Effects-driven chemical fractionation of heavy fuel oil to isolate compounds toxic to trout embryos.

Science.gov (United States)

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

2014-04-01

Heavy fuel oil (HFO) spills account for approximately 60% of ship-source oil spills and are up to 50 times more toxic than medium and light crude oils. Heavy fuel oils contain elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and alkyl-PAHs, known to be toxic to fish; however, little direct characterization of HFO toxicity has been reported. An effects-driven chemical fractionation was conducted on HFO 7102 to separate compounds with similar chemical and physical properties, including toxicity, to isolate the groups of compounds most toxic to trout embryos. After each separation, toxicity tests directed the next phase of fractionation, and gas chromatography-mass spectrometry analysis correlated composition with toxicity, with a focus on PAHs. Low-temperature vacuum distillation permitted the separation of HFO into 3 fractions based on boiling point ranges. The most toxic of these fractions underwent wax precipitation to remove long-chain n-alkanes. The remaining PAH-rich extract was further separated using open column chromatography, which provided distinct fractions that were grouped according to increasing aromatic ring count. The most toxic of these fractions was richest in PAHs and alkyl-PAHs. The results of the present study were consistent with previous crude oil studies that identified PAH-rich fractions as the most toxic. © 2013 SETAC.

Chemopreventive effect of natural dietary compounds on xenobiotic-induced toxicity

Directory of Open Access Journals (Sweden)

Jia-Ching Wu

2017-01-01

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.

Toxic effects on and structure-toxicity relationships of phenylpropanoids, terpenes, and related compounds in Aedes aegypti larvae.

Science.gov (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

2010-12-01

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.

Toxic pollutants emitted from thermal decomposition of phthalimide compounds

Energy Technology Data Exchange (ETDEWEB)

Chen Kai; Mackie, John C.; Wojtalewicz, Dominika; Kennedy, Eric M. [Process Safety and Environmental Protection Research Group, School of Engineering, The University of Newcastle, Callaghan, New South Wales 2308 (Australia); Dlugogorski, Bogdan Z., E-mail: Bogdan.Dlugogorski@newcastle.edu.au [Process Safety and Environmental Protection Research Group, School of Engineering, University of Newcastle, Callaghan, New South Wales 2308 (Australia)

2011-03-15

Phthalimide (PI) and tetrahydrophthalimide (THPI) are two structurally similar compounds extensively used as intermediates for the synthesis of variety of industrial chemicals. This paper investigates the thermal decomposition of PI and THPI under oxygen rich to oxygen lean conditions, quantifying the production of toxicants and explaining their formation pathways. The experiments involved a plug flow reactor followed by silica cartridges, activated charcoal trap and a condenser, with the decomposition products identified and quantified by Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS) and micro gas chromatography ({mu}GC). The density functional theory (DFT) calculations served to obtain dissociation energies and reaction pathways, to elucidate the reaction mechanism. The oxidation of PI and THPI produced several toxic nitrogen-containing gases and volatile organic compounds, including hydrogen cyanide, isocyanic acid, nitrogen oxides, benzonitrile, maleimide and tentatively identified benzenemethanimine. The detection of dibenzo-p-dioxin (DD) and dibenzofuran (DF) suggests potential formation of the toxic persistent organic pollutants (POPs) in fires involving PI and THPI, in presence of a chlorine source. The oxidation of THPI produced 2-cyclohexen-1-one, a toxic unsaturated ketone. The results of the present study provide the data for quantitative risk assessments of emissions of toxicants in combustion processes involving PI and THPI.

Toxic pollutants emitted from thermal decomposition of phthalimide compounds

International Nuclear Information System (INIS)

Chen Kai; Mackie, John C.; Wojtalewicz, Dominika; Kennedy, Eric M.; Dlugogorski, Bogdan Z.

2011-01-01

Phthalimide (PI) and tetrahydrophthalimide (THPI) are two structurally similar compounds extensively used as intermediates for the synthesis of variety of industrial chemicals. This paper investigates the thermal decomposition of PI and THPI under oxygen rich to oxygen lean conditions, quantifying the production of toxicants and explaining their formation pathways. The experiments involved a plug flow reactor followed by silica cartridges, activated charcoal trap and a condenser, with the decomposition products identified and quantified by Fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS) and micro gas chromatography (μGC). The density functional theory (DFT) calculations served to obtain dissociation energies and reaction pathways, to elucidate the reaction mechanism. The oxidation of PI and THPI produced several toxic nitrogen-containing gases and volatile organic compounds, including hydrogen cyanide, isocyanic acid, nitrogen oxides, benzonitrile, maleimide and tentatively identified benzenemethanimine. The detection of dibenzo-p-dioxin (DD) and dibenzofuran (DF) suggests potential formation of the toxic persistent organic pollutants (POPs) in fires involving PI and THPI, in presence of a chlorine source. The oxidation of THPI produced 2-cyclohexen-1-one, a toxic unsaturated ketone. The results of the present study provide the data for quantitative risk assessments of emissions of toxicants in combustion processes involving PI and THPI.

Accurate prediction of the toxicity of benzoic acid compounds in mice via oral without using any computer codes

International Nuclear Information System (INIS)

Keshavarz, Mohammad Hossein; Gharagheizi, Farhad; Shokrolahi, Arash; Zakinejad, Sajjad

2012-01-01

Highlights: ► A novel method is introduced for desk calculation of toxicity of benzoic acid derivatives. ► There is no need to use QSAR and QSTR methods, which are based on computer codes. ► The predicted results of 58 compounds are more reliable than those predicted by QSTR method. ► The present method gives good predictions for further 324 benzoic acid compounds. - Abstract: Most of benzoic acid derivatives are toxic, which may cause serious public health and environmental problems. Two novel simple and reliable models are introduced for desk calculations of the toxicity of benzoic acid compounds in mice via oral LD 50 with more reliance on their answers as one could attach to the more complex outputs. They require only elemental composition and molecular fragments without using any computer codes. The first model is based on only the number of carbon and hydrogen atoms, which can be improved by several molecular fragments in the second model. For 57 benzoic compounds, where the computed results of quantitative structure–toxicity relationship (QSTR) were recently reported, the predicted results of two simple models of present method are more reliable than QSTR computations. The present simple method is also tested with further 324 benzoic acid compounds including complex molecular structures, which confirm good forecasting ability of the second model.

Assessment of multi-chemical pollution in aquatic ecosystems using toxic units: compound prioritization, mixture characterization and relationships with biological descriptors.

Science.gov (United States)

Ginebreda, Antoni; Kuzmanovic, Maja; Guasch, Helena; de Alda, Miren López; López-Doval, Julio C; Muñoz, Isabel; Ricart, Marta; Romaní, Anna M; Sabater, Sergi; Barceló, Damià

2014-01-15

Chemical pollution is typically characterized by exposure to multiple rather than to single or a limited number of compounds. Parent compounds, transformation products and other non-targeted compounds yield mixtures whose composition can only be partially identified by monitoring, while a substantial proportion remains unknown. In this context, risk assessment based on the application of additive ecotoxicity models, such as concentration addition (CA), is rendered somewhat misleading. Here, we show that ecotoxicity risk information can be better understood upon consideration of the probabilistic distribution of risk among the different compounds. Toxic units of the compounds identified in a sample fit a lognormal probability distribution. The parameters characterizing this distribution (mean and standard deviation) provide information which can be tentatively interpreted as a measure of the toxic load and its apportionment among the constituents in the mixture (here interpreted as mixture complexity). Furthermore, they provide information for compound prioritization tailored to each site and enable prediction of some of the functional and structural biological variables associated with the receiving ecosystem. The proposed approach was tested in the Llobregat River basin (NE Spain) using exposure and toxicity data (algae and Daphnia) corresponding to 29 pharmaceuticals and 22 pesticides, and 5 structural and functional biological descriptors related to benthic macroinvertebrates (diversity, biomass) and biofilm metrics (diatom quality, chlorophyll-a content and photosynthetic capacity). Aggregated toxic units based on Daphnia and algae bioassays provided a good indication of the pollution pattern of the Llobregat River basin. Relative contribution of pesticides and pharmaceuticals to total toxic load was variable and highly site dependent, the latter group tending to increase its contribution in urban areas. Contaminated sites' toxic load was typically dominated by

Comparison of the toxicity of fluoridation compounds in the nematode Caenorhabditis elegans.

Science.gov (United States)

Rice, Julie R; Boyd, Windy A; Chandra, Dave; Smith, Marjolein V; Den Besten, Pamela K; Freedman, Jonathan H

2014-01-01

Fluorides are commonly added to drinking water in the United States to decrease the incidence of dental caries. Silicofluorides, such as sodium hexafluorosilicate (Na2 SiF6 ) and fluorosilicic acid (H2 SiF6 ), are mainly used for fluoridation, although fluoride salts such as sodium fluoride (NaF) are also used. Interestingly, only the toxicity of NaF has been examined and not that of the more often used silicofluorides. In the present study, the toxicities of NaF, Na2 SiF6 , and H2 SiF6 were compared. The toxicity of these fluorides on the growth, feeding, and reproduction in the alternative toxicological testing organism Caenorhabditis elegans was examined. Exposure to these compounds produced classic concentration-response toxicity profiles. Although the effects of the fluoride compounds varied among the 3 biological endpoints, no differences were found between the 3 compounds, relative to the fluoride ion concentration, in any of the assays. This suggests that silicofluorides have similar toxicity to NaF. © 2013 SETAC.

The chemical nature of phenolic compounds determines their toxicity and induces distinct physiological responses in Saccharomyces cerevisiae in lignocellulose hydrolysates

Science.gov (United States)

2014-01-01

We investigated the severity of the inhibitory effects of 13 phenolic compounds usually found in spruce hydrolysates (4-hydroxy-3-methoxycinnamaldehyde, homovanilyl alcohol, vanillin, syringic acid, vanillic acid, gallic acid, dihydroferulic acid, p-coumaric acid, hydroquinone, ferulic acid, homovanillic acid, 4-hydroxybenzoic acid and vanillylidenacetone). The effects of the selected compounds on cell growth, biomass yield and ethanol yield were studied and the toxic concentration threshold was defined for each compound. Using Ethanol Red, the popular industrial strain of Saccharomyces cerevisiae, we found the most toxic compound to be 4-hydroxy-3-methoxycinnamaldehyde which inhibited growth at a concentration of 1.8 mM. We also observed that toxicity did not generally follow a trend based on the aldehyde, acid, ketone or alcohol classification of phenolic compounds, but rather that other structural properties such as additional functional groups attached to the compound may determine its toxicity. Three distinctive growth patterns that effectively clustered all the compounds involved in the screening into three categories. We suggest that the compounds have different cellular targets, and that. We suggest that the compounds have different cellular targets and inhibitory mechanisms in the cells, also compounds who share similar pattern on cell growth may have similar inhibitory effect and mechanisms of inhibition. PMID:24949277

Comparison of Toxicities to Vibrio fischeri and Fish Based on Discrimination of Excess Toxicity from Baseline Level

Science.gov (United States)

Wang, Xiao H.; Yu, Yang; Huang, Tao; Qin, Wei C.; Su, Li M.; Zhao, Yuan H.

2016-01-01

Investigations on the relationship of toxicities between species play an important role in the understanding of toxic mechanisms to environmental organisms. In this paper, the toxicity data of 949 chemicals to fish and 1470 chemicals to V. fischeri were used to investigate the modes of action (MOAs) between species. The results show that although there is a positive interspecies correlation, the relationship is poor. Analysis on the excess toxicity calculated from toxic ratios (TR) shows that many chemicals have close toxicities and share the same MOAs between the two species. Linear relationships between the toxicities and octanol/water partition coefficient (log KOW) for baseline and less inert compounds indicate that the internal critical concentrations (CBRs) approach a constant both to fish and V. fischeri for neutral hydrophobic compounds. These compounds share the same toxic mechanisms and bio-uptake processes between species. On the other hand, some hydrophilic compounds exhibit different toxic effects with greatly different log TR values between V. fischeri and fish species. These hydrophilic compounds were identified as reactive MOAs to V. fischeri, but not to fish. The interspecies correlation is improved by adding a hydrophobic descriptor into the correlation equation. This indicates that the differences in the toxic ratios between fish and V. fischeri for these hydrophilic compounds can be partly attributed to the differences of bioconcentration between the two species, rather than the differences of reactivity with the target macromolecules. These hydrophilic compounds may more easily pass through the cell membrane of V. fischeri than the gill and skin of fish, react with the target macromolecules and exhibit excess toxicity. The compounds with log KOW > 7 exhibiting very low toxicity (log TR toxicity and MOAs. PMID:26901437

Toxicity of essential oil compounds against Exorista sorbillans ...

African Journals Online (AJOL)

Essential oils of Ageratum conyzoides and Ocimum species are potential candidates for management of Exorista sorbillans (Wiedemann) (Diptera: Culicidae), a serious pest of silkworm. Considering that the pure compounds in essential oil may exhibit efficacy against the parasitoid, contact and topical toxicity of 22 essential ...

Toxic organic compounds from energy production

Energy Technology Data Exchange (ETDEWEB)

Hites, R.A.

1991-09-20

The US Department of Energy's Office of Health and Environmental Research (OHER) has supported work in our laboratory since 1977. The general theme of this program has been the identification of potentially toxic organic compounds associated with various combustion effluents, following the fates of these compounds in the environment, and improving the analytical methodology for making these measurements. The projects currently investigation include: an improved sampler for semi-volatile compounds in the atmosphere; the wet and dry deposition of dioxins and furans from the atmosphere; the photodegradation and mobile sources of dioxins and furans; and the bioaccumulation of PAH by tree bark. These projects are all responsive to OHER's interest in the pathways and mechanisms by which energy-related agents move through and are modified by the atmosphere''. The projects on gas chromatographic and liquid chromatographic tandem mass spectrometry are both responsive to OHER's interest in new and more sensitive technologies for chemical measurements''. 35 refs., 9 figs.

Photocatalytic Degradation of 4-Nitrophenol by C, N-TiO2: Degradation Efficiency vs. Embryonic Toxicity of the Resulting Compounds

Science.gov (United States)

Osin, Oluwatomiwa A.; Yu, Tianyu; Cai, Xiaoming; Jiang, Yue; Peng, Guotao; Cheng, Xiaomei; Li, Ruibin; Qin, Yao; Lin, Sijie

2018-06-01

The photocatalytic activity of TiO2 based photocatalysts can be improved by structural modification and elemental doping. In this study, through rational design, one type of carbon and nitrogen co-doped TiO2 (C, N-TiO2) photocatalyst with mesoporous structure was synthesized with improved photocatalytic activity in degrading 4-nitrophenol under simulated sunlight irradiation. The photocatalytic degradation efficiency of the C, N-TiO2 was much higher than the anatase TiO2 (A-TiO2) based on absorbance and HPLC analyses. Moreover, using zebrafish embryos, we showed that the intermediate degradation compounds generated by photocatalytic degradation of 4-nitrophenol had higher toxicity than the parent compound. A repeated degradation process was necessary to render complete degradation and non-toxicity to the zebrafish embryos. Our results demonstrated the importance of evaluating the photocatalytic degradation efficiency in conjunction with the toxicity assessment of the degradation compounds.

Toxicity of compounds with endocrine activity in the OECD 421 reproductive toxicity screening test

NARCIS (Netherlands)

Piersma AH; Verhoef A; Elvers LH; Wester PW; LEO; LPI

1998-01-01

The issue of endocrine disruption has, in view of human risk assessment, raised the question on whether more sensitive test methods are needed to detect the reproductive toxic properties of xenobiotic compounds with endocrine properties. We studied six known and alleged endocrine disruptors in an

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

International Nuclear Information System (INIS)

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

2012-01-01

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.

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: Peter.Theunissen@rivm.nl [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)

2012-08-01

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.

Can Dietary Polyphenols Prevent the Formation of Toxic Compounds from Maillard Reaction?

Science.gov (United States)

Del Turco, Serena; Basta, Giuseppina

2016-01-01

Polyphenols are functional compounds in edible vegetable and food such as tea, coffee and red wine and increasing evidence demonstrates a positive link between consumption of polyphenol-rich foods and disease prevention. In this review we have focused on the current knowledge of the potential anti-glycation effects of polyphenols, particularly in regard to their influence on Maillard reaction, a non-enzymatic reaction between amino acids and reducing sugars that contributes to the production of toxic compounds, mainly reactive carbonyl species, advanced glycation end-products (AGEs) and other toxicants. The Maillard reaction occurs in the human body during hyperglycemic condition, but it is well known as browning reaction in thermally processed foods and it is responsible for flavor and toxicant formation. Dietary polyphenols can have anti-glycation effects and actively participate in Maillard reaction, mitigating the AGE formation and the heat-induced production of toxic compounds. In a time in which the role of a healthy diet in the prevention of chronic diseases is welcome and the borderline between food and medicine is becoming very thin, an improved mechanistic knowledge of how polyphenols can function to reduce harmful and unhealthy substances is mandatory.

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

International Nuclear Information System (INIS)

Anh, Tuan Mai; Dzyadevych, Sergei V.; Prieur, Nicolas; Duc, Chien Nguyen; Pham, T.D.; Renault, Nicole Jaffrezic; Chovelon, Jean-Marc

2006-01-01

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

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: chovelon@univ-lyon1.fr

2006-03-15

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.

Identifying developmental vascular disruptor compounds using a predictive signature and alternative toxicity models

Science.gov (United States)

Identifying Developmental Vascular Disruptor Compounds Using a Predictive Signature and Alternative Toxicity Models Presenting Author: Tamara Tal Affiliation: U.S. EPA/ORD/ISTD, RTP, NC, USA Chemically induced vascular toxicity during embryonic development can result in a wide...

Identification of water soluble and particle bound compounds causing sublethal toxic effects. A field study on sediments affected by a chlor-alkali industry

International Nuclear Information System (INIS)

Bosch, Carme; Olivares, Alba; Faria, Melissa; Navas, Jose M.; Olmo, Ivan del; Grimalt, Joan O.; Pina, Benjamin; Barata, Carlos

2009-01-01

A combination of cost effective sublethal Daphnia magna feeding tests, yeast- and cell culture-based bioassays and Toxicity Identification Evaluation (TIE) procedures was used to characterize toxic compounds within sediments collected in a river area under the influence of the effluents from a chlor-alkali industry (Ebro River, NE Spain). Tests were designed to measure and identify toxic compounds in the particulate and filtered water fractions of sediment elutriates. The combined use of bioassays responding to elutriates and dioxin-like compounds evidenced the existence of three major groups of hazardous contaminants in the most contaminated site: (A) metals such as cadmium and mercury bound to sediment fine particles that could be easily resuspended and moved downstream, (B) soluble compounds (presumably, lye) able to alkalinize water to toxic levels, and (C) organochlorine compounds with high dioxin-like activity. These results provided evidence that elutriate D. magna feeding responses can be used as surrogate assays for more tedious chronic whole sediment tests, and that the incorporation of such tests in sediment TIE procedures may improve the ability to identify the toxicity of particle-bound and water-soluble contaminants in sediments.

Development of a toxicity-based fractionation approach for the identification of phototoxic PAHs in pore water

International Nuclear Information System (INIS)

Kosian, P.A.; Makynen, E.A.; Ankley, G.T.; Monson, P.D.

