toxicity in 5-fluorouracil based chemotherapy

    Directory of Open Access Journals (Sweden)

    Aebi Stefan


    Full Text Available Abstract Background The activity of dihydropyrimidine dehydrogenase (DPD, the key enzyme of pyrimidine catabolism, is thought to be an important determinant for the occurrence of severe toxic reactions to 5-fluorouracil (5-FU, which is one of the most commonly prescribed chemotherapeutic agents for the treatment of solid cancers. Genetic variation in the DPD gene (DPYD has been proposed as a main factor for variation in DPD activity in the population. However, only a small proportion of severe toxicities in 5-FU based chemotherapy can be explained with such rare deleterious DPYD mutations resulting in severe enzyme deficiencies. Recently, hypermethylation of the DPYD promoter region has been proposed as an alternative mechanism for DPD deficiency and thus as a major cause of severe 5-FU toxicity. Methods Here, the prognostic significance of this epigenetic marker with respect to severe 5-FU toxicity was assessed in 27 cancer patients receiving 5-FU based chemotherapy, including 17 patients experiencing severe toxic side effects following drug administration, none of which were carriers of a known deleterious DPYD mutation, and ten control patients. The methylation status of the DPYD promoter region in peripheral blood mononuclear cells was evaluated by analysing for each patient between 19 and 30 different clones of a PCR-amplified 209 base pair fragment of the bisulfite-modified DPYD promoter region. The fragments were sequenced to detect bisulfite-induced, methylation-dependent sequence differences. Results No evidence of DPYD promoter methylation was observed in any of the investigated patient samples, whereas in a control experiment, as little as 10% methylated genomic DNA could be detected. Conclusion Our results indicate that DYPD promoter hypermethylation is not of major importance as a prognostic factor for severe toxicity in 5-FU based chemotherapy.

  5. Standardization of Tragopogon graminifolius DC. Extract Based on Phenolic Compounds and Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Mohammad Hosein Farzaei


    Full Text Available Tragopogon graminifolius DC. (TG, Compositae family, is traditionally used for the treatment of various diseases like gastrointestinal and hepatic disorders. The aim of the present study is to standardize extracts from TG used for preparation of different dosage forms in traditional Iranian medicine (TIM based on phenolic compounds. For this purpose, total phenolic content and some phenolic compounds were determined in ethanolic extracts from aerial part and root of TG by HPLC method. Furthermore, antioxidant activity was evaluated using DPPH-HPLC methods. Caffeic acid, gallic acid, ρ-coumaric acid, ferulic acid, and catechin were detected in root and aerial part of TG. ρ-Coumaric acid (6.357 ± 0.014 mg·g−1 was dominant phenolic compound in aerial part followed by ferulic acid (1.24 ± 0.018 mg·g−1. Also, ρ-coumaric acid (2.685 ± 0.031 mg·g−1 was highly abundant in root, followed by catechin (2.067 ± 0.021 mg·g−1. Antioxidant activity of root extract (460.45 ± 0.78 µg Vit.E.E·mL−1 was better than that of aerial part. Generally, phenolic compounds are one of the major constituents of TG and could be used as markers for standardization of dosage forms prepared from this plant. Also, TG demonstrated significant antioxidant activity using DPPH-HPLC method. Phenolic compounds of TG may be responsible for its marked antioxidant properties.

  6. Syntheses, Crystal Structures and Fluorescent Properties of Two New Imidazolidino Schiff Base Compounds

    Institute of Scientific and Technical Information of China (English)

    FENG Yue; LIU Gang; TIAN Xiu-Mei; WANG Ji-De; WANG Wei


    Two new imidazolidino Schiff base compounds, (E)-N-((quinoxalin-2-yl)methylene)-2-(2-(quinoxalin-3-yl)imidazolidin-1-yl)ethanamine 1 and 2-(1-(2-(2-(quinoxalin-3-yl)imidazolidin-1-yl)ethyl)imidazolidin-2-yl)quinoxaline 2, have been synthesized and characterized by elemental analysis,1H NMR, IR, MS and single-crystal X-ray diffraction. Crystallographic data for 1: C22H21N7,Mr = 383.46, monoclinic, space group P21, a = 7.0036(14), b=6.9151(14), c=19.701(4)(A),β=96.57(3)°, Z = 2, V=947.9(3)(A)3, Dc = 1.344 g/cm3, F(000)=404, μ = 0.085 mm-1, Flack parameter =0(2), R = 0.0464 and wR = 0.1055; and those for 2: C24H26N8, Mr = 426.53, triclinic, space group P(1),a = 9.6680(19), b = 10.334(2), c = 11.389(2)(A),α= 104.12(3),β= 102.95(3),γ= 100.48(3)°, Z=2,V=1041.2(4)(A)3, Dc=1.361 g/cm3, F(000) = 452,μ = 0.086 mm-1, R = 0.0373 and wR = 0.1155. For the two compounds, the five-membered imidazolidine rings all adopt envelope conformation.Moreover, the title compounds show one-dimensional layered and three-dimensional supramolecular chainlike structures, respectively. Fluorescent properties of the two compounds have been investigated in the solid state at room temperature. Compound 1 exhibits strong fluorescence and thus may serve as excellent candidates of green fluorescent materials.