1995-01-01

Environmental matrices often contain complex mixtures of chemical compounds, however, typically only a few chemicals are responsible for observed toxicity. To determine those chemicals responsible for toxicity, a toxicity-based fractionation technique coupled with gas chromatography/mass spectrometry (GC/MS) has been used for the isolation and identification of nonpolar toxicants in aqueous samples. In this study, this technique was modified to separate and identify polycyclic aromatic hydrocarbons (PAHs) responsible for phototoxicity in pore water. Whole pore water, obtained from sediments collected near an oil refinery discharge site, was found to be toxic to Lumbriculus variegatus in the presence of ultraviolet (UV) light. Solid phase extraction disks and high pressure liquid chromatography were used, in conjunction with toxicity tests with L. variegatus, to extract and fractionate phototoxic chemicals from the pore water. GC/MS analysis was performed on the toxic fractions and a tentative list of compound identifications were made based on interpretation of mass spectra and elution information from the chromatographic separation. The compounds identified include PAHs and substituted PAHs that are known or predicted to be phototoxic in the presence of UV light. The results show that a modified toxicity-based fractionation approach can be successfully applied to identify phototoxic PAHs in sediment pore water and therefore used in the assessment of contaminated sediments

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))

2010-07-01

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

The application of FEL-EXPERT system in the interpretation of boron compounds toxicity

International Nuclear Information System (INIS)

Strouf, O.; Marik, V.

1990-01-01

The effect of substructural features of boron compounds on their toxicity (LD 50 , mice, i.p.) was studied using the FEL-EXPERT system developed by the Czech Technical University of Prague. A set of 108 compounds containing one or two boron atoms in their molecule was arbitrarily divided into three classes: compounds with high toxicity (LD 50 50 50 ≥1000 mg/kg). The compounds were represented by 70 substructural fragments, 27 of them being ''central substructures'' containing boron atom(s). The inference net consisted of 118 nodes (74 of the Bayesian type), 362 production rules and 74 context links. The total classification correctness was 98%. As a case-study, the classification of p-tolylboronic acid (LD 50 =520 mg/kg) and 4-carboxyphenylboronic acid (LD 50 =3838 mg/kg) was discussed. 4 figs., 2 tabs., 11 refs

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)

1997-11-10

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.

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

Science.gov (United States)

Alves, L; Paixão, S M

2011-10-01

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

Toxicity of six heterocyclic nitrogen compounds to Daphnia pulex

Science.gov (United States)

Perry, Cynthia M.; Smith, Stephen B.

1988-01-01

We determined the relative toxicities to the aquatic crustacean Daphniz pulex of six heterocyclic nitrogen compunds. These compounds were selected because they were detected in lake trout or walleyes and were commercially available. Stress to the daphnid populations may affect forage fish populations that depend either directly or indirectly on zooplankton as a food source in the Great Lakes.

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

Directory of Open Access Journals (Sweden)

Pick Neora

2004-01-01

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.

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

Science.gov (United States)

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

2013-05-01

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.

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

KAUST Repository

Essack, Magbubah

2014-10-29

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

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

KAUST Repository

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

2014-01-01

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

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

Science.gov (United States)

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

2014-01-01

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review. PMID:25356733

Microbial Fuels Cell-Based Biosensor for Toxicity Detection: A Review

Directory of Open Access Journals (Sweden)

Tuoyu Zhou

2017-09-01

Full Text Available With the unprecedented deterioration of environmental quality, rapid recognition of toxic compounds is paramount for performing in situ real-time monitoring. Although several analytical techniques based on electrochemistry or biosensors have been developed for the detection of toxic compounds, most of them are time-consuming, inaccurate, or cumbersome for practical applications. More recently, microbial fuel cell (MFC-based biosensors have drawn increasing interest due to their sustainability and cost-effectiveness, with applications ranging from the monitoring of anaerobic digestion process parameters (VFA to water quality detection (e.g., COD, BOD. When a MFC runs under correct conditions, the voltage generated is correlated with the amount of a given substrate. Based on this linear relationship, several studies have demonstrated that MFC-based biosensors could detect heavy metals such as copper, chromium, or zinc, as well as organic compounds, including p-nitrophenol (PNP, formaldehyde and levofloxacin. Both bacterial consortia and single strains can be used to develop MFC-based biosensors. Biosensors with single strains show several advantages over systems integrating bacterial consortia, such as selectivity and stability. One of the limitations of such sensors is that the detection range usually exceeds the actual pollution level. Therefore, improving their sensitivity is the most important for widespread application. Nonetheless, MFC-based biosensors represent a promising approach towards single pollutant detection.

Understanding the tolerance of the industrial yeast Saccharomyces cerevisiae against a major class of toxic aldehyde compounds.

Science.gov (United States)

Liu, ZongLin Lewis

2018-07-01

Development of the next-generation biocatalyst is vital for fermentation-based industrial applications and a sustainable bio-based economy. Overcoming the major class of toxic compounds associated with lignocellulose-to-biofuels conversion is one of the significant challenges for new strain development. A significant number of investigations have been made to understand mechanisms of the tolerance for industrial yeast. It is humbling to learn how complicated the cell's response to the toxic chemicals is and how little we have known about yeast tolerance in the universe of the living cell. This study updates our current knowledge on the tolerance of industrial yeast against aldehyde inhibitory compounds at cellular, molecular and the genomic levels. It is comprehensive yet specific based on reproducible evidence and cross confirmed findings from different investigations using varied experimental approaches. This research approaches a rational foundation toward a more comprehensive understanding on the yeast tolerance. Discussions and perspectives are also proposed for continued exploring the puzzle of the yeast tolerance to aid the next-generation biocatalyst development.

Does lipophilicity of toxic compounds determine effects on drought tolerance of the soil collembolan Folsomia candida?

International Nuclear Information System (INIS)

Skovlund, Gitte; Damgaard, Christian; Bayley, Mark; Holmstrup, Martin

2006-01-01

The ability of Collembola to survive drought stress is crucial for their distribution in the terrestrial environment. Previous studies have suggested that several toxic compounds affect the drought tolerance of Folsomia candida in a synergistic manner and that these compounds have the feature in common that they elicit their toxicity by causing membrane damage. We hypothesised that the detrimental effect of toxic chemicals on drought tolerance in F. candida depends on the lipophilicity (log K ow ) of the compound because a higher log K ow would mean a closer interaction with membranes. In this study the three chemicals 4-nonylphenol, pyrene and p,p'-DDE were tested. Surprisingly, 4-nonylphenol, with the lowest log K ow , was the most potent with respect to reducing drought tolerance followed by pyrene, suggesting that interactions between drought tolerance and chemical stress do not depend on lipophilicity alone. - Toxic stress may reduce drought tolerance of Collembola

Ionisation detectors as monitors of toxic compounds in air

International Nuclear Information System (INIS)

Leonhardt, J.W.

1994-01-01

Beta particles cause ionisation in gas mixtures. The ions produced provide information on the concentration and identity of trace compounds in ambient air. Modern ionisation detectors use ion mobilities to monitor toxic compounds. Chemical solvent, phosphororganic compounds, PCB and many other toxins can be detected using ion mobility detectors (IMD) in the ppb range or lower. Ion mobility detectors have large potential in industry and research because of their sensitivity, specificity, fast response and relatively low cost. Portable devices and fixed installations are possible. The paper discusses the following topics: (1) ionisation sources in IMD: 63 Ni, 3 H, photoionization and corona discharge, (2) basic principles of ion production, (3) ion collection in IMD, (4) design, gas supply, automatic identification and quantification of IMD data, and (5) selected applications. Advantages and problems with this new type of nuclear analytical instrument are also discussed. (author). 2 refs., 9 figs., 3 tabs

Solar driven production of toxic halogenated and nitroaromatic compounds in natural seawater

Energy Technology Data Exchange (ETDEWEB)

Calza, Paola [Dipartimento di Chimica Analitica, Universita di Torino, via P. Giuria 5, 10125 Torino (Italy)], E-mail: paola.calza@unito.it; Massolino, Cristina; Pelizzetti, Ezio; Minero, Claudio [Dipartimento di Chimica Analitica, Universita di Torino, via P. Giuria 5, 10125 Torino (Italy)

2008-07-15

Natural seawater (NSW) sampled in March and June 2007 in the Gulf of Trieste, Italy, has been spiked with phenol and irradiated in a device simulating solar light spectrum and intensity. Opposite to the case of artificial seawater, for which phenol is slightly degraded by direct photolysis, in NSW the phenol degradation mediated by natural photosensitizers occurs, forming several secondary pollutants, including hydroxyderivatives (1,4-benzoquinone, resorcinol), three chlorophenol isomers, 2,3-dichlorophenol, 2- and 4-bromophenol, 2- and 4-nitrophenol, and several condensed products (2 and 4-phenoxyphenol, 2,2'-, 4,4'- and 2,4-bisphenol). These compounds are toxic to bacteria and other living organisms. Ecotoxicologic effect has been evaluated by using the Vibrio Fischeri luminescent bacteria assay. This technique uses marine organisms, and it is therefore well suited for the study on marine samples. A correlation exists between the intermediates evolution and the toxicity profile, as the largest toxicity is observed when compounds with the lower EC50 (halophenols, phenoxyphenols) are formed at higher concentration.

Solar driven production of toxic halogenated and nitroaromatic compounds in natural seawater

International Nuclear Information System (INIS)

Calza, Paola; Massolino, Cristina; Pelizzetti, Ezio; Minero, Claudio

2008-01-01

Natural seawater (NSW) sampled in March and June 2007 in the Gulf of Trieste, Italy, has been spiked with phenol and irradiated in a device simulating solar light spectrum and intensity. Opposite to the case of artificial seawater, for which phenol is slightly degraded by direct photolysis, in NSW the phenol degradation mediated by natural photosensitizers occurs, forming several secondary pollutants, including hydroxyderivatives (1,4-benzoquinone, resorcinol), three chlorophenol isomers, 2,3-dichlorophenol, 2- and 4-bromophenol, 2- and 4-nitrophenol, and several condensed products (2 and 4-phenoxyphenol, 2,2'-, 4,4'- and 2,4-bisphenol). These compounds are toxic to bacteria and other living organisms. Ecotoxicologic effect has been evaluated by using the Vibrio Fischeri luminescent bacteria assay. This technique uses marine organisms, and it is therefore well suited for the study on marine samples. A correlation exists between the intermediates evolution and the toxicity profile, as the largest toxicity is observed when compounds with the lower EC50 (halophenols, phenoxyphenols) are formed at higher concentration

Sanitary Assessment of Hazardous Materials Exposed To Highly Toxic Chemical Compounds

International Nuclear Information System (INIS)

Rembovskiy, V.; Ermolaeva, E.

2007-01-01

-and-plant microflora and hydrocoles. 4. Development of non-standard methodical approaches when determining and interpreting the hazard classes of the wastes, containing high toxic compounds such as nerve gases. In particular, disembodied methods applied for solving the tasks of assessment of chemical compounds toxicity were summarized, as well as a uniform scheme of experimental toxicological assessment of TC of a high risk is presented. A system of quantitative assessment of the TC risk is developed on the basis of integral coefficient of risk (KTC), thus simplifying decision making after toxicological testing. Calculation of the coefficient of the TC risk is based on logarithm of ratio of toxicometry parameters to the value of identical parameters determining affiliation of the TC to the 1st class of risk (extreme risk). Due to the methodology developed in our Institute, we have for the first time estimated the class of toxicity of a highly complicated industrial system. (author)

Toxicity assessment of volatile organic compounds and polycyclic aromatic hydrocarbons in motorcycle exhaust.

Science.gov (United States)

Chang, Chang-Tang; Chen, Bor-Yann

2008-05-30

This study investigates the toxicity of various pollutant species from motorcycle exhaust via dose-response analysis and margin of safety using Escherichia coli DH5 alpha. The toxicity evaluation of the major components of motorcycle exhaust volatile organic compounds (VOCs), collected with impinger, and polycyclic aromatic hydrocarbons (PAHs), collected with filter and XAD-2, is essential to determine emission standards for motorcycles. The toxicity of benzene (B), toluene (T), ethyl benzene (E) and xylene (X) was selected for comparison as standard VOCs emitted from motorcycles. In addition, three types of reformulated gasoline (high oxygenate and high benzene content (No. 1), low oxygen and high benzene (No. 2), and low oxygen and low benzene (No. 3) were prepared to reveal combined toxicity of individual compositions. Motorcycle exhaust is significantly more toxic than BTEX due to the highly toxic VOCs generated from incomplete combustion. Overall toxicity evaluation showed that the toxicity, indicated as EC50, was approximately as follows: PAHs>two-stroke engines>four-stroke engines>BTEX.

Toxicity assessment of volatile organic compounds and polycyclic aromatic hydrocarbons in motorcycle exhaust

International Nuclear Information System (INIS)

Chang, C.-T.; Chen, B.-Y.

2008-01-01

This study investigates the toxicity of various pollutant species from motorcycle exhaust via dose-response analysis and margin of safety using Escherichia coli DH5α. The toxicity evaluation of the major components of motorcycle exhaust volatile organic compounds (VOCs), collected with impinger, and polycyclic aromatic hydrocarbons (PAHs), collected with filter and XAD-2, is essential to determine emission standards for motorcycles. The toxicity of benzene (B), toluene (T), ethyl benzene (E) and xylene (X) was selected for comparison as standard VOCs emitted from motorcycles. In addition, three types of reformulated gasoline (high oxygenate and high benzene content (No. 1), low oxygen and high benzene (No. 2), and low oxygen and low benzene (No. 3) were prepared to reveal combined toxicity of individual compositions. Motorcycle exhaust is significantly more toxic than BTEX due to the highly toxic VOCs generated from incomplete combustion. Overall toxicity evaluation showed that the toxicity, indicated as EC 50 , was approximately as follows: PAHs > two-stroke engines > four-stroke engines > BTEX

Discriminating modes of toxic action in mice using toxicity in BALB/c mouse fibroblast (3T3) cells.

Science.gov (United States)

Huang, Tao; Yan, Lichen; Zheng, Shanshan; Wang, Yue; Wang, Xiaohong; Fan, Lingyun; Li, Chao; Zhao, Yuanhui; Martyniuk, Christopher J

2017-12-01

The objective of this study was to determine whether toxicity in mouse fibroblast cells (3T3 cells) could predict toxicity in mice. Synthesized data on toxicity was subjected to regression analysis and it was observed that relationship of toxicities between mice and 3T3 cells was not strong (R 2  = 0.41). Inclusion of molecular descriptors (e.g. ionization, pKa) improved the regression to R 2  = 0.56, indicating that this relationship is influenced by kinetic processes of chemicals or specific toxic mechanisms associated to the compounds. However, to determine if we were able to discriminate modes of action (MOAs) in mice using the toxicities generated from 3T3 cells, compounds were first classified into "baseline" and "reactive" guided by the toxic ratio (TR) for each compound in mice. Sequence, binomial and recursive partitioning analyses provided strong predictions of MOAs in mice based upon toxicities in 3T3 cells. The correct classification of MOAs based on these methods was 86%. Nearly all the baseline compounds predicted from toxicities in 3T3 cells were identified as baseline compounds from the TR in mice. The incorrect assignment of MOAs for some compounds is hypothesized to be due to experimental uncertainty that exists in toxicity assays for both mice and 3T3 cells. Conversely, lack of assignment can also arise because some reactive compounds have MOAs that are different in mice compared to 3T3 cells. The methods developed here are novel and contribute to efforts to reduce animal numbers in toxicity tests that are used to evaluate risks associated with organic pollutants in the environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Julio Alonso-Padilla

2015-01-01

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.

Rubber (Hevea brasiliensis) seed oil toxicity effect and Linamarin compound analysis.

Science.gov (United States)

Salimon, Jumat; Abdullah, Bashar Mudhaffar; Salih, Nadia

2012-06-13

The lipid fraction of rubber (Hevea brasiliensis (kunth. Muell)) seed was extracted and analyzed for toxicological effect. The toxicological compound such as linamarin in rubber seed oil (RSO) extracted using different solvents, such as hexane (RSOh), mixture of chloroform + methanol (RSOchl+mth) and ethanol (RSOeth) were also studied. Various methods analysis such as Fourier transforms infrared spectroscopy (FTIR) and colorimetric methods were carried out to determine the present of such compounds. FTIR spectrum of RSO did not show any presence of cyanide peak. The determination of cyanide by using colorimetric method was demonstrated no response of the cyanide in RSO and didn't show any colored comparing with commercial cyanide which observed blue color. The results showed that no functional groups such as cyanide (C ≡ N) associated with linamarin were observed. Toxicological test using rats was also conducted to further confirm the absence of such compounds. RSO did not show any toxic potential to the rats. Bioassay experiments using shrimps had been used as test organisms to evaluate the toxicity of linamarin extract from RSO(h,) RSO(chl+mth) and RSO(eth) and LC50 were found to be (211.70 %, 139.40 %, and 117.41 %, respectively). This can be attributed no hazardous linamarin were found in RSO.

MONITORING THE AIR FOR TOXIC AND GENOTOXIC COMPOUNDS

Science.gov (United States)

A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor p...

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

Science.gov (United States)

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

2013-01-01

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

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

Science.gov (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

2013-06-01

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.

Low-Toxicity Diindol-3-ylmethanes as Potent Antifouling Compounds.

Science.gov (United States)

Wang, Kai-Ling; Xu, Ying; Lu, Liang; Li, Yongxin; Han, Zhuang; Zhang, Jun; Shao, Chang-Lun; Wang, Chang-Yun; Qian, Pei-Yuan

2015-10-01

In the present study, eight natural products that belonged to di(1H-indol-3-yl)methane (DIM) family were isolated from Pseudovibrio denitrificans UST4-50 and tested for their antifouling activity against larval settlement (including both attachment and metamorphosis) of the barnacle Balanus (=Amphibalanus) amphitrite and the bryozoan Bugula neritina. All diindol-3-ylmethanes (DIMs) showed moderate to strong inhibitory effects against larval settlement of B. amphitrite with EC50 values ranging from 18.57 to 1.86 μM and could be considered as low-toxicity antifouling compounds since their LC50/EC50 ratios were larger than 15. Furthermore, the DIM- and 4-(di(1H-indol-3-yl)methyl)phenol (DIM-Ph-4-OH)-treated larvae completed normal settlement when they were transferred to clean seawater after being exposed to those compounds for 24 h. DIM also showed comparable antifouling performance to the commercial antifouling biocide Sea-Nine 211(™) in the field test over a period of 5 months, which further confirmed that DIMs can be considered as promising candidates of environmentally friendly antifouling compounds.

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

KAUST Repository

Zhang, Yi-Fan

2011-08-29

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.

Rubber (Hevea brasiliensis seed oil toxicity effect and Linamarin compound analysis

Directory of Open Access Journals (Sweden)

Salimon Jumat

2012-06-01

Full Text Available Abstract Background The lipid fraction of rubber (Hevea brasiliensis (kunth. Muell seed was extracted and analyzed for toxicological effect. The toxicological compound such as linamarin in rubber seed oil (RSO extracted using different solvents, such as hexane (RSOh, mixture of chloroform + methanol (RSOchl+mth and ethanol (RSOeth were also studied. Various methods analysis such as Fourier transforms infrared spectroscopy (FTIR and colorimetric methods were carried out to determine the present of such compounds. Results FTIR spectrum of RSO did not show any presence of cyanide peak. The determination of cyanide by using colorimetric method was demonstrated no response of the cyanide in RSO and didn’t show any colored comparing with commercial cyanide which observed blue color. The results showed that no functional groups such as cyanide (C ≡ N associated with linamarin were observed. Toxicological test using rats was also conducted to further confirm the absence of such compounds. RSO did not show any toxic potential to the rats. Bioassay experiments using shrimps had been used as test organisms to evaluate the toxicity of linamarin extract from RSOh, RSOchl+mth and RSOeth and LC50 were found to be (211.70 %, 139.40 %, and 117.41 %, respectively. Conclusions This can be attributed no hazardous linamarin were found in RSO.

Biological Mimics: A New Paradigm in the Detection of Toxic Compounds

Science.gov (United States)

Monty, Chelsea Nicole

2009-01-01

The purpose of this thesis is to introduce a new idea: using biological mimics in the detection of toxic compounds. Biological mimics imitate the active site of a given enzyme or have catalytic chemistry similar to enzymes and can be used in place of biological molecules to provide longer stability and simpler operation. In the following text the…

Effect of perfluorooctane sulfonate on toxicity and cell uptake of other compounds with different hydrophobicity in green alga.

Science.gov (United States)

Liu, Wei; Zhang, Yao-Bin; Quan, Xie; Jin, Yi-He; Chen, Shuo

2009-04-01

Perfluorooctane sulfonate (PFOS) was evaluated alone and in binary mixtures with pentachlorophenol, atrazine and diuron, respectively to investigate the effects of interactions between PFOS and other compounds on the growth rate in Scenedesmus obliquus. Single application of PFOS showed no inhibition on the growth of S. obliquus below 40 mg L(-1), whereas PFOS acting with pentachlorophenol resulted in higher algal growth inhibition in comparison with pentachlorophenol alone. A maximum increase of 45% in the growth inhibition was observed at a pentachlorophenol concentration of 2.56 mg L(-1) together with a PFOS concentration of 40 mg L(-1). On the contrary, the algal growth inhibition of atrazine and diuron was depressed by PFOS. Furthermore, cell uptake was examined to gain some insights into the mechanisms of the effects of PFOS on the toxicity of the other compounds. Cell uptake of pentachlorophenol increased while that of atrazine and diuron was reduced in cells that have been exposed to PFOS. The effects of PFOS on the toxicity of pentachlorophenol, atrazine and diuron were possibly related to the influence of PFOS on the cell uptake of these hydrophobic compounds. Results suggested that PFOS influenced the cell uptake and toxicity of structurally different compounds in dissimilar manners and potentially increased the accessibility and toxicity of more hydrophobic compounds to algal cells.

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

International Nuclear Information System (INIS)

Rodriguez Castillo, Alfredo Santiago; Guihéneuf, Solène; Le Guével, Rémy; Biard, Pierre-François

2016-01-01

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_6"−, NTf_2"− 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 BOD_2_8 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.

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

Science.gov (United States)

Banerjee, Priyanka; Preissner, Robert

2018-04-01

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

Repeated-dose toxicological studies of Tithonia diversifolia (Hemsl.) A. gray and identification of the toxic compounds.

Science.gov (United States)

Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista

2013-05-20

Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Wu Dong

2016-08-01

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.

[Optimization of solid-phase extraction for enrichment of toxic organic compounds in water samples].

Science.gov (United States)

Zhang, Ming-quan; Li, Feng-min; Wu, Qian-yuan; Hu, Hong-ying

2013-05-01

A concentration method for enrichment of toxic organic compounds in water samples has been developed based on combined solid-phase extraction (SPE) to reduce impurities and improve recoveries of target compounds. This SPE method was evaluated in every stage to identify the source of impurities. Based on the analysis of Waters Oasis HLB without water samples, the eluent of SPE sorbent after dichloromethane and acetone contributed 85% of impurities during SPE process. In order to reduce the impurities from SPE sorbent, soxhlet extraction of dichloromethane followed by acetone and lastly methanol was applied to the sorbents for 24 hours and the results had proven that impurities were reduced significantly. In addition to soxhlet extraction, six types of prevalent SPE sorbents were used to absorb 40 target compounds, the lgK(ow) values of which were within the range of 1.46 and 8.1, and recovery rates were compared. It was noticed and confirmed that Waters Oasis HLB had shown the best recovery results for most of the common testing samples among all three styrenedivinylbenzene (SDB) polymer sorbents, which were 77% on average. Furthermore, Waters SepPak AC-2 provided good recovery results for pesticides among three types of activated carbon sorbents and the average recovery rates reached 74%. Therefore, Waters Oasis HLB and Waters SepPak AC-2 were combined to obtain a better recovery and the average recovery rate for the tested 40 compounds of this new SPE method was 87%.

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: solene.guiheneuf@wanadoo.fr [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

2016-04-15

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.

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

Science.gov (United States)

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

2016-01-01

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.

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

International Nuclear Information System (INIS)

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

2000-01-01

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

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

Science.gov (United States)

Umysová, Dáša; Vítová, Milada; Doušková, Irena; Bišová, Kateřina; Hlavová, Monika; Čížková, Mária; Machát, Jiří; Doucha, Jiří; Zachleder, Vilém

2009-01-01

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. Our study provides a new

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

Directory of Open Access Journals (Sweden)

Doucha Jiří

2009-05-01

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

Current data regarding the structure-toxicity relationship of boron-containing compounds.

Science.gov (United States)

Farfán-García, E D; Castillo-Mendieta, N T; Ciprés-Flores, F J; Padilla-Martínez, I I; Trujillo-Ferrara, J G; Soriano-Ursúa, M A

2016-09-06

Boron is ubiquitous in nature, being an essential element of diverse cells. As a result, humans have had contact with boron containing compounds (BCCs) for a long time. During the 20th century, BCCs were developed as antiseptics, antibiotics, cosmetics and insecticides. Boric acid was freely used in the nosocomial environment as an antiseptic and sedative salt, leading to the death of patients and an important discovery about its critical toxicology for humans. Since then the many toxicological studies done in relation to BCCs have helped to establish the proper limits of their use. During the last 15 years, there has been a boom of research on the design and use of new, potent and efficient boron containing drugs, finding that the addition of boron to some known drugs increases their affinity and selectivity. This mini-review summarizes two aspects of BCCs: toxicological data found with experimental models, and the scarce but increasing data about the structure-activity relationship for toxicity and therapeutic use. As is the case with boron-free compounds, the biological activity of BCCs is related to their chemical structure. We discuss the use of new technology to discover potent and efficient BCCs for medicinal therapy by avoiding toxic effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

New Approaches for the Synthesis, Cytotoxicity and Toxicity of Heterocyclic Compounds Derived from 2-Cyanomethylbenzo[c]imidazole.

Science.gov (United States)

Mohareb, Rafat M; Mohamed, Abeer A; Abdallah, Amira E M

2016-01-01

The reaction of ethyl cyanoacetate with o-phenylenediamine gave the 2-cyanomethylbenzo[c]imidazole (1). The latter compound was used as the key starting material to synthesise biologically active heterocyclic derivatives. Thus, the reaction of 1 with cyclohexanone and either of benzaldehyde, 4-methoxybenzaldehyde or 4-chlorobenzaldehyde gave the annulated derivatives 2a-c, respectively. The antitumor evaluations of the newly synthesized products against the three cancer cell lines MCF-7 (breast adeno-carcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer) showed that compounds 2b, 6, 11b, 11c, 12b, 16a, 16b and 18a exhibited optimal cytotoxic effect against cancer cell lines, with IC50 values in the nM range. Bioactive compounds are often toxic to shrimp larvae. Thus, in order to monitor these chemicals in vivo lethality to shrimp larvae (Artemia salina), Brine-Shrimp Lethality Assay was used. Compounds 11b, 12b and 16b showed no toxicity against the tested organisms.

Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

Science.gov (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

2016-08-01

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>LD50compound 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. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigations of chemical warfare agents and toxic industrial compounds with proton-transfer-reaction mass spectrometry for a real-time threat monitoring scenario.

Science.gov (United States)

Kassebacher, Thomas; Sulzer, Philipp; Jürschik, Simone; Hartungen, Eugen; Jordan, Alfons; Edtbauer, Achim; Feil, Stefan; Hanel, Gernot; Jaksch, Stefan; Märk, Lukas; Mayhew, Chris A; Märk, Tilmann D

2013-01-30

Security and protection against terrorist attacks are major issues in modern society. One especially challenging task is the monitoring and protection of air conditioning and heating systems of buildings against terrorist attacks with toxic chemicals. As existing technologies have low selectivity, long response times or insufficient sensitivity, there is a need for a novel approach such as we present here. We have analyzed various chemical warfare agents (CWAs) and/or toxic industrial compounds (TICs) and related compounds, namely phosgene, diphosgene, chloroacetone, chloroacetophenone, diisopropylaminoethanol, and triethyl phosphate, utilizing a high-resolution proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) instrument with the objective of finding key product ions and their intensities, which will allow a low-resolution quadrupole mass spectrometry based PTR-MS system to be used with high confidence in the assignment of threat agents in the atmosphere. We obtained high accuracy PTR-TOFMS mass spectra of the six compounds under study at two different values for the reduced electric field in the drift tube (E/N). From these data we have compiled a table containing product ions, and isotopic and E/N ratios for highly selective threat compound detection with a compact and cost-effective quadrupole-based PTR-MS instrument. Furthermore, using chloroacetophenone (tear gas), we demonstrated that this instrument's response is highly linear in the concentration range of typical Acute Exposure Guideline Levels (AEGLs). On the basis of the presented results it is possible to develop a compact and cost-effective PTR-QMS instrument that monitors air supply systems and triggers an alarm as soon as the presence of a threat agent is detected. We hope that this real-time surveillance device will help to seriously improve safety and security in environments vulnerable to terrorist attacks with toxic chemicals. Copyright © 2012 John Wiley & Sons, Ltd.

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

KAUST Repository

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

2015-01-01

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.

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

KAUST Repository

Jin, Peng

2015-10-27

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.

The Study and Development of Metal Oxide Reactive Adsorbents for the Destruction of Toxic Organic Compounds

National Research Council Canada - National Science Library

Mitchell, Mark B

2008-01-01

... and other toxic organic compounds. The research program that was developed built upon earlier results achieved in the room temperature oxidative decomposition of a chemical warfare agent simulant, dimethyl methylphosphonate (DMMP...

Development of thresholds of excess toxicity for environmental species and their application to identification of modes of acute toxic action.

Science.gov (United States)

Li, Jin J; Zhang, Xu J; Yang, Yi; Huang, Tao; Li, Chao; Su, Limin; Zhao, Yuan H; Cronin, Mark T D

2018-03-01

The acute toxicity of organic pollutants to fish, Daphnia magna, Tetrahymena pyriformis, and Vibrio fischeri was investigated. The results indicated that the Toxicity Ratio (TR) threshold of log TR =1, which has been based on the distribution of toxicity data to fish, can also be used to discriminate reactive or specifically acting compounds from baseline narcotics for Daphnia magna and Vibrio fischeri. A log TR=0.84 is proposed for Tetrahymena pyriformis following investigation of the relationships between the species sensitivity and the absolute averaged residuals (AAR) between the predicted baseline toxicity and the experimental toxicity. Less inert compounds exhibit relatively higher toxicity to the lower species (Tetrahymena pyriformis and Vibrio fischeri) than the higher species (fish and Daphnia magna). A greater number of less inert compounds with log TR greater than the thresholds was observed for Tetrahymena pyriformis and Vibrio fischeri. This may be attributed to the hydrophilic compounds which may pass more easily through cell membranes than the skin or exoskeleton of organisms and have higher bioconcentration factors in the lower species, leading to higher toxicity. Most of classes of chemical associated with excess toxicity to one species also exhibited excess toxicity to other species, however, a few classes with excess toxicity to one species exhibiting narcotic toxicity to other species and thus may have different MOAs between species. Some ionizable compounds have log TR much lower than one because of the over-estimated log K OW . The factors that influence the toxicity ratio calculated from baseline level are discussed in this paper. Copyright © 2017 Elsevier B.V. All rights reserved.

Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

Science.gov (United States)

Wang, Xu; Wu, Qinghua; Liu, Aimei; Anadón, Arturo; Rodríguez, José-Luis; Martínez-Larrañaga, María-Rosa; Yuan, Zonghui; Martínez, María-Aránzazu

2017-11-01

Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

The discovery of bioisoster compound for plumbagin using the knowledge-based rational method

Science.gov (United States)

Jeong, Seo Hee; Choi, Jung Sup; Ko, Young Kwan; Kang, Nam Sook

2015-04-01

Arabidopsis thaliana 7-Keto-8-AminoPelargonic Acid Synthase (AtKAPAS) is a crucial herbicide target, and AtKAPAS inhibitors are widely available in the agrochemical market. The herbicide plumbagin is known as a potent inhibitor for AtKAPAS but it is extremely toxic. In this study, we identified the metabolic site of plumbagin and also performed a similarity-based library analysis using 2D fingerprints and a docking study. Four compounds as virtual hits were derived from plumbagin. Treatment of Digitaria ciliaris with compound 2, one of four hit compounds, stunted the growth of leaves and the leaf tissue was desiccated or burned within three days. Thus, we expect that compound 2 will be developed as a new herbicide and additionally our strategy will provide helpful information for optimizing lead compounds.

Contact and fumigant toxicity of Armoracia rusticana essential oil, allyl isothiocyanate and related compounds to Dermatophagoides farinae.

Science.gov (United States)

Yun, Yeon-Kyeong; Kim, Hyun-Kyung; Kim, Jun-Ran; Hwang, Kumnara; Ahn, Young-Joon

2012-05-01

The toxicity to adult Dermatophagoides farinae of allyl isothiocyanate identified in horseradish, Armoracia rusticana, oil and another 27 organic isothiocyanates was evaluated using contact + fumigant and vapour-phase mortality bioassays. Results were compared with those of two conventional acaricides, benzyl benzoate and dibutyl phthalate. Horseradish oil (24 h LC(50), 1.54 µg cm(-2)) and allyl isothiocyanate (2.52 µg cm(-2)) were highly toxic. Benzyl isothiocyanate (LC(50) , 0.62 µg cm(-2)) was the most toxic compound, followed by 4-chlorophenyl, 3-bromophenyl, 3,5-bis(trifluoromethyl)phenyl, cyclohexyl, 2-chlorophenyl, 4-bromophenyl and 2-bromophenyl isothiocyanates (0.93-1.41 µg cm(-2)). All were more effective than either benzyl benzoate (LC(50) , 4.58 µg cm(-2)) or dibutyl phthalate (24.49 µg cm(-2)). The structure-activity relationship indicates that types of functional group and chemical structure appear to play a role in determining the isothiocyanate toxicities to adult D. farinae. In the vapour-phase mortality bioassay, these isothiocyanates were consistently more toxic in closed versus open containers, indicating that their mode of delivery was, in part, a result of vapour action. In the light of global efforts to reduce the level of highly toxic synthetic acaricides in indoor environments, the horseradish oil-derived compounds and the isothiocyanates described herein merit further study as potential acaricides for the control of house dust mite populations as fumigants with contact action. Copyright © 2011 Society of Chemical Industry.

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

International Nuclear Information System (INIS)

Sarró, Eduard; Jacobs-Cachá, Conxita; Itarte, Emilio; Meseguer, Anna

2012-01-01

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

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: eduard.sarro@vhir.org [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: conxita.jacobs@vhir.org [Renal Physiopathology, CIBBIM-Nanomedicine, Vall d' Hebron Research Institute (VHIR), 08035 Barcelona (Spain); Itarte, Emilio, E-mail: emili.itarte@uab.es [Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica de Biociències, Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Meseguer, Anna, E-mail: ana.meseguer@vhir.org [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)

2012-01-15

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

Speciation in Metal Toxicity and Metal-Based Therapeutics

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Douglas M. Templeton

2015-04-01

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.

Studies on the toxicity of RSU-1069

International Nuclear Information System (INIS)

Whitmore, G.F.; Gulyas, S.

1986-01-01

RSU-1069 combines an aziridine function with a 2-nitroimidazole and has been reported to exhibit extraordinary radiosensitization both in vitro and in vivo. Such sensitization appears to be at variance with the electron affinity of the compound. In addition, recent experiments suggest that the compound is highly toxic to hypoxic tumor cells in vivo. On the assumption that the observed radiosensitizing ability may be a manifestation of toxicity and because of the high in vivo toxicity, we have investigated aerobic and hypoxic toxicity, both in wild type CHO cells and in mutants sensitive to a variety of DNA damaging agents. With wild type cells under aerobic conditions, the compound is approximately 50 times as toxic as misonidazole and under hypoxic conditions, approximately 250 times as toxic. The ratio of hypoxic to aerobic toxicity is approximately 80 times. Under aerobic conditions, repair-deficient mutants are 10 times as sensitive to RSU-1069 as wild type cells and approximately 100 times as sensitive under hypoxic conditions. The ratio of hypoxic to aerobic toxicity for the mutant cells is approximately 900. Based on these observations, we suggest that under aerobic conditions the aziridine function is primarily responsible for toxicity, whereas, under hypoxic conditions, the aziridine moiety combined with a reduced 2-nitroimidazole moiety produces a bifunctional agent

Comparative investigation of toxicity and bioaccumulation of Cd-based quantum dots and Cd salt in freshwater plant Lemna minor L.

Science.gov (United States)

Modlitbová, Pavlína; Novotný, Karel; Pořízka, Pavel; Klus, Jakub; Lubal, Přemysl; Zlámalová-Gargošová, Helena; Kaiser, Jozef

2018-01-01

The purpose of this study was to determine the toxicity of two different sources of cadmium, i.e. CdCl 2 and Cd-based Quantum Dots (QDs), for freshwater model plant Lemna minor L. Cadmium telluride QDs were capped with two coating ligands: glutathione (GSH) or 3-mercaptopropionic acid (MPA). Growth rate inhibition and final biomass inhibition of L. minor after 168-h exposure were monitored as toxicity endpoints. Dose-response curves for Cd toxicity and EC50 168h values were statistically evaluated for all sources of Cd to uncover possible differences among the toxicities of tested compounds. Total Cd content and its bioaccumulation factors (BAFs) in L. minor after the exposure period were also determined to distinguish Cd bioaccumulation patterns with respect to different test compounds. Laser-Induced Breakdown Spectroscopy (LIBS) with lateral resolution of 200µm was employed in order to obtain two-dimensional maps of Cd spatial distribution in L. minor fronds. Our results show that GSH- and MPA-capped Cd-based QDs have similar toxicity for L. minor, but are significantly less toxic than CdCl 2 . However, both sources of Cd lead to similar patterns of Cd bioaccumulation and distribution in L. minor fronds. Our results are in line with previous reports that the main mediators of Cd toxicity and bioaccumulation in aquatic plants are Cd 2+ ions dissolved from Cd-based QDs. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparing rat and rabbit embryo-fetal developmental toxicity ...

Science.gov (United States)

A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n=283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and rabbit were equally sensitive. The relative extent of embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and rabbit studies. Individual rat and rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects betwe

Base catalyzed decomposition of toxic and hazardous chemicals

International Nuclear Information System (INIS)

Rogers, C.J.; Kornel, A.; Sparks, H.L.