  7. Evaluation of toxicity to the biological treatment and removal of recalcitrant organic compounds from oil refineries wastewaters; Avaliacao da toxicidade ao tratamento biologico e remocao de compostos organicos recalcitrantes existentes em efluentes de refinarias de petroleo

    Energy Technology Data Exchange (ETDEWEB)

    Barros Junior, Laerte M.; Macedo, Gorete R.; Bezerra, Marcio S.; Pereira, Franklin M.S. [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Engenharia Quimica; Schmidell, Willibaldo [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil)


    Oil industry waste water usually contains recalcitrant chemical compounds, like phenol, benzene, toluene, xylene, naphthalene and acenaphthene. The respirometry, determination of respiration rate of an active biomass, is an adequate methodology for quantification of aerobic activity biological. This study aims evaluate the inhibition effect of phenol in the oxidation capacity of an industrial sludge. This work also intends to study the phenol removal through biological and photochemical-biological processes. The respirometry was carried out with synthetic solution, using sludge from an oil processing industry. The phenol degradation experiments were carried out in an activated sludge unit and in a photochemical reactor. This work suggests the potential of photochemical-biological treatment use, in relation to the biological process with a no-acclimated sludge, in the removal of refractory organic compounds from oil industry wastewaters. The characterization of biomass using the respirometry methodology showed which is a useful tool in evaluation of phenol toxicity to biological treatment. (author)

  8. In vitro evaluation of candidate pretreatment and treatment compounds against sulfur mustard (HD) -induced human mononuclear leukocyte toxicity using a dye exclusion cell viability assay

    Energy Technology Data Exchange (ETDEWEB)

    Starner, R.A.; Blank, J.A.; Hobson, D.W.; Menton, R.G.; Meier, H.L.


    An assay measuring propidium iodide (PI) incorporation into nonviable human peripheral blood mononuclear leukocytes (PBML) was established at the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD), and the technology transferred and implemented at Battelle's Medical Research and Evaluation Facility (MREF) for use as a screen to evaluate candidate compounds for direct cytotoxicity as well as for efficacy in preventing HD-induced cytotoxicity. For assay transition, studies were performed to establish a fixed HD challenge concentration; to develop a positive and negative control dataset; and to establish the reproducibility in obtaining an EC50 (concentration of candidate compound required to provide 50 percent protection against the fixed HD concentration) for niacinamide (NM). Various concentrations of candidate compounds were preincubated for 15 to 30 min with PBML prior to adding the fixed HD challenge. At 24 hr after exposure, PI was added to the cultures and the number of nonviable (PI positive) cells was determined by flow cytometry. Positive (NM pretreated) and negative (HD only) controls were examined concurrently and used to maintain data quality. From this dataset, candidate compounds were evaluated for direct cytotoxic effects and for efficacy in preventing HD-induced cytotoxicity. EC50 values for effective candidate compounds were estimated and reported for ranking compound effectiveness. Results from these studies demonstrate assay function and reproducibility during routine screening operations.

  9. Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae. (United States)

    Mániková, Dominika; Vlasáková, Danusa; Loduhová, Jana; Letavayová, Lucia; Vigasová, Dana; Krascsenitsová, Eva; Vlcková, Viera; Brozmanová, Jela; Chovanec, Miroslav


    Selenium (Se) belongs to nutrients that are essential for human health. Biological activity of this compound, however, mainly depends on its dose, with a potential of Se to induce detrimental effects at high doses. Although mechanisms lying behind detrimental effects of Se are poorly understood yet, they involve DNA damage induction. Consequently, DNA damage response and repair pathways may play a crucial role in cellular response to Se. Using Saccharomyces cerevisiae we showed that sodium selenite (SeL), an inorganic form of Se, can be toxic and mutagenic in this organism due to its ability to induce DNA double-strand breaks (DSBs). Moreover, we reported that a spectrum of mutations induced by this compound in the stationary phase of growth is mainly represented by 1-4 bp deletions. Consequently, we proposed that SeL acts as an oxidizing agent in yeast producing oxidative damage to DNA. As short deletions could be anticipated to arise as a result of action of non-homologous end-joining (NHEJ) and oxidative damage to DNA is primarily coped with base excision repair (BER), a contribution of these two pathways towards survival, DSB induction, mutation frequency and types of mutations following SeL exposure was examined in present study. First, we show that while NHEJ plays no role in repairing toxic DNA lesions induced by SeL, cells with impairment in BER are sensitized towards this compound. Of BER activities examined, those responsible for processing of 3'-blocking DNA termini seem to be the most crucial for manifestation of the toxic effects of SeL in yeast. Second, an impact of NHEJ and BER on DSB induction after SeL exposure turned to be inappreciable, as no increase in DNA double-strand breakage in NHEJ and BER single or NHEJ BER double mutant upon SeL exposure was observed. Finally, we demonstrate that impairment in both these pathways does not importantly change mutation frequency after SeL exposure and that NHEJ is not responsible for generation of short

  10. Toxicity tests based on predator-prey and competitive interactions between freshwater macroinvertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, E.J.; Blockwell, S.J.; Pascoe, D. [Univ. of Wales Coll. of Cardiff (United Kingdom)


    Simple multi-species toxicity tests based on the predation of Daphnia magna Straus by Hydra oligactis (Pallas) and competition between Gammarus pulex (L.) and Asellus aquaticus (L.) were used to determine the effects of three reference chemicals. Criteria examined included functional responses; time to first captures; handling times (predator/prey systems) and co-existence and growth. The tests which proved most practicable and sensitive (lowest observed effects 0.1, 21, and 80 {micro}g/l for lindane, copper and 3,4 dichloroaniline, respectively) were: (1) predator-prey tests: determining changes in the size-structure of predated D. magna populations and (2) competition tests: measuring the feeding rate of G. pulex competing with A. aquaticus, using a bioassay based on the time-response analysis of the consumption of Artemia salina eggs. The concentration of a chemical which affected particular response criteria was fond to depend on the test system employed. Results of the tests indicated that effects were often not dose-related and that a given criterion could be variously affected by different test concentrations. The complex pattern of responses may be explained in terms of the differential sensitivity of the interacting species and perhaps subtle alteration in strategies. The sensitivity of the bioassay endpoints is compared to those of a range of single species tests, and their value for predicting the impact pollutants may have upon natural freshwater ecosystems is discussed.