1991-01-01

There are vast amounts of toxic and hazardous chemicals, which have pervaded our environment during the past fifty years, leaving us with serious, crucial problems of remediation and disposal. The accumulation of polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), ''dioxins'' and pesticides in soil sediments and living systems is a serious problem that is receiving considerable attention concerning the cancer-causing nature of these synthetic compounds.US EPA scientists developed in 1989 and 1990 two novel chemical Processes to effect the dehalogenation of chlorinated solvents, PCBs, PCDDs, PCDFs, PCP and other pollutants in soil, sludge, sediment and liquids. This improved technology employs hydrogen as a nucleophile to replace halogens on halogenated compounds. Hydrogen as nucleophile is not influenced by steric hinderance as with other nucleophile where complete dehalogenation of organohalogens can be achieved. This report discusses catalyzed decomposition of toxic and hazardous chemicals

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

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Jerzy Leszczynski

2000-10-01

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.

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

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Laszlo G. Puskas

2011-09-01

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

Potential carcinogenicity predicted by computational toxicity evaluation of thiophosphate pesticides using QSTR/QSCarciAR model.

Science.gov (United States)

Petrescu, Alina-Maria; Ilia, Gheorghe

2017-07-01

This study presents in silico prediction of toxic activities and carcinogenicity, represented by the potential carcinogenicity DSSTox/DBS, based on vector regression with a new Kernel activity, and correlating the predicted toxicity values through a QSAR model, namely: QSTR/QSCarciAR (quantitative structure toxicity relationship/quantitative structure carcinogenicity-activity relationship) described by 2D, 3D descriptors and biological descriptors. The results showed a connection between carcinogenicity (compared to the structure of a compound) and toxicity, as a basis for future studies on this subject, but each prediction is based on structurally similar compounds and the reactivation of the substructures of these compounds.

Quantitative structure-activity relationships for toxicity and genotoxicity of halogenated aliphatic compounds: wing spot test of Drosophila melanogaster.

Science.gov (United States)

Chroust, Karel; Pavlová, Martina; Prokop, Zbynek; Mendel, Jan; Bozková, Katerina; Kubát, Zdenek; Zajícková, Veronika; Damborský, Jiri

2007-02-01

Halogenated aliphatic compounds were evaluated for toxic and genotoxic effects in the somatic mutation and recombination test employing Drosophila melanogaster. The tested chemicals included chlorinated, brominated and iodinated; mono-, di- and tri-substituted; saturated and unsaturated alkanes: 1,2-dibromoethane, 1-bromo-2-chloroethane, 1-iodopropane, 2,3-dichloropropene, 3-bromo-1-propene, epibromohydrin, 2-iodobutane, 3-chloro-2-methylpropene, 1,2,3-trichloropropane, 1,2-dichloroethane, 1,2-dichlorobutane, 1-chloro-2-methylpropane, 1,3-dichloropropane, 1,2-dichloropropane, 2-chloroethymethylether, 1-bromo-2-methylpropane and 1-chloropentane. N-methyl-N-nitrosourea served as the positive and distilled water as the negative control. The set of chemicals for the toxicological testing was selected by the use of statistical experiment design. Group of unsaturated aliphatic hydrocarbons were generally more toxic than saturated analogues. The genotoxic effect was observed with 14 compounds in the wing spot test, while 3 substances did not show any genotoxicity by using the wing spot test at 50% lethal concentration. The highest number of wing spots was observed in genotoxicity assay with 1-bromo-2-chloroethane, 1,2-dichloroethane, 1,2-dibromoethane and 1-iodopropane. Nucleophilic superdelocalizability calculated by quantum mechanics appears to be a good parameter for prediction of both toxicity and genotoxicity effects of halogenated aliphatic compounds.

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

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Qi Zhi Liu

2011-08-01

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.

SEURAT-1 liver gold reference compounds: a mechanism-based review.

Science.gov (United States)

Jennings, Paul; Schwarz, Michael; Landesmann, Brigitte; Maggioni, Silvia; Goumenou, Marina; Bower, David; Leonard, Martin O; Wiseman, Jeffrey S

2014-12-01

There is an urgent need for the development of alternative methods to replace animal testing for the prediction of repeat dose chemical toxicity. To address this need, the European Commission and Cosmetics Europe have jointly funded a research program for 'Safety Evaluation Ultimately Replacing Animal Testing.' The goal of this program was the development of in vitro cellular systems and associated computational capabilities for the prediction of hepatic, cardiac, renal, neuronal, muscle, and skin toxicities. An essential component of this effort is the choice of appropriate reference compounds that can be used in the development and validation of assays. In this review, we focus on the selection of reference compounds for liver pathologies in the broad categories of cytotoxicity and lipid disorders. Mitochondrial impairment, oxidative stress, and apoptosis are considered under the category of cytotoxicity, while steatosis, cholestasis, and phospholipidosis are considered under the category of lipid dysregulation. We focused on four compound classes capable of initiating such events, i.e., chemically reactive compounds, compounds with specific cellular targets, compounds that modulate lipid regulatory networks, and compounds that disrupt the plasma membrane. We describe the molecular mechanisms of these compounds and the cellular response networks which they elicit. This information will be helpful to both improve our understanding of mode of action and help in the selection of appropriate mechanistic biomarkers, allowing us to progress the development of animal-free models with improved predictivity to the human situation.

COMPUTER-BASED PREDICTION OF TOXICITY USING THE ELECTRON-CONFORMATIONAL METHOD. APPLICATION TO FRAGRANCE ALLERGENS AND OTHER ENVIRONMENTAL POLLUTANTS

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Natalia N. Gorinchoy

2012-06-01

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.

Response of Bioluminescent Bacteria to Alkyltin Compounds.

Science.gov (United States)

1987-12-01

found in the butyltiri series of compounds; tributyltin was (’Stimes more toxic than dibutyltin and (- 50 times more toxic than (mono)butyltin. When...correlations between compounds, tributyltin was -35 tine more Kicrotxit and fish bLoessays for pure toxic than dibutyltin end -750 times More compounds and...the compounds as a decrease in toxicity (5) tributyltin compounds ea -150 tines more and a method to study synergistic andtoxic than trinethyltia

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

Science.gov (United States)

Kamimura, Hidetaka; Ito, Satoshi

2016-01-01

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.

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

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Kaludov Nikola

2011-09-01

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

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

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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.

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

NARCIS (Netherlands)

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

2009-01-01

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

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

NARCIS (Netherlands)

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

2009-01-01

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

Potent antifouling compounds produced by marine Streptomyces

KAUST Repository

Xu, Ying

2010-02-01

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.

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

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Saad Musbah Alasil

2014-01-01

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.

Toxic Compounds Analysis With High Performance Liquid Chromatography Detected By Electro Chemical Detector (Ecd)

OpenAIRE

Hideharu Shintaniq

2014-01-01

The principal area of application of high performance liquid chromatography-electrochemical detector (HPLC-ECD) has been in the analysis of naturally-occurring analytes, such as catecholamines, and pharmaceuticals in biological samples, HPLC-ECD has also applied to the analysis of pesticides and other analytes of interest to the toxicologist. In this paper, toxic area is described. In these, ammatoxins, aromatic amine, nitro-compounds, algal toxins, fungal toxins, pesticides, veterinary drug ...

Analysis of cell death inducing compounds

DEFF Research Database (Denmark)

Spicker, Jeppe; Pedersen, Henrik Toft; Nielsen, Henrik Bjørn

2007-01-01

Biomarkers for early detection of toxicity hold the promise of improving the failure rates in drug development. In the present study, gene expression levels were measured using full-genome RAE230 version 2 Affymetrix GeneChips on rat liver tissue 48 h after administration of six different compounds......), ornithine aminotransferase (OAT) and Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase) (Cyp2C29). RT-PCR for these three genes was performed and four additional compounds were included for validation. The quantitative RT-PCR analysis confirmed the findings based on the microarray data and using...... the three genes a classification rate of 55 of 57 samples was achieved for the classification of not toxic versus toxic. The single most promising biomarker (OAT) alone resulted in a surprisingly 100% correctly classified samples. OAT has not previously been linked to toxicity and cell death...

ToxAlerts: a Web server of structural alerts for toxic chemicals and compounds with potential adverse reactions.

Science.gov (United States)

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

2012-08-27

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, http://ochem.eu). 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 http://ochem.eu/alerts, and it is constantly

Where does the toxicity come from in saponin extract?

Science.gov (United States)

Jiang, Xiaogang; Cao, Yi; Jørgensen, Louise von Gersdorff; Strobel, Bjarne W; Hansen, Hans Chr Bruun; Cedergreen, Nina

2018-08-01

Saponin-rich plant extracts contain bioactive natural compounds and have many applications, e.g. as biopesticides and biosurfactants. The composition of saponin-rich plant extracts is very diverse, making environmental monitoring difficult. In this study various ecotoxicity data as well as exposure data have been collected to explore which compounds in the plant extract are relevant as plant protection agents and furthermore to clarify which compounds may cause undesired side-effects due to their toxicity. Hence, we quantified the toxicity of different fractions (saponins/non-saponins) in the plant extracts on the aquatic crustacean Daphnia magna and zebrafish (Danio rerio) embryos. In addition, we tested the toxicity changes during saponin degradation as well. The results confirm that saponins are responsible for the majority of toxicity (85.1-93.6%) of Quillaja saponaria extract. We, therefore, suggest saponins to be the main target of saponin-rich plant extracts, for instance in the saponin-based biopesticide regulation. Furthermore, we suggest that an abundant saponin fraction, QS-18 from Q. saponaria, can be a key monitoring target to represent the environmental concentration of the saponins, as it contributes with 26% and 61% of the joint toxicity to D. magna and D. rerio, respectively out of the total saponins. The degradation products of saponins are 3-7 times less toxic than the parent compound; therefore the focus should be mainly on the parent compounds. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Directory of Open Access Journals (Sweden)

William R. Schwan

2015-11-01

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.

Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells

International Nuclear Information System (INIS)

Dartel, Dorien A.M. van; Pennings, Jeroen L.A.; Schooten, Frederik J. van; Piersma, Aldert H.

2010-01-01

The embryonic stem cell test (EST) predicts developmental toxicity based on the inhibition of cardiomyocyte differentiation of embryonic stem cells (ESC). The subjective endpoint, the long culture duration together with the undefined applicability domain and related predictivity need further improvement to facilitate implementation of the EST into regulatory strategies. These aspects may be improved by studying gene expression changes in the ESC differentiation cultures and their modulation by compound exposure using transcriptomics. Here, we tested the developmental toxicants monobutyl phthalate and 6-aminonicotinamide. ESC were allowed to differentiated, and cardiomyocyte differentiation was assessed after 10 days of culture. RNA of solvent controls was collected after 0, 24, 48, 72 and 96 h of exposure, and RNA of developmental-toxicant-exposed cultures was collected after 24 and 96 h. Samples were hybridized to DNA microarrays, and 1355 genes were found differentially expressed among the unexposed experimental groups. These regulated genes were involved in differentiation-related processes, and Principal Component Analysis (PCA) based on these genes showed that the unexposed experimental groups appeared in chronological order in the PCA, which can therefore be regarded as a continuous representation of the differentiation track. The developmental-toxicant-exposed cultures appeared to deviate significantly from this differentiation track, which confirms the compound-modulating effects on the differentiation process. The incorporation of transcriptomics in the EST is expected to provide a more informative and improved endpoint in the EST as compared with morphology, allowing early detection of differentiation modulation. Furthermore, this approach may improve the definition of the applicability domain and predictivity of the EST.

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

Science.gov (United States)

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

2014-08-01

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

Assessing the Renal Toxicity of Capstone Depleted Uranium Oxides and Other Uranium Compounds

International Nuclear Information System (INIS)

Roszell, Laurie E.; Hahn, Fletcher; Lee, Robyn B.; Parkhurst, MaryAnn

2009-01-01

The primary target for uranium toxicity is the kidney. The most frequently used guideline for uranium kidney burdens is the International Commission on Radiation Protection (ICRP) value of 3 (micro)g U/g kidney, a value that is based largely upon chronic studies in animals. In the present effort, we have developed a risk model equation to assess potential outcomes of acute uranium exposure. Twenty-seven previously published case studies in which workers were acutely exposed to soluble compounds of uranium (as a result of workplace accidents) were analyzed. Kidney burdens of uranium for these individuals were determined based on uranium in the urine, and correlated with health effects observed over a period of up to 38 years. Based upon the severity of health effects, each individual was assigned a score (- to +++) and then placed into an Effect Group. A discriminant analysis was used to build a model equation to predict the Effect Group based on the amount of uranium in the kidneys. The model equation was able to predict the Effect Group with 85% accuracy. The risk model was used to predict the Effect Group for Soldiers exposed to DU as a result of friendly fire incidents during the 1991 Gulf War. This model equation can also be used to predict the Effect Group of new cases in which acute exposures to uranium have occurred

Assessing the toxic effects of ethylene glycol ethers using Quantitative Structure Toxicity Relationship models

International Nuclear Information System (INIS)

Ruiz, Patricia; Mumtaz, Moiz; Gombar, Vijay

2011-01-01

Experimental determination of toxicity profiles consumes a great deal of time, money, and other resources. Consequently, businesses, societies, and regulators strive for reliable alternatives such as Quantitative Structure Toxicity Relationship (QSTR) models to fill gaps in toxicity profiles of compounds of concern to human health. The use of glycol ethers and their health effects have recently attracted the attention of international organizations such as the World Health Organization (WHO). The board members of Concise International Chemical Assessment Documents (CICAD) recently identified inadequate testing as well as gaps in toxicity profiles of ethylene glycol mono-n-alkyl ethers (EGEs). The CICAD board requested the ATSDR Computational Toxicology and Methods Development Laboratory to conduct QSTR assessments of certain specific toxicity endpoints for these chemicals. In order to evaluate the potential health effects of EGEs, CICAD proposed a critical QSTR analysis of the mutagenicity, carcinogenicity, and developmental effects of EGEs and other selected chemicals. We report here results of the application of QSTRs to assess rodent carcinogenicity, mutagenicity, and developmental toxicity of four EGEs: 2-methoxyethanol, 2-ethoxyethanol, 2-propoxyethanol, and 2-butoxyethanol and their metabolites. Neither mutagenicity nor carcinogenicity is indicated for the parent compounds, but these compounds are predicted to be developmental toxicants. The predicted toxicity effects were subjected to reverse QSTR (rQSTR) analysis to identify structural attributes that may be the main drivers of the developmental toxicity potential of these compounds.

Toxicity identification evaluation methods for identification of toxicants in refinery effluents

International Nuclear Information System (INIS)

Barten, K.A.; Mount, D.R.; Hackett, J.R.

1993-01-01

During the last five years, the authors have used Toxicity Identification Evaluation (TIE) methods to characterize and identify the source(s) of toxicity in effluents from dozens of municipal and industrial facilities. In most cases, specific chemicals responsible for toxicity have been identified. Although generally successful, the initial experience was that for several refinery effluents, they were able only to qualitatively characterize the presence of organic toxicants; standard toxicant identification procedures were not able to isolate specific organic chemicals. They believe that organic toxicity in these refinery effluents is caused by multiple organic compounds rather than by just a few; evidence for this includes an inability to isolate toxicity in a small number of fractions using liquid chromatography and the presence of very large numbers of compounds in isolated fractions. There is also evidence that the toxicant(s) may be ionic, in that the toxicity of whole effluent and isolated fractions often show increasing toxicity with decreasing pH. Finally, positive-pressure filtration has also reduced toxicity in some samples. In this presentation the authors summarize their experiences with refinery effluents, focusing on typical patterns they have observed and alternative procedures they have used to better understand the nature of these toxicants

Survival of added bacterial species and metabolism of toxic compounds in natural environments

International Nuclear Information System (INIS)

King, V.M.

1987-01-01

Bacteria able to degrade either 2,4-dichlorophenol (DCP) or phenanthrene (PHEN) were isolated from polluted freshwater environments. Two isolates able to degrade each compound were tested for mineralization with a sensitive 14 C assay and for survival in lake water and sewage using a selective medium. One DCP isolate was identified as Alcaligenes paradoxus and the other as Alcaligenes sp. One PHEN isolate was identified as Pseudomonas fluorescens and the other as Pseudomonas sp. All four isolates survived and grew in sterile environments which indicated that starvation would not be a factor in survival of these strains. The number of organisms declined immediately in number in nonsterile lake water. However, they did survive or even grow in nonsterile sewage for a short period before declining in number. Biotic factors appeared to be influential for survival and mineralization of target compounds in many environments. The removal of protozoa, which prey on bacteria, improved survival of the added cells, but had no influence on the mineralization of 10 μg DCP/L. In comparison, degradation of 10 and 25 mg DCP/L stopped after a few days. Yeast nitrogen base appeared to overcome the lack of nutrient regeneration, a function attributed to protozoa. The additional nutrients increased toxicant mineralization, especially when seeded with appropriate species. Thus, protozoa may limit growth of added cells but appear to be needed for mineralization of higher concentrations of DCP

Release behavior and toxicity profiles towards A549 cell lines of ciprofloxacin from its layered zinc hydroxide intercalation compound.

Science.gov (United States)

Abdul Latip, Ahmad Faiz; Hussein, Mohd Zobir; Stanslas, Johnson; Wong, Charng Choon; Adnan, Rohana

2013-01-01

Layered hydroxides salts (LHS), a layered inorganic compound is gaining attention in a wide range of applications, particularly due to its unique anion exchange properties. In this work, layered zinc hydroxide nitrate (LZH), a family member of LHS was intercalated with anionic ciprofloxacin (CFX), a broad spectrum antibiotic via ion exchange in a mixture solution of water:ethanol. Powder x-ray diffraction (XRD), Fourier transform infrared (FTIR) and thermogravimetric analysis (TGA) confirmed the drug anions were successfully intercalated in the interlayer space of LZH. Specific surface area of the obtained compound was increased compared to that of the host due to the different pore textures between the two materials. CFX anions were slowly released over 80 hours in phosphate-buffered saline (PBS) solution due to strong interactions that occurred between the intercalated anions and the host lattices. The intercalation compound demonstrated enhanced antiproliferative effects towards A549 cancer cells compared to the toxicity of CFX alone. Strong host-guest interactions between the LZH lattice and the CFX anion give rise to a new intercalation compound that demonstrates sustained release mode and enhanced toxicity effects towards A549 cell lines. These findings should serve as foundations towards further developments of the brucite-like host material in drug delivery systems.

Rapid Assessment of the Toxicity of Fungal Compounds Using Luminescent Vibrio qinghaiensis sp. Q67

Directory of Open Access Journals (Sweden)

Qijie Jian

2017-10-01

Full Text Available Most tropical fruits after harvest are very perishable because of fungal infection. Since some pathogenic fungi can produce hazardous compounds such as mycotoxins, novel rapid and effective methods to assess those hazardous compounds are urgently needed. Herein we report that Vibrio qinghaiensis sp. Q67, a luminescent bacterium, can be used to rapidly assess the toxicities of mycotoxins and cultures from mycotoxin-producing pathogens. A good correlation (R2 > 0.98 between concentrations of the mycotoxins (fumonisin B1, deoxynivalenol, zearalenone, ochratoxin A, patulin, and citrinin and the luminous intensity of V. qinghaiensis sp. Q67 was obtained. Furthermore, significant correlations (R2 > 0.96 between the amount of mycotoxin and the luminous intensity from the cultures of 10 major mycotoxin-producing pathogens were also observed. In addition, Fusarium proliferatum (half-maximal inhibitory concentration (IC50 = 17.49% exhibited greater luminescence suppression than Fusarium semitectum (IC50 = 92.56% or Fusarium oxysporum (IC50 = 28.61%, which was in agreement with the existing higher levels of fumonisin B1, fumonisin B2, and deoxynivalenol, which were measured by high-performance liquid chromatography-tandem mass spectrometry. These results suggest that V. qinghaiensis sp. Q67 is a promising alternative for the rapid evaluation of the toxicity of fungal mycotoxins.

Heterocyclic Schiff bases as non toxic antioxidants: Solvent effect, structure activity relationship and mechanism of action

Science.gov (United States)

Shanty, Angamaly Antony; Mohanan, Puzhavoorparambil Velayudhan

2018-03-01

Phenolic heterocyclic imine based Schiff bases from Thiophene-2-carboxaldehyde and Pyrrole-2-carboxaldehyde were synthesized and characterized as novel antioxidants. The solvent effects of these Schiff bases were determined and compared with standard antioxidants, BHA employing DPPH assay and ABTS assay. Fixed reaction time and Steady state measurement were used for study. IC50 and EC50 were calculated. Structure-activity relationship revealed that the electron donating group in the phenolic ring increases the activity where as the electron withdrawing moiety decreases the activity. The Schiff base derivatives showed antioxidant property by two different pathways namely SPLET and HAT mechanisms in DPPH assay. While in ABTS method, the reaction between ABTS radical and Schiff bases involves electron transfer followed by proton transfer (ET-PT) mechanism. The cytotoxicity of these compounds has been evaluated by MTT assay. The results showed that all these compounds are non toxic in nature.

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

Science.gov (United States)

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

2014-07-01

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

In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

Science.gov (United States)

Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

2015-01-01

The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

Toxicity of Single and Mixed Contaminants in Seawater Measured with Acute Toxicity Bioassays

Directory of Open Access Journals (Sweden)

A.R. Fernandez-Alba

2002-01-01

Full Text Available Different types of organic pollutants commonly detected in seawater have been evaluated by acute toxicity bioassays. Vibrio fischeri, Daphnia magna, and Selenastrum capricornotum were selected to test toxic effects of individual compounds and mixtures of these compounds, obtaining EC50 values in the range of 0.001 to 28.9 mg/l. In the case of mixtures, synergistic toxic responses were seen for a clear majority of the cases (>60%. Mixtures containing methyl-tertiary-butyl ether (MTBE exhibit accelerated processes that result in a change in concentration required to produce a toxic effect; for example, in the case of mixtures containing MTBE and Diuron and Dichlofluanid.

Uranium-oxide-based catalysts for the destruction of volatile chloro-organic compounds

International Nuclear Information System (INIS)

Hutchings, G.; Heneghan, C.S.; Taylor, S.H.

1996-01-01

The industrial release of hydrocarbons and chlorine-containing organic molecules into the environment continues to attract considerable public concern, which in turn has led to governmental attempts to control such emissions. The challenge is to reduce pollution without stifling economic growth. Chlorine-containing pollutants are known to be particularly stable, and at present the main industrial process for their destruction involves thermal oxidation at 1,000 o C, an expensive process that can lead to the formation of highly toxic by-products such as dioxins and dibenzofurans. Catalytic combustion at lower temperatures could potentially destroy pollutants more efficiently (in terms of energy requirements) and without forming toxic by-products. Current industrial catalysts are based on precious metals that are deactivated rapidly by organochlorine compounds. Here we report that catalysts based on uranium oxide efficiently destroy a range of hydrocarbon and chlorine-containing pollutants, and that these catalysts are resistant to deactivation. We show that benzene, toluene, chlorobutane and chlorobenzene can be destroyed at moderate temperatures ( o C) and industrially relevant flow rates. (Author)

Acute Toxicity (LC50 96 Hours of Organophosphate Pesticide With Poksim Active Compound And Haematology And Histopathology Review Goldfish (Cyprinus carpio L

Directory of Open Access Journals (Sweden)

Dewi Nur Setyorini

2015-04-01

Full Text Available This research has the objectives to determine LC50 96 hours value and observation toward hematology, gills and kidney histology of goldfish (Cyprinus carpio exposed to organophosphate pesticide with Poksim active compound (trade brand FOKKER 500 EC. Method used in this paper is experiment to determine LC50 96 hour value with probit analysis. Descriptive method was used for gills and kidney tissues microanatomy observation with hematoxilin eosin (HE coloring and hematology. Toxicity result of Fokker 500 EC pesticide toward goldfish obtained LC50 96 hours with 41,7 ppm. Histological result showed that increasing exposure doses in real test had caused increase gills and kidney tissues damage. Hematology observation result during research obtained that along with the increasing exposure doses of pesticide in the real test, acute toxicity test would caused reduction in total erythrocyte, leukocyte and hemoglobin of goldfish. Result also showed that Fokker pesticide usage was allowed until 1,8 ppm dose based on histology and hematology evaluation. Keywords: acute toxicity, goldfish, histology, hematology, pesticide

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

International Nuclear Information System (INIS)

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

1993-01-01

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

Oxidative stress in chemical toxicity

Energy Technology Data Exchange (ETDEWEB)

Kappus, H.

1986-05-01

The toxic effect of compounds which undergo redox cycling enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.

Organophosphorus insecticides: Toxic effects and bioanalytical tests for evaluating toxicity during degradation processes

Directory of Open Access Journals (Sweden)

Čolović Mirjana B.

2013-01-01

Full Text Available Organophosphorus insecticides have been the most applied group of insecticides for the last two decades. Their main toxic effects are related to irreversible inactivation of acetylcholinesterase (AChE. Actually, they covalently bind to serine OH group in the enzyme active site forming phosphorylated enzyme that cannot hydrolyze acetylcholine. Organophosphorus insecticides in the environment undergo the natural degradation pathway including mainly homogeneous and heterogeneous hydrolysis (especially at high pH generating non-inhibiting products. Additionally, thio organophosphates are easily oxidized by naturally present oxidants and UV light, forming more toxic and stable oxons. Thus, oxidative degradation procedures, generally referred as advanced oxidation processes (AOP, have been applied for their efficient removal from contaminated waters. The most applied bioassays to monitor the organophosphate toxicity i.e. the detoxification degree during AOP are Vibrio fischeri and AChE bioassays. Vibrio fischeri toxicity test exploits bioluminescence as the measure of luciferase activity of this marine bacterium, whereas AChE bioassay is based on AChE activity inhibition. Both bioanalytical techniques are rapid (several minutes, simple, sensitive and reproducible. Vibrio fischeri test seems to be a versatile indicator of toxic compounds generated in AOP for organophosphorus insecticides degradation. However, detection of neurotoxic AChE inhibitors, which can be formed in AOP of some organophosphates, requires AChE bioassays. Therefore, AChE toxicity test is more appropriate for monitoring the degradation processes of thio organophosphates, because more toxic oxo organophosphates might be formed and overlooked by Vibrio fischeri bioluminescence inhibition. In addition, during organophosphates removal by AOP, compounds with strong genotoxic potential may be formed, which cannot be detected by standard toxicity tests. For this reason, determination of

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: Max.Costa@nyumc.org

2012-04-01

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.

The Study of Compound Quality of various Siam Weed (Eupatorium odoratum) Extracts and Toxicity Detoxification mechanisms Against 3rd Instar Larvae of Fruit Fly (Dacus dorsalis)

International Nuclear Information System (INIS)

Sutthivaiyakit, Pakawadee; Visetson, Suraphon; Sutthivaiyakit, Somyote; Patharakorn, Thipamon; Patharakorn, Surapol; Piadang, Patharakorn

2006-09-01

The 1H-NMR spectroscopy showed signals of DeltaH tild0.71.6 from hexane-leaf extracts from Siam weed (Eupatorium odoratum) These signals derive from protons of non-polar compounds which include fatty acid residues and terpinoids. In addition, the amplification of the signals indicated of some minor DeltaH tild6.2-7.7. This revealed protons from aromatic rings possibly involving in flavonoids from 1H-NMR spectrum. This is a believe that is a believe that these compounds could be varied from slightly polar compounds to moderately polar compounds. Furthermore, the Thin Layer Chromatography (TLC) of hexane, chloroform and methanol fractions showed the extracts composed of majority of less polar. It is and indication of the method of separation is quite food for separation of polarity basis from these extracts. Finally, the TLC of hexane fraction distinctively produced 7-8 compounds from the extracts. Toxicity testing using topical spray method showed that methnoloc extracts gave highest toxicity against 3rd instar larvae of fruit fly (Darcus dorsalis). The root extracts produced ca. 5 fold mohile GSH-S-transferase ws elevated 2-3 fold. The addition of dimethyl maleate into the extraccts increased their toxicity. The persistent experiment of eupathal from the extracts showed that the extracts can be stabilixed under aqueous solution upto 1 month with losing the compound. Finally, the Siam weed extracts prosuced non toxic to non-target organisms such as gabbies, bee, and mouse. The results of LC50 showed 15,000-26,000 mg/L 6,000-15,000 mg/L and 3,000-10,000 mg/L from hexane, chloroform and methanol extracts, respectively.

Fluorescent Chemosensors for Toxic Organophosphorus Pesticides: A Review

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Kenneth Fletcher

2010-07-01

Full Text Available Many organophosphorus (OP based compounds are highly toxic and powerful inhibitors of cholinesterases that generate serious environmental and human health concerns. Organothiophosphates with a thiophosphoryl (P=S functional group constitute a broad class of these widely used pesticides. They are related to the more reactive phosphoryl (P=O organophosphates, which include very lethal nerve agents and chemical warfare agents, such as, VX, Soman and Sarin. Unfortunately, widespread and frequent commercial use of OP-based compounds in agricultural lands has resulted in their presence as residues in crops, livestock, and poultry products and also led to their migration into aquifers. Thus, the design of new sensors with improved analyte selectivity and sensitivity is of paramount importance in this area. Herein, we review recent advances in the development of fluorescent chemosensors for toxic OP pesticides and related compounds. We also discuss challenges and progress towards the design of future chemosensors with dual modes for signal transduction.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

Energy Technology Data Exchange (ETDEWEB)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

2011-12-15

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Biodegradable alternative for removing toxic compounds from sugarcane bagasse hemicellulosic hydrolysates for valorization in biorefineries.

Science.gov (United States)

Silva-Fernandes, T; Santos, J C; Hasmann, F; Rodrigues, R C L B; Izario Filho, H J; Felipe, M G A

2017-11-01

Among the major challenges for hemicellulosic hydrolysate application in fermentative processes, there is the presence of toxic compounds generated during the pretreatment of the biomass, which can inhibit microbial growth. Therefore, the development of efficient, biodegradable and cost-effective detoxification methods for lignocellulosic hydrolysates is crucial. In this work, two tannin-based biopolymers (called A and B) were tested in the detoxification of sugarcane bagasse hydrolysate for subsequent fermentation by Candida guilliermondii. The effects of biopolymer concentration, pH, temperature, and contact time were studied using a 2 4 experimental design for both biopolymers. Results revealed that the biopolymer concentration and the pH were the most significant factors in the detoxification step. Biopolymer A removed phenolics, 5-hydroxymethylfurfural, and nickel from the hydrolysate more efficiently than biopolymer B, while biopolymer B was efficient to remove chromium at 15% (v/v). Detoxification enhanced the fermentation of sugarcane bagasse hydrolysate, and the biopolymers showed different influences on the process. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quinoline-Based Hybrid Compounds with Antimalarial Activity

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Xhamla Nqoro

2017-12-01

Full Text Available The application of quinoline-based compounds for the treatment of malaria infections is hampered by drug resistance. Drug resistance has led to the combination of quinolines with other classes of antimalarials resulting in enhanced therapeutic outcomes. However, the combination of antimalarials is limited by drug-drug interactions. In order to overcome the aforementioned factors, several researchers have reported hybrid compounds prepared by reacting quinoline-based compounds with other compounds via selected functionalities. This review will focus on the currently reported quinoline-based hybrid compounds and their preclinical studies.

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

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Wen-Tien Tsai

2016-09-01

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.

THE 2005 WORLD HEALTH ORGANIZATION RE-EVALUATION OF HUMAN AND MAMMALIAN TOXIC EQUIVALENCY FACTORS FOR DIOXINS AND DIOXIN-LIKE COMPOUNDS

Science.gov (United States)

In June 2005 a WHO-IPCS expert meeting was held in Geneva during which the toxic equivalency factors (TEFs) for dioxin like compounds, including some polychlorinated biphenyls (PCBs), were re-evaluated. For this re-evaluation process the refined TEF database recently published by...

Developmental toxicity assessment of common excipients using a stem cell-based in vitro morphogenesis model.

Science.gov (United States)

Yuan, Chloe J; Marikawa, Yusuke

2017-11-01

Various chemical compounds can inflict developmental toxicity when sufficiently high concentrations are exposed to embryos at the critical stages of development. Excipients, such as coloring agents and preservatives, are pharmacologically inactive ingredients that are included in various medications, foods, and cosmetics. However, concentrations that may adversely affect embryo development are largely unknown for most excipients. Here, the lowest observed adverse effect level (LOAEL) to inflict developmental toxicity was assessed for three coloring agents (allura red, brilliant blue, and tartrazine) and three preservatives (butylated hydroxyanisole, metabisulfite, and methylparaben). Adverse impact of a compound exposure was determined using the stem cell-based in vitro morphogenesis model, in which three-dimensional cell aggregates, or embryoid bodies (EBs), recapitulate embryonic processes of body axis elongation and patterning. LOAEL to impair EB morphogenesis was 200 μM for methylparaben, 400 μM for butylated hydroxyanisole, 600 μM for allura red and brilliant blue, and 1000 μM for metabisulfite. Gene expression analyses of excipient-treated EBs revealed that butylated hydroxyanisole and methylparaben significantly altered profiles of developmental regulators involved in axial elongation and patterning of the body. The present study may provide a novel in vitro approach to investigate potential developmental toxicity of common excipients with mechanistic insights. Copyright © 2017 Elsevier Ltd. All rights reserved.

Predicting the aquatic toxicity mode of action using logistic regression and linear discriminant analysis.

Science.gov (United States)

Ren, Y Y; Zhou, L C; Yang, L; Liu, P Y; Zhao, B W; Liu, H X

2016-09-01

The paper highlights the use of the logistic regression (LR) method in the construction of acceptable statistically significant, robust and predictive models for the classification of chemicals according to their aquatic toxic modes of action. Essentials accounting for a reliable model were all considered carefully. The model predictors were selected by stepwise forward discriminant analysis (LDA) from a combined pool of experimental data and chemical structure-based descriptors calculated by the CODESSA and DRAGON software packages. Model predictive ability was validated both internally and externally. The applicability domain was checked by the leverage approach to verify prediction reliability. The obtained models are simple and easy to interpret. In general, LR performs much better than LDA and seems to be more attractive for the prediction of the more toxic compounds, i.e. compounds that exhibit excess toxicity versus non-polar narcotic compounds and more reactive compounds versus less reactive compounds. In addition, model fit and regression diagnostics was done through the influence plot which reflects the hat-values, studentized residuals, and Cook's distance statistics of each sample. Overdispersion was also checked for the LR model. The relationships between the descriptors and the aquatic toxic behaviour of compounds are also discussed.

Dietary compounds as modulators of metals and metalloids toxicity.

Science.gov (United States)

Jadán-Piedra, Carlos; Chiocchetti, Gabriela Matuoka; Clemente, María Jesús; Vélez, Dinoraz; Devesa, Vicenta

2017-07-07

A large part of the population is exposed to metals and metalloids through the diet. Most of the in vivo studies on its toxicokinetics and toxicity are conducted by means of exposure through drinking water or by intragastric or intraperitoneal administration of aqueous standards, and therefore they do not consider the effect of the food matrix on the exposure. Numerous studies show that some components of the diet can modulate the toxicity of these food contaminants, reducing their effect on a systemic level. Part of this protective role may be due to a reduction of intestinal absorption and subsequent tissue accumulation of the toxic element, although it may also be a consequence of their ability to counteract the toxicity directly by their antioxidant and/or anti-inflammatory activity, among other factors. The present review provides a compilation of existing information about the effect that certain components of the diet have on the toxicokinetics and toxicity of the metals and metalloids of greatest toxicological importance that are present in food (arsenic, cadmium, lead, and mercury), and of their most toxic chemical species.

Studies on the toxic interaction between monensin and tiamulin in rats: toxicity and pathology.

Science.gov (United States)

Szücs, G; Bajnógel, J; Varga, A; Móra, Z; Laczay, P

2000-01-01

The characteristics of the toxic interaction between monensin and tiamulin were investigated in rats. A three-day comparative oral repeated-dose toxicity study was performed in Phase I, when the effects of monensin and tiamulin were studied separately (monensin 10, 30, and 50 mg/kg or tiamulin 40, 120, and 200 mg/kg body weight, respectively). In Phase II, the two compounds were administered simultaneously to study the toxic interaction (monensin 10 mg/kg and tiamulin 40 mg/kg b.w., respectively). Monensin proved to be toxic to rats at doses of 30 and 50 mg/kg. Tiamulin was well tolerated up to the dose of 200 mg/kg. After combined administration, signs of toxicity were seen (including lethality in females). Monensin caused a dose-dependent cardiotoxic effect and vacuolar degeneration of the skeletal muscles in the animals given 50 mg/kg. Both compounds exerted a toxic effect on the liver in high doses. After simultaneous administration of the two compounds, there was a mild effect on the liver (females only), hydropic degeneration of the myocardium and vacuolar degeneration of the skeletal muscles. The alteration seen in the skeletal muscles was more marked than that seen after the administration of 50 mg/kg monensin alone.

Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

International Nuclear Information System (INIS)

McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A.; Alaee, Mehran; Simpson, Andre J.; Simpson, Myrna J.

2011-01-01

Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: → NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. → Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. → NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - 1 H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

Identification of toxic cyclopeptides based on mass spectral library matching

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Boris L. Milman

2014-08-01

Full Text Available To gain perspective on the use of tandem mass spectral libraries for identification of toxic cyclic peptides, the new library was built from 263 mass spectra (mainly MS2 spectra of 59 compounds of that group, such as microcystins, amatoxins, and some related compounds. Mass spectra were extracted from the literature or specially acquired on ESI-Q-ToF and MALDI-ToF/ToF tandem instruments. ESI-MS2 product-ion mass spectra appeared to be rather close to MALDI-ToF/ToF fragment spectra which are uncommon for mass spectral libraries. Testing of the library was based on searches where reference spectra were in turn cross-compared. The percentage of 1st rank correct identifications (true positives was 70% in a general case and 88–91% without including knowingly defective (‘one-dimension’ spectra as test ones. The percentage of 88–91% is the principal estimate for the overall performance of this library that can be used in a method of choice for identification of individual cyclopeptides and also for group recognition of individual classes of such peptides. The approach to identification of cyclopeptides based on mass spectral library matching proved to be the most effective for abundant toxins. That was confirmed by analysis of extracts from two cyanobacterial strains.

radiochemical studies on the binding of humic materials with toxic elements and compounds

International Nuclear Information System (INIS)

Afifi, D.M.I.