  11. Syntheses, magnetic and spectral studies on polystyrene supported coordination compounds of bidentate and tetradentate Schiff bases

    Indian Academy of Sciences (India)

    D Kumar; P K Gupta; A Syamal


    The reaction of aminomethylated polystyrene (PSCH2-NH2) and 2-hydroxyacetanilide in DMF results in the formation of polystyrene-anchored monobasic bidentate Schiff base, PSCH2-LH (I). On the other hand, the reaction of chloromethylated polystyrene (PSCH2-Cl), 3-formylsalicylic acid, ethylenediamine and acetylacetone in DMF in presence of ethyl acetate (EA) and triethylamine (TEA) produces another polystyrene-anchored dibasic tetradentate Schiff base, PSCH2-L'H2 (II). Both I and II react with a number of di-, tri- and hexavalent metal ions like Co, Ni, Cu, Zn and Cd to form polystyreneanchored coordination compounds, and these have been characterized and discussed.

  12. Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays (United States)

    de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra


    Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

  13. High temperature thermal diffusivity of nickel-based superalloys and intermetallic compounds


    Hazotte, A.; Perrot, B.; Archambault, P


    By means of an installation developed in our laboratory, we measured the thermal diffusivity (α) as a function of temperature for several single and polycrystal nickel-based superalloys as well as for different intermetallic compounds with a L12 (Ni3Al, Ni3Si, Ni3Ge, Ni3Fe, Zr3Al, Co3Ti), L10 (TiAl) or B2 (NiAl) structure. In the case of nickel-based superalloys, the experiments pointed out an unexpected but reproductible slope change in the α=f(T) curves at about 750°C, which is not explaine...

  14. Green chromatography separation of analytes of greatly differing properties using a polyethylene glycol stationary phase and a low-toxic water-based mobile phase. (United States)

    Šatínský, Dalibor; Brabcová, Ivana; Maroušková, Alena; Chocholouš, Petr; Solich, Petr


    A simple, rapid, and environmentally friendly HPLC method was developed and validated for the separation of four compounds (4-aminophenol, caffeine, paracetamol, and propyphenazone) with different chemical properties. A "green" mobile phase, employing water as the major eluent, was proposed and applied to the separation of analytes with different polarity on polyethylene glycol (PEG) stationary phase. The chromatography separation of all compounds and internal standard benzoic acid was performed using isocratic elution with a low-toxicity mobile phase consisting of 0.04% (v/v) triethylamine and water. HPLC separation was carried out using a PEG reversed-phase stationary phase Supelco Discovery HS PEG column (15 × 4 mm; particle size 3 μm) at a temperature of 30 °C and flow rate at 1.0 mL min(-1). The UV detector was set at 210 nm. In this study, a PEG stationary phase was shown to be suitable for the efficient isocratic separation of compounds that differ widely in hydrophobicity and acid-base properties, particularly 4-aminophenol (log P, 0.30), caffeine (log P, -0.25), and propyphenazone (log P, 2.27). A polar PEG stationary phase provided specific selectivity which allowed traditional chromatographic problems related to the separation of analytes with different polarities to be solved. The retention properties of the group of structurally similar substances (aromatic amines, phenolic compounds, and xanthine derivatives) were tested with different mobile phases. The proposed green chromatography method was successfully applied to the analysis of active substances and one degradation impurity (4-aminophenol) in commercial preparation. Under the optimum chromatographic conditions, standard calibration was carried out with good linearity correlation coefficients for all compounds in the range (0.99914-0.99997, n = 6) between the peak areas and concentration of compounds. Recovery of the sample preparation was in the range 100 ± 5% for all compounds

  15. Filter based receive-side spatial compounding for veterinary ultrasound B-mode imaging. (United States)

    Liu, Wen; Cheng, Yangjie; Liu, Dong C


    Veterinary ultrasound has been used in a large number of animal husbandry-related circumstances while many corresponding applications also call for the use of ultrasound in human patients. However, veterinary ultrasound images are affected by speckle, an interference pattern that can reduce the quality and contrast of ultrasound images. In this paper, a filter-based receive-side spatial compounding technique for veterinary ultrasound B-Mode imaging is used to create a compounded veterinary B-Mode image based on multiple looks. In particular, filtering in the lateral direction has been proved to be able to preserve the axial information in the sub-bands and to create decorrelation between sub-bands at the expense of some lateral resolution. A new method was proposed to obtain B-Mode IQ data by special veterinary ultrasonic probe. This approach is tested on 275 in-vivo swine. The effect is accomplished in real-time veterinary ultrasonic imaging with a measurable improvement of SNRe. Meanwhile, the speckle and electronic noise in the compounded image have been greatly reduced and smoothed in the visual result.