2001-01-01

industrial nations produce several billion tons of waste every year . this figure will increase as both population and industrial growth increase. there are many kinds of waste, including refinery waste, which consists of hydrocarbons, heavy metals, metal catalysts and caustic solution; dredge spoils, some of which are highly polluted and cntains substances potentially hazardous to human health or the marine ecosystem; chemical waste such as insecticides, pesticides, other complex chemicals and heavy metals; radioactive waste and agricultural waste, anmd most of them are extremely hazardous and harmful to the marine ecosystem and its inhabitants.the aim of this thesis is to study the binding of humic materials with toxic elements and compounds

Research strategies for design and development of NSAIDs: clue to balance potency and toxicity of acetanilide compounds.

Science.gov (United States)

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

2001-08-01

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.

Effects of toxic compounds in Montipora capitata on exogenous and endogenous zooxanthellae performance and fertilization success.

Directory of Open Access Journals (Sweden)

Mary Hagedorn

Full Text Available Studies have identified chemicals within the stony coral genus Montipora that have significant biological activities. For example, Montiporic acids A and B and other compounds have been isolated from the adult tissue and eggs of Montipora spp. and have displayed antimicrobial activity and cytotoxicity in cultured cells. The ecological role of these toxic compounds is currently unclear. This study examines the role these toxins play in reproduction. Toxins were found in the eggs and larvae of the coral Montipora capitata. Releasing these toxins by crushing both the eggs and larvae resulted in irreversible inhibition of photosynthesis in endogenous and exogenous zooxanthellae within minutes. Moreover, these toxins were stable, as frozen storage of eggs and larvae did not affect toxicity. Photosynthetic competency of Porites compressa zooxanthellae treated with either frozen or fresh, crushed eggs was inhibited similarly (P > 0.05, ANCOVA. Addition of toxic eggs plugs to live P. compressa fragments caused complete tissue necrosis under the exposed area on the fragments within 1 week. Small volumes of M. capitata crushed eggs added to sperm suspensions reduced in vitro fertilization success by killing the sperm. After 30 min, untreated sperm maintained 90 ± 1.9% SEM motility while those treated with crushed eggs were rendered immotile, 4 ± 1.4% SEM. Flow cytometry indicated membrane disruption of the immotile sperm. Fertilization success using untreated sperm was 79 ± 4% SEM, whereas the success rate dropped significantly after exposure to the crushed eggs, 1.3 ± 0% SEM. Unlike the eggs and the larvae, M. capitata sperm did not reduce the photosynthetic competency of P. compressa zooxanthellae, suggesting the sperm was nontoxic. The identity of the toxins, cellular mechanism of action, advantage of the toxins for M. capitata and their role on the reef are still unknown.

Effects of toxic compounds in Montipora capitata on exogenous and endogenous zooxanthellae performance and fertilization success.

Science.gov (United States)

Hagedorn, Mary; Farrell, Ann; Carter, Virginia; Zuchowicz, Nikolas; Johnston, Erika; Padilla-Gamiño, Jacqueline; Gunasekera, Sarath; Paul, Valerie

2015-01-01

Studies have identified chemicals within the stony coral genus Montipora that have significant biological activities. For example, Montiporic acids A and B and other compounds have been isolated from the adult tissue and eggs of Montipora spp. and have displayed antimicrobial activity and cytotoxicity in cultured cells. The ecological role of these toxic compounds is currently unclear. This study examines the role these toxins play in reproduction. Toxins were found in the eggs and larvae of the coral Montipora capitata. Releasing these toxins by crushing both the eggs and larvae resulted in irreversible inhibition of photosynthesis in endogenous and exogenous zooxanthellae within minutes. Moreover, these toxins were stable, as frozen storage of eggs and larvae did not affect toxicity. Photosynthetic competency of Porites compressa zooxanthellae treated with either frozen or fresh, crushed eggs was inhibited similarly (P > 0.05, ANCOVA). Addition of toxic eggs plugs to live P. compressa fragments caused complete tissue necrosis under the exposed area on the fragments within 1 week. Small volumes of M. capitata crushed eggs added to sperm suspensions reduced in vitro fertilization success by killing the sperm. After 30 min, untreated sperm maintained 90 ± 1.9% SEM motility while those treated with crushed eggs were rendered immotile, 4 ± 1.4% SEM. Flow cytometry indicated membrane disruption of the immotile sperm. Fertilization success using untreated sperm was 79 ± 4% SEM, whereas the success rate dropped significantly after exposure to the crushed eggs, 1.3 ± 0% SEM. Unlike the eggs and the larvae, M. capitata sperm did not reduce the photosynthetic competency of P. compressa zooxanthellae, suggesting the sperm was nontoxic. The identity of the toxins, cellular mechanism of action, advantage of the toxins for M. capitata and their role on the reef are still unknown.

Acute methaemoglobinaemia initially treated as organophosphate poisoning leading to atropine toxicity.

Science.gov (United States)

Kakhandki, Srinivas; Yahya, Mohammed; Praveen, Mudalgi

2012-07-01

A case of unknown compound poisoning is presented. It was initially treated as organophosphate poisoning with lack of response. A timely diagnosis of acute methaemoglobinaemia and iatrogenic atropine toxicity was made based on clinical evaluation. Treatment of methaemoglobinaemia using oral methylene blue and of atropine toxicity with supportive measures could save the patient.

A three-stage-integrative approach for the identification of potential hepatotoxic compounds from botanical products.

Science.gov (United States)

Jin, Yecheng; Zhao, Xiaoping; Zhang, Yufeng; Li, Xiang; Nie, Xiaojing; Wang, Yi; Fan, Xiaohui

2011-05-01

With the increasing use of herbal medicines and dietary supplements, intensive concerns about their potential toxicities have been raised. Screening and identifying the toxic compounds from these botanical products composed by hundreds of components have become a critical but challenging problem. In this study, 3 methods, including fraction separation, an in-house-developed fluorescein diacetate-based automatic microscopy screening (FAMS) platform, and liquid chromatography-mass spectrometry-based compounds identification were integrated within the Three-Stage-Integrative (TSI) approach for the identification of potential hepatotoxicants from botanical products. The sensitivity and linear range of FAMS assay was validated and compared with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay by previously reported hepatotoxic compounds. The success of TSI approach was further demonstrated by its application to Fructus aristolochiae. Aristolochic acid IVa and aristolodione were tentatively identified to be potential hepatotoxicants in this plant. These applications suggested that our TSI approach provides an effective tool for identifying potential toxic compounds from botanical products.

Specificity of carboxylesterase protection against the toxicity of organophosphorus compounds. (Reannouncement with new availability information)

Energy Technology Data Exchange (ETDEWEB)

Maxwell, D.M.

1992-12-31

The ability of endogenous carboxylesterase (CaE) to protect against the lethal effects of a variety of organophosphorus (OP) compounds was examined in rats. The in vivo protection provided by endogenous CaE was measured by the difference in the LD50 values of OP compounds in controlrats and rats whose CaE activity had been inhibited by sc injection with2 mg/kg of 2-(O cresyl)-4H-1,3,2-benzodi oxaphosphorin-2-oxide. Endogenous CaE provided significant protection against the in vivo toxicity of soman, sarin, tabun, and paraoxon, but not against dichlorvos, diisopropyl fluorophosphate, or ethoxymethyl-S-2- (DIISOPROPYLAMINO)ETHYL THIOPHOSPHONATE (VX). The relationship between the in vivo CaE protection against OP compounds and their relative reactivities with CaE and acetylcholinesterase (AChE) was evaluated by measuring the in vitro bimolecular rate constants (ki) for inhibition of plasma CaE and brain AChE. Except for VX, ki values for CaE inhibition varied <10-fold while ki values for AChE inhibition varied 105-fold. Chemical warfare agents, Nerve agents, Organophosphoruscompound soman, VX, Carboxylesterase, Protection, Pretreatment.

TiO2–AgCl Based Nanoparticles for Photocatalytic Production of Phenolic Compounds from Lignocellulosic Residues

DEFF Research Database (Denmark)

Tsapekos, Panagiotis; Alvarado-Morales, Merlin; Boscaro, Davide

2018-01-01

Lignocellulosic biomass residues can be used as an interesting resource for the production of biochemicals or sustainable fuels. In this optic, lignin represents an interesting raw material for the production of chemicals, such as aromatic compounds, or fuels. This can contribute in moving away...... for optimal phenolic compounds production. It was found that the photocatalytic treatment boosted the phenolic production from wheat straw. The efficiency of the process depended on the initial pH and catalyst concentration. Process optimization towards increased phenolic compounds production was performed...... of toxic compounds presented in the catalyst-straw solution and specifically, HNO3 was toxic to methanogenic communities. Hence, to succeed in an efficient biorefinery framework where total phenols and biogas production are combined, the usage of HNO3 for catalyst synthesis should be avoided....

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

Science.gov (United States)

Medina Juárez, L A; Trejo González, A

1989-12-01

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.

Toxicities of emamectin benzoate homologues and photodegradates to Lepidoptera.

Science.gov (United States)

Argentine, Joseph A; Jansson, Richard K; Starner, Van R; Halliday, W Ross

2002-12-01

The toxicity of a number of emamectin benzoate homologues and photodegradates to five species of Lepidoptera was investigated using diet and foliar bioassays. The emamectin benzoate homologues B1a and B1b were equally toxic in the diet and foliar assays to Spodoptera exigua (Hübner), Heliothis virescens (F.), Tricoplusia ni (Hübner), and Spodoptera frugiperda (J. E. Smith), within each of these species. Plutella xylostella (L.) was the most sensitive species to emamectin benzoate. The AB1a photodegradate of emamectin benzoate was as toxic as the parent compound in the diet assay. However, in the foliage assay AB1a was 4.4-fold less toxic to S. exigua than the parent compound. The MFB1a photodegradate of emamectin benzoate was as toxic as the parent compound to P. xylostella, and 3.1 to 6.2 times as toxic as the parent compound to the other species in the diet assay. The order of toxicity of the photodegradates were AB1a > MFB1a > FAB1a > 8,9-Z-MAB1a > PAB1a.

Toxicology of perfluorinated compounds

Energy Technology Data Exchange (ETDEWEB)

Stahl, Thorsten [Hessian State Laboratory, Wiesbaden (Germany); Mattern, Daniela; Brunn, Hubertus [Hessian State Laboratory, Giessen (Germany)

2011-12-15

Perfluorinated compounds [PFCs] have found a wide use in industrial products and processes and in a vast array of consumer products. PFCs are molecules made up of carbon chains to which fluorine atoms are bound. Due to the strength of the carbon/fluorine bond, the molecules are chemically very stable and are highly resistant to biological degradation; therefore, they belong to a class of compounds that tend to persist in the environment. These compounds can bioaccumulate and also undergo biomagnification. Within the class of PFC chemicals, perfluorooctanoic acid and perfluorosulphonic acid are generally considered reference substances. Meanwhile, PFCs can be detected almost ubiquitously, e.g., in water, plants, different kinds of foodstuffs, in animals such as fish, birds, in mammals, as well as in human breast milk and blood. PFCs are proposed as a new class of 'persistent organic pollutants'. Numerous publications allude to the negative effects of PFCs on human health. The following review describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity including carcinogenesis, genotoxicity and epigenetic effects, reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies on perfluorinated compounds). (orig.)

Addressing the selectivity and toxicity of antiviral nucleosides.

Science.gov (United States)

Feng, Joy Y

2018-01-01

Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.

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

Science.gov (United States)

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

2017-07-03

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: http://limtox.bioinfo.cnio.es. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

Directory of Open Access Journals (Sweden)

Nicolas Defarge

2016-02-01

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.

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

Directory of Open Access Journals (Sweden)

Farzamfar B

2008-04-01

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

Yellow phosphorus process to convert toxic chemicals to non-toxic products

Science.gov (United States)

Chang, S.G.

1994-07-26

The present invention relates to a process for generating reactive species for destroying toxic chemicals. This process first contacts air or oxygen with aqueous emulsions of molten yellow phosphorus. This contact results in rapid production of abundant reactive species such as O, O[sub 3], PO, PO[sub 2], etc. A gaseous or liquid aqueous solution organic or inorganic chemicals is next contacted by these reactive species to reduce the concentration of toxic chemical and result in a non-toxic product. The final oxidation product of yellow phosphorus is phosphoric acid of a quality which can be recovered for commercial use. A process is developed such that the byproduct, phosphoric acid, is obtained without contamination of toxic species in liquids treated. A gas stream containing ozone without contamination of phosphorus containing species is also obtained in a simple and cost-effective manner. This process is demonstrated to be effective for destroying many types of toxic organic, or inorganic, compounds, including polychlorinated biphenyls (PCB), aromatic chlorides, amines, alcohols, acids, nitro aromatics, aliphatic chlorides, polynuclear aromatic compounds (PAH), dyes, pesticides, sulfides, hydroxyamines, ureas, dithionates and the like. 20 figs.

Using quantitative structure-activity relationships (QSAR) to predict toxic endpoints for polycyclic aromatic hydrocarbons (PAH).

Science.gov (United States)

Bruce, Erica D; Autenrieth, Robin L; Burghardt, Robert C; Donnelly, K C; McDonald, Thomas J

2008-01-01

Quantitative structure-activity relationships (QSAR) offer a reliable, cost-effective alternative to the time, money, and animal lives necessary to determine chemical toxicity by traditional methods. Additionally, humans are exposed to tens of thousands of chemicals in their lifetimes, necessitating the determination of chemical toxicity and screening for those posing the greatest risk to human health. This study developed models to predict toxic endpoints for three bioassays specific to several stages of carcinogenesis. The ethoxyresorufin O-deethylase assay (EROD), the Salmonella/microsome assay, and a gap junction intercellular communication (GJIC) assay were chosen for their ability to measure toxic endpoints specific to activation-, induction-, and promotion-related effects of polycyclic aromatic hydrocarbons (PAH). Shape-electronic, spatial, information content, and topological descriptors proved to be important descriptors in predicting the toxicity of PAH in these bioassays. Bioassay-based toxic equivalency factors (TEF(B)) were developed for several PAH using the quantitative structure-toxicity relationships (QSTR) developed. Predicting toxicity for a specific PAH compound, such as a bioassay-based potential potency (PP(B)) or a TEF(B), is possible by combining the predicted behavior from the QSTR models. These toxicity estimates may then be incorporated into a risk assessment for compounds that lack toxicity data. Accurate toxicity predictions are made by examining each type of endpoint important to the process of carcinogenicity, and a clearer understanding between composition and toxicity can be obtained.

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

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Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

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

Evaluation of toxic and interactive toxic effects of three agrochemicals and copper using a battery of microbiotests.

Science.gov (United States)

Kungolos, A; Emmanouil, C; Tsiridis, V; Tsiropoulos, N

2009-08-01

Three commonly used test organisms of different trophic levels (Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna) were exposed to selected agrochemicals (fosthiazate, metalaxyl-M, imidacloprid) and copper, in single doses or in binary mixtures. The toxicity of each single compound varied up to two orders of magnitude, depending on the test species examined. V. fischeri was the most sensitive test organism regarding fosthiazate and metalaxyl-M, indicating an IC(50) value of 0.20 mg/L (0.17-0.25 mg/L) and 0.88 mg/L (0.35-1.57 mg/L), respectively. Imidacloprid was the least toxic compound, indicating an EC(50) value on D. magna of 64.6 mg/L (43.3-122.5 mg/L) and an IC(50) value on V. fischeri of 226 mg/L (159-322 mg/L), while for imidacloprid at a concentration of 1000 mg/L the effect on P. subcapitata was lower than 50%. Copper was the most toxic compound towards all test organisms exhibiting the highest toxic effect on P. subcapitata, with an IC(50) value of 0.05 mg/L (0.003-0.008 mg/L). The toxic effects of the binary mixtures have been compared to the theoretically expected effect, resulting from a simple mathematical model based on the theory of probabilities. The independent action model was used in order to predict the theoretically expected effect. The interactive effects were mostly antagonistic or additive, while in few cases (interactive effects of metalaxyl-M and copper on V. fischeri) a synergistic mode of action was observed for some concentration combinations. Experiments showed that interactive effects of chemicals may vary depending on the test species used as well as on the chemicals and their respective concentrations. Although most of the concentrations of chemicals tested in this study are higher than the ones usually found in natural environment, the evaluation of their interactive toxic effects using a battery of bioassays may comprise a useful tool for the estimation of the environmental hazard of chemicals.

Crystal Structure of a Plant Multidrug and Toxic Compound Extrusion Family Protein.

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Tanaka, Yoshiki; Iwaki, Shigehiro; Tsukazaki, Tomoya

2017-09-05

The multidrug and toxic compound extrusion (MATE) family of proteins consists of transporters responsible for multidrug resistance in prokaryotes. In plants, a number of MATE proteins were identified by recent genomic and functional studies, which imply that the proteins have substrate-specific transport functions instead of multidrug extrusion. The three-dimensional structure of eukaryotic MATE proteins, including those of plants, has not been reported, preventing a better understanding of the molecular mechanism of these proteins. Here, we describe the crystal structure of a MATE protein from the plant Camelina sativa at 2.9 Å resolution. Two sets of six transmembrane α helices, assembled pseudo-symmetrically, possess a negatively charged internal pocket with an outward-facing shape. The crystal structure provides insight into the diversity of plant MATE proteins and their substrate recognition and transport through the membrane. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of bismuth in environmental samples by ICP-MS and basic examination of cell toxicity for their compounds

International Nuclear Information System (INIS)

Kobayashi, Jun; Matsukawa, Takehisa; Chiba, Momoko; Yokoyama, Kazuhito; Terada, Hiroshi; Sugiyama, Hideo

2011-01-01

We examined both bismuth content levels in some environmental water samples (tapwater, bottled drinking water and slag obtained by sewage disposal) by inductively coupled plasma mass spectrometry (ICP-MS) and cultured cell toxicity of their compounds by the MTT assay. For ICP-MS, the conditions examined were addition of internal standard (IS), apparatus condition, and determination range, etc. When we examined an IS, the advantage was not clear that the ICP-MS response of the IS candidate elements was very variable. However, the sample induction rate into ICP-MS is more changeable at any time. Since the correction of analytical results was enabled by the addition of IS, Tl-203 was selected for IS, and was used in this study. The determination lower limit was 11 ppt by using 10 ppb Tl. Bi was detected in a few environmental water samples at 20.4 ppt - 6.8 ppb (0.07-6.83 μg/g original slags), but Bi concentrations of most samples were lower than the determination limit. On the other hand, concerning cell toxicity, the subgallate and free gallic acid affected the lives of cultured cells. Especially, the toxicity of free gallic acid was higher. It has been understood that the toxicity is weakly adjusted by chelating with Bi. (author)

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

OpenAIRE

Worapot Suntornsuk; Donlaporn Saetae

2010-01-01

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 ob...

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

Science.gov (United States)

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

2014-01-01

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.

Effective anti-leishmanial activity of minimalist squaramide-based compounds.