  16. A design and application of compound multi-functional sensor in wood-based panel processing

    Institute of Scientific and Technical Information of China (English)

    XU Kai-hong; ZHOU Ding-guo


    A compound multi-functional sensor was designed by the study on the on-line testing technology of wood-based panels, and its properties of shape, functions, size, resistance to special environment were studied in details. The operational principles of different sensors, technical flow of manufacturing, development of software systems of special functions, and the assessments of technical specification were also be introduced. This sensor adopted many new technologies, such as the applications of piezoresistant effect and heat sensitive effect can effectively measure the pressure and temperature, digital signal processing technology was used to extract and treat signals, and resist interference, encapsulation technology was used to keep the normal run of sensor under a harsh environment. Thus, the on-line compound multi-functional temperature/pressure sensor can be applied better to supervise the production of wood-based panels. All technical specifications of the compound multi-functional sensor were tested and the results met the requirements of the equipments.

  17. Leaching characteristics of calcium-based compounds in MSWI Residues: From the viewpoint of clogging risk. (United States)

    Xia, Yi; Zhang, Hua; Phoungthong, Khamphe; Shi, Dong-Xiao; Shen, Wen-Hui; Shao, Li-Ming; He, Pin-Jing


    Leachate collection system (LCS) clogging caused by calcium precipitation would be disadvantageous to landfill stability and operation. Meanwhile, calcium-based compounds are the main constituents in both municipal solid waste incineration bottom ash (MSWIBA) and stabilized air pollution control residues (SAPCR), which would increase the risk of LCS clogging once these calcium-rich residues were disposed in landfills. The leaching behaviors of calcium from the four compounds and municipal solid waste incineration (MSWI) residues were studied, and the influencing factors on leaching were discussed. The results showed that pH was the crucial factor in the calcium leaching process. CaCO3 and CaSiO3 began leaching when the leachate pH decreased to less than 7 and 10, respectively, while Ca3(PO4)2 leached at pHCaSiO3>Ca3(PO4)2>CaCO3. The calcium leaching from the MSWIBA and SAPCR separately started from pH<7 and pH<12, resulting from CaCO3 and Ca3(PO4)2 leaching respectively, which was proven by the X-ray diffraction results. Based on the leaching characteristics of the different calcium compounds and the mineral phase of calcium in the incineration residues, simulated computation of their clogging potential was conducted, providing the theoretical basis for the risk assessment pertaining to LCS clogging in landfills. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Synthesis of new 1,2,4-triazole compounds containing Schiff and Mannich bases (morpholine) with antioxidant and antimicrobial activities. (United States)

    Ünver, Yasemin; Deniz, Sadik; Çelik, Fatih; Akar, Zeynep; Küçük, Murat; Sancak, Kemal


    Compound 2 was synthesized by reacting CS2/KOH with compound 1. The treatment of compound 2 with hydrazine hydrate produced compound 3. Then, compound 3 was converted to Schiff bases (4a-d) by the handling with several aromatic aldehydes. The treatment of triazole compounds 4a-d containing Schiff base with morpholine gave compounds 5a-d. All compounds were tested for their antioxidant and antimicrobial activities. The antioxidant test results of DPPH• radical scavenging and ferric reducing/antioxidant power methods showed good antioxidant activity. The triazole-thiol (3) was the most active, and the effect of the substituent type of the thiophene ring on the activity was same for both Schiff bases (4a-d) and Mannich bases (5a-d). Among the newly synthesized triazole derivatives, the Schiff base 4d and the Mannich base 5d carrying nitro substituent on the thiophene ring showed promising antibacterial and antifungal activity, with lower MIC values than the standard antibacterial ampicillin.

  19. Mars atmospheric entry guidance for reference trajectory tracking based on robust nonlinear compound controller (United States)

    Dai, Juan; Gao, Ai; Xia, Yuanqing


    A robust entry guidance law based on terminal sliding mode and second-order differentiator is designed for trajectory tracking in this paper. The bank angle is regarded as the control variable. A novel nonlinear compound controller is designed to make the system with the trajectory-tracking error and its rate as states be input-to-state stable (ISS) with respect to uncertainties. The terminal sliding mode controller is designed to the problem of entry guidance by using the second-order differentiator to estimate the total disturbances. The proposed nonlinear compound control law by employing the second-order differentiator and the terminal sliding mode controller, provide robustness, higher control precision. Also, simulation results are presented to illustrate the effectiveness of the control strategy.

  20. Comparative study of laterite and bentonite based organoclays: implications of hydrophobic compounds remediation from aqueous solutions. (United States)

    Nafees, Muhammad; Waseem, Amir; Khan, Abdur Rehman


    Four cost effective organoclays were synthesized, characterized, and studied for the sorption of hydrophobic compounds (edible oil/grease and hydrocarbon oil) from aqueous solutions. Organoclays were prepared by cation exchange reaction of lattice ions (present onto the surface of laterite and bentonite clay minerals) with two surfactants, hexadecyl trimethyl ammonium chloride (HDTMA-Cl) and tetradecyl trimethyl ammonium bromide (TDTMA-Br). Fourier transform infrared spectroscopy and scanning electron microscopy were used for the characterization of synthesized organoclays. It was found that the amount of surfactant loading and the nature of the surfactant molecules used in the syntheses of organoclay strongly affect the sorption capacity of the clay mineral. Further, it was found that both the laterite and bentonite based organoclays efficiently removed the edible and hydrocarbon oil content from lab prepared emulsions; however, the adsorption capacity of clay mineral was greatly influenced by the nature of hydrophobic compounds as well.


    Directory of Open Access Journals (Sweden)

    S. Ebenezer Juliet


    Full Text Available This paper presents a one pass block classification algorithm for efficient coding of compound images which consists of multimedia elements like text, graphics and natural images. The objective is to minimize the loss of visual quality of text during compression by separating text information which needs high special resolution than the pictures and background. It segments computer screen images into text/graphics and picture/background classes based on DCT energy in each 4x4 block, and then compresses both text/graphics pixels and picture/background blocks by H.264/AVC with variable quantization parameter. Experimental results show that the single H.264/AVC-INTRA coder with variable quantization outperforms single coders such as JPEG, JPEG-2000 for compound images. Also the proposed method improves the PSNR value significantly than standard JPEG, JPEG-2000 and while keeping competitive compression ratios.

  2. Comparative Study of Laterite and Bentonite Based Organoclays: Implications of Hydrophobic Compounds Remediation from Aqueous Solutions

    Directory of Open Access Journals (Sweden)

    Muhammad Nafees


    Full Text Available Four cost effective organoclays were synthesized, characterized, and studied for the sorption of hydrophobic compounds (edible oil/grease and hydrocarbon oil from aqueous solutions. Organoclays were prepared by cation exchange reaction of lattice ions (present onto the surface of laterite and bentonite clay minerals with two surfactants, hexadecyl trimethyl ammonium chloride (HDTMA-Cl and tetradecyl trimethyl ammonium bromide (TDTMA-Br. Fourier transform infrared spectroscopy and scanning electron microscopy were used for the characterization of synthesized organoclays. It was found that the amount of surfactant loading and the nature of the surfactant molecules used in the syntheses of organoclay strongly affect the sorption capacity of the clay mineral. Further, it was found that both the laterite and bentonite based organoclays efficiently removed the edible and hydrocarbon oil content from lab prepared emulsions; however, the adsorption capacity of clay mineral was greatly influenced by the nature of hydrophobic compounds as well.

  3. Toxicity of iron-based nanoparticles to green algae: Effects of particle size, crystal phase, oxidation state and environmental aging. (United States)

    Lei, Cheng; Zhang, Luqing; Yang, Kun; Zhu, Lizhong; Lin, Daohui


    With the increasing environmental application and discharge of iron-based nanoparticles (NPs), a comprehensive understanding of their fate and ecotoxicological effect in the aquatic environment is very urgent. In this study, toxicities of 4 zero-valent iron NPs (nZVI) of different sizes, 2 Fe2O3 NPs of different crystal phases, and 1 type of Fe3O4 NPs to a green alga (Chlorella pyrenoidosa) were investigated, with a focus on the effects of particle size, crystal phase, oxidation state, and environmental aging. Results show that the algal growth inhibition of nZVI increased significantly with decreasing particle size; with similar particle sizes (20-30 nm), the algal growth inhibition decreased with oxidation of the NPs with an order of nZVI > Fe3O4 NPs > Fe2O3 NPs, and α-Fe2O3 NPs presented significantly higher toxicity than γ-Fe2O3 NPs. The NP-induced oxidative stress was the main toxic mechanism, which could explain the difference in algal toxicity of the NPs. The NP-cell heteroagglomeration and physical interactions also contributed to the nanotoxicity, whereas the effect of NP dissolution was negligible. The aging in distilled water and 3 surface water samples for 3 months increased surface oxidation of the iron-based NPs especially nZVI, which decreased the toxicity to algae. These findings will be helpful for the understanding of the fate and toxicity of iron-based NPs in the aquatic environment.

  4. Leaching characteristics of calcium-based compounds in MSWI Residues: From the viewpoint of clogging risk

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Yi [State Key Laboratory of Pollution Control & Resource Reuse, Tongji University, Shanghai 200092 (China); Institute of Waste Treatment and Reclamation, Tongji University, Shanghai 200092 (China); Zhang, Hua, E-mail: [State Key Laboratory of Pollution Control & Resource Reuse, Tongji University, Shanghai 200092 (China); Phoungthong, Khamphe [State Key Laboratory of Pollution Control & Resource Reuse, Tongji University, Shanghai 200092 (China); Institute of Waste Treatment and Reclamation, Tongji University, Shanghai 200092 (China); Shi, Dong-Xiao; Shen, Wen-Hui [Changzhou Domestic Waste Treatment Center, Changzhou 213000 (China); Shao, Li-Ming [Institute of Waste Treatment and Reclamation, Tongji University, Shanghai 200092 (China); Center for the Technology Research and Training on Household Waste in Small Towns & Rural Area, Ministry of Housing and Urban–Rural Development of PR China (MOHURD), Shanghai 200092 (China); He, Pin-Jing, E-mail: [Institute of Waste Treatment and Reclamation, Tongji University, Shanghai 200092 (China); Center for the Technology Research and Training on Household Waste in Small Towns & Rural Area, Ministry of Housing and Urban–Rural Development of PR China (MOHURD), Shanghai 200092 (China)