Science.gov (United States)

Marín, Clotilde; Ximenis, Marta; Ramirez-Macías, Inmaculada; Rotger, Carmen; Urbanova, Kristina; Olmo, Francisco; Martín-Escolano, Rubén; Rosales, María José; Cañas, Rocio; Gutierrez-Sánchez, Ramón; Costa, Antonio; Sánchez-Moreno, Manuel

2016-11-01

In order to evaluate the in vitro leishmanicidal activity of N,N'-Squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against Leishmania infantum, Leishmania braziliensis and Leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. Infectivity and cytotoxicity tests were performed on J774.2 macrophage cells using meglumine antimoniate (Glucantime) as the reference drug. Changes in metabolite excretion by 1 H-NMR and the ultrastructural alterations occurring in the parasites treated using transmission electron microscopy (TEM), was analyzed. Compounds 1, 7, 11, 14 and 17 were the more active and less toxic. Infection rates showed that the order of effectiveness was 17 > 11 > 14 > 7 for both L. infantum and L. braziliensis and in the same way, the compound 1 for L. donovani. All these compounds have altered the typical structure of the promastigotes, glycosomes and mitochondria. These severe modifications by the compounds are the ultimate reasons for the alterations observed in the excretion products. The Squaramide 17 (3-(butylamino)-4-((3-(dimetilamino)propyl)(methyl)amino)cyclobut-3-en-1,2-dione) was clearly the most efficient of all compounds. The data appear to confirm that the severe modifications generated in organelles such as glycosomes or mitochondria by the compounds are the ultimate reasons for the alterations observed in the excretion products of all species. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-leishmanial agent. Copyright © 2016. Published by Elsevier Inc.

Toxicity research of boron-nitrogen modifiers of wooden surface

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Klyachenkova Ol'ga Aleksandrovna

2014-07-01

Full Text Available Boron-nitrogen compounds (BNC have been successfully used to create bio- and fire-protective compositions for wood. Within the framework of this study, our aim was to assess the toxicity of the boron-nitrogen compounds by bioluminescent method with the use of environmental control device "Biotox-10M" and highly sensitive biosensor "Ecolum". We also defined toxicological parameters EC20 and EC50 and concluded, that all the wood preservation compounds are highly toxic, whereby, it is advisable to use them for external protection of wooden structures. As a result of BNC toxicity assessment, it is necessary to consider that any effective bio- and fireprotectives, will be highly toxic. Our researches stated, that BNC protective compositions are highly toxic and, therefore, it is possible to conclude their applicability for external wood processing.

Volatile organic compounds emitted by filamentous fungi isolated from flooded homes after Hurricane Sandy show toxicity in a Drosophila bioassay.

Science.gov (United States)

Zhao, G; Yin, G; Inamdar, A A; Luo, J; Zhang, N; Yang, I; Buckley, B; Bennett, J W

2017-05-01

Superstorm Sandy provided an opportunity to study filamentous fungi (molds) associated with winter storm damage. We collected 36 morphologically distinct fungal isolates from flooded buildings. By combining traditional morphological and cultural characters with an analysis of ITS sequences (the fungal DNA barcode), we identified 24 fungal species that belong to eight genera: Penicillium (11 species), Fusarium (four species), Aspergillus (three species), Trichoderma (two species), and one species each of Metarhizium, Mucor, Pestalotiopsis, and Umbelopsis. Then, we used a Drosophila larval assay to assess possible toxicity of volatile organic compounds (VOCs) emitted by these molds. When cultured in a shared atmosphere with growing cultures of molds isolated after Hurricane Sandy, larval toxicity ranged from 15 to 80%. VOCs from Aspergillus niger 129B were the most toxic yielding 80% mortality to Drosophila after 12 days. The VOCs from Trichoderma longibrachiatum 117, Mucor racemosus 138a, and Metarhizium anisopliae 124 were relatively non-toxigenic. A preliminary analysis of VOCs was conducted using solid-phase microextraction-gas chromatography-mass spectrometry from two of the most toxic, two of the least toxic, and two species of intermediate toxicity. The more toxic molds produced higher concentrations of 1-octen-3-ol, 3-octanone, 3-octanol, 2-octen-1-ol, and 2-nonanone; while the less toxic molds produced more 3-methyl-1-butanol and 2-methyl-1-propanol, or an overall lower amount of volatiles. Our data support the hypothesis that at certain concentrations, some VOCs emitted by indoor molds are toxigenic. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Science.gov (United States)

Geiss, K T; Frazier, J M

2001-07-02

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

INVESTIGATING THE ENANTIOSELECTIVE TOXICITY OF CONAZOLE FUNGICIDES IN RAINBOW TROUT THROUGH NMR BASED METABOLOMICS

Science.gov (United States)

Recently, metabolomics, or the quantitative measurement of a broad spectrum of metabolic responses of living systems in response to disease onset or genetic modification, has been employed to enable rapid identification of the mechanisms of toxicity for compounds of environmental...

Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

Energy Technology Data Exchange (ETDEWEB)

Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands); Pronk, Tessa E. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht (Netherlands); Brandhof, Evert-Jan van den [Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Ven, Leo T.M. van der [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)

2013-10-01

The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.

The toxicity of sulfolane and DIPA from sour gas plants to aquatic species

International Nuclear Information System (INIS)

Lintott, D.R.; Goudey, J.S.; Wilson, J.; Swanson, S.; Drury, C.

1997-01-01

The ecological effects of sulfolane and diisopropanolamine (DIPA), which are used to remove sulfur compounds from natural gas, were studied to establish risk-based cleanup criteria and to evaluate effective remedial measures. Toxicity tests were conducted on both the parent compounds and the thermal and biological degradation products. Toxicity testing focused on aquatic species because surface outlets, such as creeks, were found to be the major pathways for the water soluble DIPA and sulfolane chemicals. Sulfolane proved to be relatively non-toxic to aquatic species, with the exception of bacteria. DIPA was relatively toxic to algae at pH found in ground and surface waters. Aqueous and methanol reclaimer bottom extracts from five different gas plant sites were also tested using modified acute toxicity screening tests with different species. The reclaimer bottoms were found to be highly toxic to all species tested. DIPA and sulfolane did not entirely account for the toxicity of the reclaimer bottoms. Inorganic salts and metals present in reclaimer bottoms were found not to contribute to toxicity directly. The same was true for DIPA and sulfolane degradation products. 3 refs., 7 tabs., 8 figs

The toxicity of sulfolane and DIPA from sour gas plants to aquatic species

Energy Technology Data Exchange (ETDEWEB)

Lintott, D.R.; Goudey, J.S. [HydroQual Consultants, Inc., Calgary, AB (Canada); Wilson, J.; Swanson, S. [Golder Associates, Calgary, AB (Canada); Drury, C. [Shell Canada Ltd., Calgary, AB (Canada). Calgary Research Centre

1997-12-31

The ecological effects of sulfolane and diisopropanolamine (DIPA), which are used to remove sulfur compounds from natural gas, were studied to establish risk-based cleanup criteria and to evaluate effective remedial measures. Toxicity tests were conducted on both the parent compounds and the thermal and biological degradation products. Toxicity testing focused on aquatic species because surface outlets, such as creeks, were found to be the major pathways for the water soluble DIPA and sulfolane chemicals. Sulfolane proved to be relatively non-toxic to aquatic species, with the exception of bacteria. DIPA was relatively toxic to algae at pH found in ground and surface waters. Aqueous and methanol reclaimer bottom extracts from five different gas plant sites were also tested using modified acute toxicity screening tests with different species. The reclaimer bottoms were found to be highly toxic to all species tested. DIPA and sulfolane did not entirely account for the toxicity of the reclaimer bottoms. Inorganic salts and metals present in reclaimer bottoms were found not to contribute to toxicity directly. The same was true for DIPA and sulfolane degradation products. 3 refs., 7 tabs., 8 figs.

Development of multicomponent parts-per-billion-level gas standards of volatile toxic organic compounds

International Nuclear Information System (INIS)

Rhoderick, G.C.; Zielinski, W.L. Jr.

1990-01-01

This paper reports that the demand for stable, low-concentration multicomponent standards of volatile toxic organic compounds for quantifying national and state measurement of ambient air quality and hazardous waste incineration emissions has markedly increased in recent years. In response to this demand, a microgravimetric technique was developed and validated for preparing such standards; these standards ranged in concentration from several parts per million (ppm) down to one part per billion (ppb) and in complexity from one organic up to 17. Studies using the gravimetric procedure to prepare mixtures of different groups of organics. including multi-components mixtures in the 5 to 20 ppb range, revealed a very low imprecision. This procedure is based on the separate gravimetric introduction of individual organics into an evacuated gas cylinder, followed by the pressurized addition of a precalculated amount of pure nitrogen. Additional studies confirmed the long-term stability of these mixtures. The uncertainty of the concentrations of the individual organics at the 95% confidence level ranged from less than 1% relative at 1 ppm to less than 10% relative at 1 ppb. Over 100 primary gravimetric standards have been developed, validated, and used for certifying the concentrations of a variety of mixtures for monitoring studies

Insecticidal Activity of Cyanohydrin and Monoterpenoid Compounds

Directory of Open Access Journals (Sweden)

Joel R. Coats

2000-04-01

Full Text Available The insecticidal activities of several cyanohydrins, cyanohydrin esters and monoterpenoid esters (including three monoterpenoid esters of a cyanohydrin were evaluated. Topical toxicity to Musca domestica L. adults was examined, and testing of many compounds at 100 mg/fly resulted in 100% mortality. Topical LD50 values of four compounds for M. domestica were calculated. Testing of many of the reported compounds to brine shrimp (Artemia franciscana Kellog resulted in 100% mortality at 10 ppm, and two compounds caused 100% mortality at 1 ppm. Aquatic LC50 values were calculated for five compounds for larvae of the yellow fever mosquito (Aedes aegypti (L.. Monoterpenoid esters were among the most toxic compounds tested in topical and aquatic bioassays.

SYNTHESIZING DERIVATIVES FROM CYCLOPENTANONE ANALOGUE CURCUMIN AND THEIR TOXIC, ANTIOXIDANT AND ANTI-INFLAMMATORY ACTIVITIES

Directory of Open Access Journals (Sweden)

Adel Zamri1

2011-11-01

Full Text Available Three types of cyclopentanone derivatives have been synthesized from aromatic aldehyde and ketone derivatives undera base condition through aldol condensation. These cyclopentanone products were 2,5-dibenzylidene-cyclopentanone(a, 2,5-bis-(4-hydroxy-benzylidene-cyclopentanone (b, and 2,5-bis-(4-hydroxy-benzylidene-cyclopentanone (cwhich has a yield of 63-99%. The chemical structure of these compounds were determined using UV, IR and NMRspectroscopy. In order to clarify the role of hydroxyl and amine moieties, toxic, antioxidant and anti-inflammatoryactivities were carried out. The toxic test indicated that the compounds showed strong toxicity. In addition, the presenceof hydroxyl and amine groups on both rings of curcumin increased the antioxidant and anti-inflammatory activities

Stabilizing the baseline current of a microbial fuel cell-based biosensor through overpotential control under non-toxic conditions.

Science.gov (United States)

Stein, Nienke E; Hamelers, Hubertus V M; Buisman, Cees N J

2010-04-01

A MFC-based biosensor can act as online toxicity sensor. Electrical current is a direct linear measure for metabolic activity of electrochemically active microorganisms. Microorganisms gain energy from anodic overpotential and current strongly depends on anodic overpotential. Therefore control of anodic overpotential is necessary to detect toxic events and prevent false positive alarms. Anodic overpotential and thus current is influenced by anode potential, pH, substrate and bicarbonate concentrations. In terms of overpotential all factor showed a comparable effect, anode potential 1.2% change in current density per mV, pH 0.43%/mV, bicarbonate 0.75%/mV and acetate 0.8%/mV. At acetate saturation the maximum acetate conversion rate is reached and with that a constant bicarbonate concentration. Control of acetate and bicarbonate concentration can be less strict than control of anode potential and pH. Current density changes due to changing anode potential and pH are in the same order of magnitude as changes due to toxicity. Strict control of pH and anode potential in a small range is required. The importance of anodic overpotential control for detection of toxic compounds is shown. To reach a stable baseline current under nontoxic conditions a MFC-based biosensor should be operated at controlled anode potential, controlled pH and saturated substrate concentrations. 2009 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Estimate of the prevalence and burden of food poisoning by natural toxic compounds in South Korea.

Science.gov (United States)

Park, Myoung Su; Bahk, Gyung Jin

2015-12-01

Many studies have attempted to accurately estimate the overall number of cases of foodborne illness, but there have not been many attempts to estimate the burden of foodborne disease caused by natural toxic compounds. This study estimated the number of cases due to specific natural toxins (seafood toxins, plant toxins, and mycotoxins) during 2008-2012 in South Korea, using data from the Health Insurance Review and Assessment Service (HIRA), while accounting for uncertainty in the estimate. The estimated annual occurrences of foodborne illness from natural toxic agents were 1088 (90% credible interval [CrI]: 883-1315), which suggests there are 21 times more cases than are reported, with 45.6% (n=496 [388-614]) and 54.4% (n=592 [423-790]), accounting for inpatient stays and outpatient visits, respectively. Among toxins, mushroom and plant toxins caused the highest illnesses, followed by toxic agents in seafood and mycotoxins. The 55-59year olds had the highest proportion of illnesses and those over the age of 40 accounted for 70.6% of all cases. The cases caused by mushroom poison, poisonous plants, and seafood toxins showed clear seasonal and regional differences. These results will be useful to food safety policymakers for the prevention and control of natural food poisons in South Korea. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae).

Science.gov (United States)

Ortega-Insaurralde, I; Toloza, A C; Gonzalez-Audino, P; Mougabure-Cueto, G A; Alvarez-Costa, A; Roca-Acevedo, G; Picollo, M I

2015-09-01

In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sediment contamination of residential streams in the metropolitan kansas city area, USA: Part II. whole-sediment toxicity to the amphipod hyalella azteca

Science.gov (United States)

Tao, J.; Ingersoll, C.G.; Kemble, N.E.; Dias, J.R.; Murowchick, J.B.; Welker, G.; Huggins, D.

2010-01-01

This is the second part of a study that evaluates the influence of nonpoint sources on the sediment quality of five adjacent streams within the metropolitan Kansas City area, central United States. Physical, chemical, and toxicity data (Hyalella azteca 28-day whole-sediment toxicity test) for 29 samples collected in 2003 were used for this evaluation, and the potential causes for the toxic effects were explored. The sediments exhibited a low to moderate toxicity, with five samples identified as toxic to H. azteca. Metals did not likely cause the toxicity based on low concentrations of metals in the pore water and elevated concentrations of acid volatile sulfide in the sediments. Although individual polycyclic aromatic hydrocarbons (PAHs) frequently exceeded effect-based sediment quality guidelines [probable effect concentrations (PECs)], only four of the samples had a PEC quotient (PEC-Q) for total PAHs over 1.0 and only one of these four samples was identified as toxic. For the mean PEC-Q for organochlorine compounds (chlordane, dieldrin, sum DDEs), 4 of the 12 samples with a mean PEC-Q above 1.0 were toxic and 4 of the 8 samples with a mean PEC-Q above 3.0 were toxic. Additionally, four of eight samples were toxic, with a mean PEC-Q above 1.0 based on metals, PAHs, polychlorinated biphenyls (PCBs), and organochlorine pesticides. The increase in the incidence of toxicity with the increase in the mean PEC-Q based on organochlorine pesticides or based on metals, PAHs, PCBs, and organochlorine pesticides suggests that organochlorine pesticides might have contributed to the observed toxicity and that the use of a mean PEC-Q, rather than PEC-Qs for individual compounds, might be more informative in predicting toxic effects. Our study shows that stream sediments subject to predominant nonpoint sources contamination can be toxic and that many factors, including analysis of a full suite of PAHs and pesticides of both past and present urban applications and the origins of

Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants.

Science.gov (United States)

Ntie-Kang, Fidele; Simoben, Conrad Veranso; Karaman, Berin; Ngwa, Valery Fuh; Judson, Philip Neville; Sippl, Wolfgang; Mbaze, Luc Meva'a

2016-01-01

Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Güner-Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa's expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space.

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: shitanda@rs.noda.tus.ac.jp; 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)

2009-08-30

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.

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

International Nuclear Information System (INIS)

Shitanda, Isao; Takamatsu, Satoshi; Watanabe, Kunihiro; Itagaki, Masayuki

2009-01-01

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 ' 50 ) for atrazine and DCMU were 12 and 1 μmol dm -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.

APPLICATION OF JET REMPI AND LIBS TO AIR TOXIC MONITORING

Science.gov (United States)

The paper discusses three advanced, laser-based monitoring techniques that the EPA is assisting in developing for real time measurement of toxic aerosol compounds. One of the three techniques is jet resonance enhanced multiphoton ionization (Jet REMPI) coupled with a time-of-flig...

Bolevenine, a toxic protein from the Japanese toadstool Boletus venenatus.

Science.gov (United States)

Matsuura, Masanori; Yamada, Mina; Saikawa, Yoko; Miyairi, Kazuo; Okuno, Toshikatsu; Konno, Katsuhiro; Uenishi, Jun'ichi; Hashimoto, Kimiko; Nakata, Masaya

2007-03-01

A toxic protein, called bolevenine, was isolated from the toxic mushroom Boletus venenatus based on its lethal effects on mice. On SDS-PAGE, in either the presence or absence of 2-mercaptoethanol, this protein showed a single band of approximately 12 kDa. In contrast, based on gel filtration and MALDI-TOFMS, its relative molecular mass was estimated to be approximately 30 kDa and approximately 33 kDa, respectively, indicating that the protein consists of three identical subunits. This toxin exhibited its lethal activity following injection at 10mg/kg into mice. The N-terminal amino acid sequence was determined up to 18, and found to be similar to the previously reported bolesatine, a toxic compound isolated from Boletus satanas.

Acute toxicity of ingested fluoride.

Science.gov (United States)

Whitford, Gary Milton

2011-01-01

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

The volatile compound BinBase mass spectral database.

Science.gov (United States)

Skogerson, Kirsten; Wohlgemuth, Gert; Barupal, Dinesh K; Fiehn, Oliver

2011-08-04

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. 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://vocbinbase.fiehnlab.ucdavis.edu). The BinBase

The volatile compound BinBase mass spectral database

Directory of Open Access Journals (Sweden)

Barupal Dinesh K

2011-08-01

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

Environmental levels, toxicity and human exposure to tributyltin (TBT)-contaminated marine environment. a review. b_antizar@hotmail.com.

Science.gov (United States)

Antizar-Ladislao, Blanca

2008-02-01

Tributyltin (TBT) is a toxic chemical used for various industrial purposes such as slime control in paper mills, disinfection of circulating industrial cooling waters, antifouling agents, and the preservation of wood. Due to its widespread use as an antifouling agent in boat paints, TBT is a common contaminant of marine and freshwater ecosystems exceeding acute and chronic toxicity levels. TBT is the most significant pesticide in marine and freshwaters in Europe and consequently its environmental level, fate, toxicity and human exposure are of current concern. Thus, the European Union has decided to specifically include TBT compounds in its list of priority compounds in water in order to control its fate in natural systems, due to their toxic, persistent, bioaccumulative and endocrine disruptive characteristics. Additionally, the International Maritime Organization has called for a global treaty that bans the application of TBT-based paints starting 1 of January 2003, and total prohibition by 1 of January 2008. This paper reviews the state of the science regarding TBT, with special attention paid to the environmental levels, toxicity, and human exposure. TBT compounds have been detected in a number of environmental samples. In humans, organotin compounds have been detected in blood and in the liver. As for other persistent organic pollutants, dietary intake is most probably the main route of exposure to TBT compounds for the general population. However, data concerning TBT levels in foodstuffs are scarce. It is concluded that investigations on experimental toxicity, dietary intake, potential human health effects and development of new sustainable technologies to remove TBT compounds are clearly necessary.