    Highlights: • The leaching behavior of Ca-based compounds commonly in MSWI residues was studied. • pH is the crucial factor for calcium leaching process. • CaCO{sub 3} was the most sensitive to leaching temperature and Ca{sub 3}(PO{sub 4}){sub 2} was the least. • Ca leaching of MSWIBA and SAPCR attributed to CaCO{sub 3} and Ca{sub 3}(PO{sub 4}){sub 2} respectively. • Potential clogging ability of MSWI residues leachate in open air was calculated. - Abstract: Leachate collection system (LCS) clogging caused by calcium precipitation would be disadvantageous to landfill stability and operation. Meanwhile, calcium-based compounds are the main constituents in both municipal solid waste incineration bottom ash (MSWIBA) and stabilized air pollution control residues (SAPCR), which would increase the risk of LCS clogging once these calcium-rich residues were disposed in landfills. The leaching behaviors of calcium from the four compounds and municipal solid waste incineration (MSWI) residues were studied, and the influencing factors on leaching were discussed. The results showed that pH was the crucial factor in the calcium leaching process. CaCO{sub 3} and CaSiO{sub 3} began leaching when the leachate pH decreased to less than 7 and 10, respectively, while Ca{sub 3}(PO{sub 4}){sub 2} leached at pH < 12. CaSO{sub 4} could hardly dissolve in the experimental conditions. Moreover, the sequence of the leaching rate for the different calcium-based compounds is as follows: CaSiO{sub 3} > Ca{sub 3}(PO{sub 4}){sub 2} > CaCO{sub 3}. The calcium leaching from the MSWIBA and SAPCR separately started from pH < 7 and pH < 12, resulting from CaCO{sub 3} and Ca{sub 3}(PO{sub 4}){sub 2} leaching respectively, which was proven by the X-ray diffraction results. Based on the leaching characteristics of the different calcium compounds and the mineral phase of calcium in the incineration residues, simulated computation of their clogging potential was conducted, providing the

  5. Potent antifouling compounds produced by marine Streptomyces

    KAUST Repository

    Xu, Ying


    Biofouling causes huge economic loss and a recent global ban on organotin compounds as antifouling agents has increased the need for safe and effective antifouling compounds. Five structurally similar compounds were isolated from the crude extract of a marine Streptomyces strain obtained from deep-sea sediments. Antifouling activities of these five compounds and four other structurally-related compounds isolated from a North Sea Streptomyces strain against major fouling organisms were compared to probe structure-activity relationships of compounds. The functional moiety responsible for antifouling activity lies in the 2-furanone ring and that the lipophilicity of compounds substantially affects their antifouling activities. Based on these findings, a compound with a straight alkyl side-chain was synthesized and proved itself as a very effective non-toxic, anti-larval settlement agent against three major fouling organisms. The strong antifouling activity, relatively low toxicity, and simple structures of these compounds make them promising candidates for new antifouling additives. © 2009 Elsevier Ltd. All rights reserved.

  6. Computer based screening of compound databases: 1. Preselection of benzamidine-based thrombin inhibitors. (United States)

    Fox, T; Haaksma, E E


    We present a computational protocol which uses the known three-dimensional structure of a target enzyme to identify possible ligands from databases of compounds with low molecular weight. This is accomplished by first mapping the essential interactions in the binding site with the program GRID. The resulting regions of favorable interaction between target and ligand are translated into a database query, and with UNITY a flexible 3D database search is performed. The feasibility of this approach is calibrated with thrombin as the target. Our results show that the resulting hit lists are enriched with thrombin inhibitors compared to the total database.

  7. Lead toxicity thresholds in 17 Chinese soils based on substrate-induced nitrification assay. (United States)

    Li, Ji; Huang, Yizong; Hu, Ying; Jin, Shulan; Bao, Qiongli; Wang, Fei; Xiang, Meng; Xie, Huiting


    The influence of soil properties on toxicity threshold values for Pb toward soil microbial processes is poorly recognized. The impact of leaching on the Pb threshold has not been assessed systematically. Lead toxicity was screened in 17 Chinese soils using a substrate-induced nitrification (SIN) assay under both leached and unleached conditions. The effective concentration of added Pb causing 50% inhibition (EC50) ranged from 185 to >2515mg/kg soil for leached soil and 130 to >2490mg/kg soil for unleached soil. These results represented >13- and >19-fold variations among leached and unleached soils, respectively. Leaching significantly reduced Pb toxicity for 70% of both alkaline and acidic soils tested, with an average leaching factor of 3.0. Soil pH and CEC were the two most useful predictors of Pb toxicity in soils, explaining over 90% of variance in the unleached EC50 value. The relationships established in the present study predicted Pb toxicity within a factor of two of measured values. These relationships between Pb toxicity and soil properties could be used to establish site-specific guidance on Pb toxicity thresholds.

  8. An environmentally friendly method to remove and utilize the highly toxic strychnine in other products based on proton-transfer complexation (United States)

    Adam, Abdel Majid A.; Refat, Moamen S.; Saad, Hosam A.; Hegab, Mohamed S.


    The study of toxic and carcinogenic substances represents one of the most demanding areas in human safety, due to their repercussions for public health. There is great motivation to remove and utilize these substances in other products instead of leaving them contaminate the environment. One potentially toxic compound for humans is strychnine (Sy). In the present study, we attempted to establish a quick, simple, direct and efficient method to remove and utilize discarded Sy in other products based on proton-transfer complexation. First, Sy was reacted with the acido organic acceptors PA, DNBA and CLA. Then, the resultant salts were direct carbonized into carbon materials. Also, this study provides an insight into the structure and morphology of the obtained products by a range of physicochemical techniques, such as UV-visible, IR, 1H NMR and 13C NMR spectroscopies; XRD; SEM; TEM; and elemental and thermal analyses. Interestingly, the complexation of Sy with the PA or DNBA acceptor leads to a porous carbon material, while its complexation with CLA acceptor forms non-porous carbon product.

  9. Study on mutagenic and toxic compounds in lake water used as drinking water supply; Ricerca di sostanze mutagene e tossiche in acque lacustri destinate a scopo potabile

    Energy Technology Data Exchange (ETDEWEB)

    Monarca, S.; Zanardini, A. [Brescia Univ. (Italy). Fac. di Medicina e Chirurgia, Cattedra di Igiene e Odontoiatria Preventiva; Dalmiglio, A. [USL 15, U.O. Fisica e Tutela dell`Ambiente, PMIP, Darfo (Italy); Feretti, D.; Nardi, G. [Brescia Univ. (Italy). Fac. di Medicina e Chirurgia, cattedra di Igiene; Benfenati, E. [Istituto di Ricerche Farmacologiche `Mario Negri`, Milan (Italy)


    Trace amounts of mutagenic and toxic substances are frequently found in drinking water, causing a great concern for their potential health effects. Aim of this work is to develop a reliable and efficient screening method for detecting aquatic mutagens and toxins in surface water used for human consumption. For this purpose different methods of concentration of lake water have been experimented by using three different solid phase extraction systems at different pHs and studying the adsorbates by means of a mutagenicity test (Ames test), a toxicity test (LUMIStox) and chemical analysis (GC,MS). This integrated chemical/biological approach showed to be a suitable system for the preliminary choice of an efficient screening method for aquatic mutagens and toxins and to give useful data for the evaluation of potential health hazards.

  10. Evaluation of Selected Subacute Effects of the Nitrotoluene Group of Munitions Compounds on Fish and Potential Use in Aquatic Toxicity Evaluation. (United States)


    most cases. It is not possible to distinguish an anterior and posterior region in the juvenile bluegill. Spermatozoa are not usually present in the...Seminiferous tubules with spermatozoa (a) filling the lumen of each Vf I tubule. Note numerous mitotic figures in the L epithelium of the tubules. F...198 Cardwell, R.D., Foreman, D.G., Payne, T.R. and Wilber, D.J., "Acute toxicity of selenium dioxide to fresh water fishes", Arch. Envir. Contam

  11. Study on material base and action mechanism of compound Danshen dripping pills for treatment of atherosclerosis based on modularity analysis. (United States)

    Zhou, Wei; Yuan, Wen-Feng; Chen, Chao; Wang, Shu-Mei; Liang, Sheng-Wang


    Traditional Chinese medicine (TCM) has been widely used in China and its surrounding countries in clinical treatments for centuries-long time. However, due to the complexity of TCM constituents, both action mechanism and material base of TCM remain nearly unknown. The present study was designed to uncover the action mechanism and material base of TCM in a low-cost manner. Compound Danshen dripping pills (DSP) is a widely used TCM for treatment of atherosclerosis, and was researched here to demonstrate the effectiveness of our method. We constructed a heterogeneous network for DSP, identified the significant network module, and analyzed the primary pharmacological units by performing GO and pathways enrichment analysis. Two significant network modules were identified from the heterogeneous network of DSP, and three compounds out of four hub nodes in the network were found to intervene in the process of atherosclerosis. Moreover, 13 out of 20 enriched pathways that were ranked in top 10 corresponding to both the two pharmacological units were found to be involved in the process of atherosclerosis. Quercetin, luteolin and apigenin may be the main active compounds which modulate the signaling pathways, such as metabolism of xenobiotics by cytochrome P450, retinol metabolism, etc. The present method helps reveal the action mechanism and material base of DSP for treatment of atherosclerosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila


    Shieh, Shin-Yi; Bonini, Nancy M.


    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the ...

  13. Identification of sublethal toxicants in a BC coastal pulp and paper mill effluent

    Energy Technology Data Exchange (ETDEWEB)

    Eickhoff, C.V.; Pickard, J.; Kinnee, K. [BC Research Inc., Vancouver, BC (Canada); Dwernychuk, W. [Hatfield Consultants Ltd., West Vancouver, BC (Canada); Birkholz, D. [EnviroTest Lab., Edmonton, AB (Canada); Kilback, D. [Pacifica Papers, Powell River, BC (Canada)


    BC Research Inc. conducted a toxicity identification evaluation to identify the different compounds comprised in the mill Outfall number 1 effluent. The Environmental Effects Monitoring program had determined that these compounds were responsible for sublethal effects to organisms. Echinoderm species like the sand dollar, Dendraster excentricus Eshscholtz, the purple sea urchin, Stronglyocentrotus purpuratus Stimpson, and the marine algae, Champia parvula had suffered toxicity caused by the mill effluent. The last several Environmental Effects Monitoring testing periods had shown the sublethal toxicity of the Outfall number 1 effluent to echinoderms was very consistent. Based on the high cost and shipping associated with the Champia bioassays, toxicity tests conducted during the peak spawning season of the sea urchin and the non significant difference between the sensitivity of the sand dollar and the purple sea urchin, the purple sea urchin was selected to evaluate the toxicity of the manipulated samples for the tests. The tests conducted were: a baseline toxicity test performed immediately upon receipt of the effluent sample, the pH adjustment filtration test to determine if the toxic compound can be removed using filtration, the pH adjustment aeration test to determine if volatile compounds in the sample are toxic, the pH adjustment solid phase extraction test to determine the level of toxicity from organic compounds and metal chelates that can be removed by solid phase extraction. The results indicated that it seems high molecular weight molecules were responsible for the sublethal toxicity observed. Two different sources could be responsible: lignin derived macromolecules, and polymer compounds used as flocculants and sizing agents. Further testing of the pulp mill effluent to identify the source of the toxic high molecular weight compounds was recommended. 22 refs., 4 tabs., 6 figs.

  14. Biology-based modeling to analyze uranium toxicity data on Daphnia magna in a multigeneration study. (United States)

    Massarin, Sandrine; Beaudouin, Remy; Zeman, Florence; Floriani, Magali; Gilbin, Rodolphe; Alonzo, Frederic; Pery, Alexandre R R


    Recent studies have investigated chronic toxicity of waterborne depleted uranium on the life cycle and physiology of Daphnia magna. In particular, a reduction in food assimilation was observed. Our aims here were to examine whether this reduction could fully account for observed effects on both growth and reproduction, for three successive generations, and to investigate through microscope analyses whether this reduction resulted from direct damage to the intestinal epithelium. We analyzed data obtained by exposing Daphnia magna to uranium over three successive generations. We used energy-based models, which are both able to fit simultaneously growth and reproduction and are biologically relevant. Two possible modes of action were compared - decrease in food assimilation rate and increase in maintenance costs. In our models, effects were related either to internal concentration or to exposure concentration. The model that fitted the data best represented a decrease in food assimilation related to exposure concentration. Furthermore, observations of consequent histological damage to the intestinal epithelium, together with uranium precipitates in the epithelial cells, supported the assumption that uranium has direct effects on the digestive tract. We were able to model the data in all generations and showed that sensitivity increased from one generation to the next, in particular through a significant increase of the intensity of effect, once the threshold for appearance of effects was exceeded.

  15. An estuarine mudsnail in situ toxicity assay based on postexposure feeding. (United States)

    Krell, Bonny; Moreira-Santos, Matilde; Ribeiro, Rui


    In situ assays provide more realistic exposure scenarios than laboratory assays, which is particularly pertinent for estuaries because exposure conditions are difficult to simulate. Traditionally, sublethal toxicity testing endpoints, such as growth, emergence, and reproduction, imply time-delayed extrapolations from individuals to populations, communities, and ecosystems. Sublethal responses mechanistically linked to ecosystem functions have been largely neglected. Feeding is an unequivocal ecologically meaningful response because its impairment has direct and immediate effects on ecosystems, by hampering key functions such as organic matter decomposition, long before its effects at the individual level have consequences at successively higher levels of biological organization. The ultimate goal of the present study was to widen the range of ecosystem functions for estuarine quality assessments. Specifically, a short-term in situ assay based on the postexposure feeding of the mudsnail Hydrobia ulvae is presented. Methodologies to quantify precisely postexposure egestion as a surrogate of feeding were achieved. A multiple regression model from laboratory experiments was successfully applied to an in situ assay at reference (Mira River) and contaminated Portuguese estuaries (Sado River) for predicting reference results and allowing unraveling confounding factors during exposure (temperature, salinity, sediment grain size). Sensitivity comparisons of postexposure feeding with survival and growth, after Cu exposure, were carried out and used for a first preliminary appraisal of the relative consequences of ecosystem-level immediate effects. Copyright © 2011 SETAC.

  16. Thioglycolate-based task-specific ionic liquids: Metal extraction abilities vs acute algal toxicity. (United States)

    Platzer, Sonja; Leyma, Raphlin; Wolske, Sara; Kandioller, Wolfgang; Heid, Esther; Schröder, Christian; Schagerl, Michael; Krachler, Regina; Jirsa, Franz; Keppler, Bernhard K


    We studied the extraction behavior of two thioglycolate-based ionic liquids (ILs), for heavy metals from aqueous solutions; substances of interest were methyltrioctylammonium S-hexyl thioglycolate [N1888][C6SAc] and methyltrioctylphosphonium S-hexyl thioglycolate [P1888][C6SAc]. Theses ILs previously have shown very good extraction abilities towards cadmium and copper, therefore we investigated time-dependent metal removal experiments with aqueous solutions of cobalt(II), nickel(II) and zinc(II). The highest distribution ratio (RIL/Water) was determined for zinc (RIL/Water=2000). Recovery studies for zinc after extraction were performed with different stripping agents showing a successful recycling. Additionally, the two ILs were immobilized on active charcoal, displaying great potential for solid-liquid extraction. Regarding the extraction mechanism, quantum-mechanical calculations were included, which indicate that the metal extraction depends on the stability of the metal-water cluster. Ligands (water as well as ILs) are planar coordinated in nickel complexes but showed a tetrahedral configuration for zinc. As a first estimate of the ecotoxicity of the ILs, in vivo tests toward three freshwater green algae species Tetradesmus obliquus, Desmodesmus armatus and Raphidocelis subcapitata were carried out. The EC50 values (effective concentration after 72 h) confirm high toxicity of all tested ILs to all species, displaying only small differences between the species and EC50ies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  17. The association of bacterial C9-based TTX-like compounds with Prorocentrum minimum opens new uncertainties about shellfish seafood safety (United States)

    Rodríguez, Inés; Alfonso, Amparo; Alonso, Eva; Rubiolo, Juan A.; Roel, María; Vlamis, Aristidis; Katikou, Panagiota; Jackson, Stephen A.; Menon, Margassery Lekha; Dobson, Alan; Botana, Luis M.


    In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum minimum (P. minimum) in Greece. The connexion between TTX and P. minimum was further studied in this paper. First, the presence of TTX-producer bacteria, Vibrio and Pseudomonas spp, was confirmed in Greek mussels. In addition these samples showed high activity as inhibitors of sodium currents (INa). P. minimum was before associated with neurotoxic symptoms, however, the nature and structure of toxins produced by this dinoflagellate remains unknown. Three P. minimum strains, ccmp1529, ccmp2811 and ccmp2956, growing in different conditions of temperature, salinity and light were used to study the production of toxic compounds. Electrophysiological assays showed no effect of ccmp2811 strain on INa, while ccmp1529 and ccmp2956 strains were able to significantly reduce INa in the same way as TTX. In these samples two new compounds, m/z 265 and m/z 308, were identified and characterized by liquid chromatography tandem high-resolution mass spectrometry. Besi