The effects of characteristics of substituents on toxicity of the nitroaromatics: HiT QSAR study

Science.gov (United States)

Kuz'min, Victor E.; Muratov, Eugene N.; Artemenko, Anatoly G.; Gorb, Leonid; Qasim, Mohammad; Leszczynski, Jerzy

2008-10-01

The present study applies the Hierarchical Technology for Quantitative Structure-Activity Relationships (HiT QSAR) for (i) evaluation of the influence of the characteristics of 28 nitroaromatic compounds (some of which belong to a widely known class of explosives) as to their toxicity; (ii) prediction of toxicity for new nitroaromatic derivatives; (iii) analysis of the effects of substituents in nitroaromatic compounds on their toxicity in vivo. The 50% lethal dose concentration for rats (LD50) was used to develop the QSAR models based on simplex representation of molecular structure. The preliminary 1D QSAR results show that even the information on the composition of molecules reveals the main tendencies of changes in toxicity. The statistic characteristics for partial least squares 2D QSAR models are quite satisfactory ( R 2 = 0.96-0.98; Q 2 = 0.91-0.93; R 2 test = 0.89-0.92), which allows us to carry out the prediction of activity for 41 novel compounds designed by the application of new combinations of substituents represented in the training set. The comprehensive analysis of toxicity changes as a function of substituent position and nature was carried out. Molecular fragments that promote and interfere with toxicity were defined on the basis of the obtained models. It was shown that the mutual influence of substituents in the benzene ring plays a crucial role regarding toxicity. The influence of different substituents on toxicity can be mediated via different C-H fragments of the aromatic ring.

Fluoroacetate-mediated toxicity of fluorinated ethanes.

Science.gov (United States)

Keller, D A; Roe, D C; Lieder, P H

1996-04-01

A series of 1-(di)halo-2-fluoroethanes reported in the literature to be nontoxic or of low toxicity were found to be highly toxic by the inhalation route. Experiments were performed that showed the compounds, 1,2-difluoroethane, 1-chloro-2-fluoroethane, 1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane to be highly toxic to rats upon inhalation for 4 hr. All four compounds had 4-hr approximate lethal concentrations of difluoroethane (commonly referred to as HFC-152a) has very low acute toxicity with a 4-hr LC50 of > 400,000 ppm in rats. Rats exposed to the selected toxic fluoroethanes showed clinical signs of fluoroacetate toxicity (lethargy, hunched posture, convulsions). 1,2-Difluoroethane, 1-chloro-2-fluoroethane, 1-chloro-1,2-difluoroethane, and 1-bromo-2-fluoroethane were shown to increase concentrations of citrate in serum and heart tissue, a hallmark of fluoroacetate intoxication. 19F NMR analysis confirmed that fluoroacetate was present in the urine of rats exposed to each toxic compound. Fluorocitrate, a condensation product of fluoroacetate and oxaloacetate, was identified in the kidney of rats exposed to 1,2-difluoroethane. There was a concentration-related elevation of serum and heart citrate in rats exposed to 0-1000 ppm 1,2-fluoroethane. Serum citrate was increased up to 5-fold and heart citrate was increased up to 11-fold over control citrate levels. Metabolism of 1,2-difluoroethane by cytochrome P450 (most likely CYP2E1) is suspected because pretreatment of rats or mice with SKF-525F, disulfiram, or dimethyl sulfoxide prevented or delayed the toxicity observed in rats not pretreated. Experimental evidence indicates that the metabolism of the toxic fluoroethanes is initiated at the carbon-hydrogen bond, with metabolism to fluoroacetate via an aldehyde or an acyl fluoride. The results of these studies show that 1-(di)halo-2-fluoroethanes are highly toxic to rats and should be considered a hazard to humans unless demonstrated otherwise.

Identification of Chemical Toxicity Using Ontology Information of Chemicals

Directory of Open Access Journals (Sweden)

Zhanpeng Jiang

2015-01-01

Full Text Available With the advance of the combinatorial chemistry, a large number of synthetic compounds have surged. However, we have limited knowledge about them. On the other hand, the speed of designing new drugs is very slow. One of the key causes is the unacceptable toxicities of chemicals. If one can correctly identify the toxicity of chemicals, the unsuitable chemicals can be discarded in early stage, thereby accelerating the study of new drugs and reducing the R&D costs. In this study, a new prediction method was built for identification of chemical toxicities, which was based on ontology information of chemicals. By comparing to a previous method, our method is quite effective. We hope that the proposed method may give new insights to study chemical toxicity and other attributes of chemicals.

Acute Toxicity of a Recently Identified Phenol-based Synthetic ...

African Journals Online (AJOL)

This paper reports on the acute toxicity of a new phenol based synthetic tsetse fly repellent recently identified at the International Centre for Insect Physiology and Ecology (patent No. ... The repellent can be classified as being highly toxic with central nervous system (CNS) involvement and a mild skin and eye irritant.

Small molecule fluoride toxicity agonists.

Science.gov (United States)

Nelson, James W; Plummer, Mark S; Blount, Kenneth F; Ames, Tyler D; Breaker, Ronald R

2015-04-23

Fluoride is a ubiquitous anion that inhibits a wide variety of metabolic processes. Here, we report the identification of a series of compounds that enhance fluoride toxicity in Escherichia coli and Streptococcus mutans. These molecules were isolated by using a high-throughput screen (HTS) for compounds that increase intracellular fluoride levels as determined via a fluoride riboswitch reporter fusion construct. A series of derivatives were synthesized to examine structure-activity relationships, leading to the identification of compounds with improved activity. Thus, we demonstrate that small molecule fluoride toxicity agonists can be identified by HTS from existing chemical libraries by exploiting a natural fluoride riboswitch. In addition, our findings suggest that some molecules might be further optimized to function as binary antibacterial agents when combined with fluoride. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of Acute Toxicity of Algal Metabolites Using Bioluminescence Inhibition Assay

Directory of Open Access Journals (Sweden)

Hansa Jeswani

2015-01-01

Full Text Available Microalgae are reported to degrade hazardous compounds. However, algae, especially cyanobacteria are known to produce secondary metabolites which may be toxic to flora, fauna and human beings. The aim of this study was selection of an appropriate algal culture for biological treatment of biomass gasification wastewater based on acute toxicity considerations. The three algae that were selected were Spirulina sp., Scenedesmus abundans and a fresh water algal consortium. Acute toxicity of the metabolites produced by these algal cultures was tested at the end of log phase using the standard bioluminescence inhibition assay based on Vibrio fischeri NRRLB 11174. Scenedesmus abundans and a fresh water algal consortium dominated by cyanobacteria such as Phormidium, Chroococcus and Oscillatoria did not release much toxic metabolites at the end of log phase and caused only about 20% inhibition in bioluminescence. In comparison, Spirulina sp. released toxic metabolites and caused 50% bioluminescence inhibition at 3/5 times dilution of the culture supernatant (EC50.

[Glyphosate--a non-toxic pesticide?].

Science.gov (United States)

Pieniazek, Danuta; Bukowska, Bozena; Duda, Wirgiliusz

2003-01-01

Glyphosate is currently the most commonly applied herbicide and its use is still growing. Nowadays, over 50 commercial preparations containing this compound are used, and these formulations are much more toxic than their active compound, glyphosate, owing to the presence of many surfactants and carrier compounds. Toxicological investigations provide evidence that glyphosate is an extremely "safe" herbicide for animals. This is why its use in agriculture is universal. In June 1991, the Environmental Protection Agency (EPA) categorized this compound into class E (according to EPA there are five categories of carcinogenicity), which means that it is probably not carcinogenic to humans. Unfortunately, the study carried out by Swedish oncologists in 2001 showed that glyphosate may induce cancer of the lymphatic system. The results of the Swedish study have changed our opinion about "safety" of this herbicide. Investigations concerning both its accumulation and toxic effect in animals and plants are now under way in many laboratories.

An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells

International Nuclear Information System (INIS)

Noor, Fozia; Niklas, Jens; Mueller-Vieira, Ursula; Heinzle, Elmar

2009-01-01

Efficient and accurate safety assessment of compounds is extremely important in the preclinical development of drugs especially when hepatotoxicty is in question. Multiparameter and time resolved assays are expected to greatly improve the prediction of toxicity by assessing complex mechanisms of toxicity. An integrated approach is presented in which Hep G2 cells and primary rat hepatocytes are compared in frequently used cytotoxicity assays for parent compound toxicity. The interassay variability was determined. The cytotoxicity assays were also compared with a reliable alternative time resolved respirometric assay. The set of training compounds consisted of well known hepatotoxins; amiodarone, carbamazepine, clozapine, diclofenac, tacrine, troglitazone and verapamil. The sensitivity of both cell systems in each tested assay was determined. Results show that careful selection of assay parameters and inclusion of a kinetic time resolved assay improves prediction for non-metabolism mediated toxicity using Hep G2 cells as indicated by a sensitivity ratio of 1. The drugs with EC 50 values 100 μM or lower were considered toxic. The difference in the sensitivity of the two cell systems to carbamazepine which causes toxicity via reactive metabolites emphasizes the importance of human cell based in-vitro assays. Using the described system, primary rat hepatocytes do not offer advantage over the Hep G2 cells in parent compound toxicity evaluation. Moreover, respiration method is non invasive, highly sensitive and allows following the time course of toxicity. Respiration assay could serve as early indicator of changes that subsequently lead to toxicity.

FLUORIDE TOXICITY – A HARSH REALITY

OpenAIRE

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

2011-01-01

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

Toxicity identification evaluations of produced-water effluents

International Nuclear Information System (INIS)

Sauer, T.C.; Costa, H.J.; Brown, J.S.; Ward, T.J.

1997-01-01

Toxicity identification evaluations (TIEs) were performed on 14 produced-water (PW) samples of various salinities from inland and offshore oil- and gas-production facilities operated by different companies in Wyoming, Texas, California, and Louisiana (USA) to evaluate the efficacy of TIE procedures in determining potential toxicants in PW effluents. The research involved acute (24- and 48-h) freshwater and marine toxicity tests on whole PW and PW fractions generated by standard US Environmental Protection Agency and PW-specific fractionation schemes. Factors influencing PW TIEs were investigated, such as the effect of salinity in selecting fractionation manipulations, the effect of toxicity test replication (i.e., reproducibility) in distinguishing changes in toxicities between whole PW and its fractions, and the suitability of different test species in PW TIEs. The results obtained and lessons learned from conducting these PW TIEs are presented in this article. Components, or fractions, contributing to toxicity differed for each PW with no specific fraction being consistently toxic. For most PW samples, toxicity attributed to any one fraction represented only part of the toxicity of the whole sample. However, no more than two fraction types were identified as potential toxicants in any sample. Potential toxicants identified during this study, besides salinity, included acidic and basic organic compound class fractions, particulates removed by filtration at pH 11, ammonia, hydrocarbons, hydrogen sulfide, material removed by pH change, and volatile compounds

In Vitro Toxicity testing in the 21st Century

Directory of Open Access Journals (Sweden)

Erwin L Roggen

2011-02-01

Full Text Available The National Research Council (NRC article Toxicity Testing in the 21st Century: A vision and A Strategy (National Research Council, 2007 was written to bring attention to the application of scientific advances for use in toxicity tests so that chemicals can be tested in a more time and cost efficient manner while providing a more relevant and mechanistic insight into the toxic potential of a compound.Development of tools for in vitro toxicity testing constitutes an important activity of this vision and contributes to the provision of test systems as well as data that are essential for the development of computer modelling tools for e.g. system biology, physiologically-based modelling. This article intends to highlight some of the issues that have to be addressed in order to make in vitro toxicity testing a reality in the 21st century.

Toxicity of nonylphenol diethoxylate in lab-scale anaerobic digesters

DEFF Research Database (Denmark)

Bozkurt, Hande; Sanin, F. Dilek

2014-01-01

Nonylphenol compounds have high commercial, industrial and domestic uses owing to their surface active properties. In addition to their toxic, carcinogenic and persistent characteristics; they have drawn the attention of scientists lately due to their endocrine disrupting properties....... Their widespread use and disposal cause them to enter wastewater treatment systems at high concentrations. Since they are highly persistent and hydrophobic, they accumulate mostly on sludge.In this study using Anaerobic Toxicity Assay (ATA) tests, the toxicity of a model nonylphenol compound, nonylphenol...

Organometallic compounds in the environment

National Research Council Canada - National Science Library

Craig, P. J

2003-01-01

... of Organometallic Species in the Environment 20 1.10 Stability of Organometallic Compounds in Biological Systems 1.11 G eneral Comments on the Toxicities of Organometallic Compounds 22 1.12 General Considerations on Environmental R eactivity of Organometallic Compounds 24 1.13 Microbial Biotransformation of Metals and M etalloids 25 1.13.1 Introduction 25 1...

Is the OECD acute worm toxicity test environmentally relevant? The effect of mineral form on calculated lead toxicity

International Nuclear Information System (INIS)

Davies, N.A.Nicola A.; Hodson, M.E.Mark E.; Black, S.Stuart

2003-01-01

The current OECD acute worm toxicity test does not relate well to ambient conditions. - In a series of experiments the toxicity of lead to worms in soil was determined following the draft OECD earthworm reproduction toxicity protocol except that lead was added as solid lead nitrate, carbonate and sulphide rather than as lead nitrate solution as would normally be the case. The compounds were added to the test soil to give lead concentrations of 625-12500 μg Pb g -1 of soil. Calculated toxicities of the lead decreased in the order nitrate>carbonate>sulphide, the same order as the decrease in the solubility of the metal compounds used. The 7-day LC 50 (lethal concentration when 50% of the population is killed) for the nitrate was 5321±275 μg Pb g -1 of soil and this did not change with time. The LC 50 values for carbonate and sulphide could not be determined at the concentration ranges used. The only parameter sensitive enough to distinguish the toxicities of the three compounds was cocoon (egg) production. The EC 50 s for cocoon production (the concentration to produce a 50% reduction in cocoon production) were 993, 8604 and 10246 μg Pb g -1 of soil for lead nitrate, carbonate and sulphide, respectively. Standard toxicity tests need to take into account the form in which the contaminant is present in the soil to be of environmental relevance

Toxicity of Kalanchoe spp to chicks.

Science.gov (United States)

Williams, M C; Smith, M C

1984-03-01

Leaves of Kalanchoe daigremontiana, K tubiflora, K fedtschenkoi, K tomentosa, K tomentosa X K beharensis, and 4 cultivars of K blossfeldiana were tested for toxicity to 2-week-old Leghorn chicks. These species were analyzed for percentage of alkaloids, aliphatic nitro compounds, soluble oxalates, and nitrates and were examined qualitatively for cyanogenic glycosides. The solubility of the toxic principle in K daigremontiana was determined. Leaves of K daigremontiana, K tubiflora, and K fedtschenkoi were toxic to chicks at dosage levels of 8 to 12 mg/g of body weight. Toxic signs included depression, muscular incoordination, twitching and spiraling of the neck, tremors, convulsions, paralysis, and death. Kalanchoe tomentosa, K tomentosa X K beharensis, and 4 cultivars of K blossfeldiana were nontoxic at the highest dosage levels tested. Aliphatic nitro compounds and cyanogenic glycosides were not detected in any species. Alkaloids, nitrates, and soluble oxalates were present only in nontoxic concentrations. The toxic principle in K daigremontiana was soluble in 50%, 80%, and 100% ethanol, slightly soluble in water and acetone, and insoluble in benzene, chloroform, and ether.

Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

Energy Technology Data Exchange (ETDEWEB)

Nowell, Lisa H., E-mail: lhnowell@usgs.gov [U.S. Geological Survey, California Water Science Center, Placer Hall, 6000 J Street, Sacramento, CA 95819 (United States); Norman, Julia E., E-mail: jnorman@usgs.gov [U.S. Geological Survey, Oregon Water Science Center, 2130 SW 5" t" h Avenue, Portland, OR 97201 (United States); Ingersoll, Christopher G., E-mail: cingersoll@usgs.gov [U.S. Geological Survey, Columbia Environmental Research Center, 4200 New Haven Road, Columbia, MO 65021 (United States); Moran, Patrick W., E-mail: pwmoran@usgs.gov [U.S. Geological Survey, Washington Water Science Center, 934 Broadway, Suite 300, Tacoma, WA 98402 (United States)

2016-04-15

Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical/chemical characteristics

Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

International Nuclear Information System (INIS)

Nowell, Lisa H.; Norman, Julia E.; Ingersoll, Christopher G.; Moran, Patrick W.

2016-01-01

Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical/chemical characteristics

Water quality, selected chemical characteristics, and toxicity of base flow and urban stormwater in the Pearson Creek and Wilsons Creek Basins, Greene County, Missouri, August 1999 to August 2000

Science.gov (United States)

Richards, Joseph M.; Johnson, Byron Thomas

2002-01-01

The chemistry and toxicity of base flow and urban stormwater were characterized to determine if urban stormwater was degrading the water quality of the Pearson Creek and Wilsons Creek Basins in and near the city of Springfield, Greene County, Missouri. Potentially toxic components of stormwater (nutrients, trace metals, and organic compounds) were identified to help resource managers identify and minimize the sources of toxicants. Nutrient loading to the James River from these two basins (especially the Wilsons Creek Basin) is of some concern because of the potential to degrade downstream water quality. Toxicity related to dissolved trace metal constituents in stormwater does not appear to be a great concern in these two basins. Increased heterotrophic activity, the result of large densities of fecal indicator bacteria introduced into the streams after storm events, could lead to associated dissolved oxygen stress of native biota. Analysis of stormwater samples detected a greater number of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) than were present in base-flow samples. The number and concentrations of pesticides detected in both the base-flow and stormwater samples were similar.Genotoxicity tests were performed to determine the bioavilability of chemical contaminants and determine the potential harmful effects on aquatic biota of Pearson Creek and Wilsons Creek. Genotoxicity was determined from dialysates from both long-term (approximately 30 days) and storm-event (3 to 5 days) semipermeable membrane device (SPMD) samples that were collected in each basin. Toxicity tests of SPMD samples indicated evidence of genotoxins in all SPMD samples. Hepatic activity assessment of one long-term SPMD sample indicated evidence of contaminant uptake in fish. Chemical analyses of the SPMD samples found that relatively few pesticides and pesticide metabolites had been sequestered in the lipid material of the SPMD; however, numerous PAHs and

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

Science.gov (United States)

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

2015-01-01

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.

Toxicity of pyrolysis gases from polyether sulfone

Science.gov (United States)

Hilado, C. J.; Olcomendy, E. M.

1979-01-01

A sample of polyether sulfone was evaluated for toxicity of pyrolysis gases, using the toxicity screening test method developed at the University of San Francisco. Animal response times were relatively short at pyrolysis temperatures of 600 to 800 C, with death occurring within 6 min. The principal toxicant appeared to be a compound other than carbon monoxide.

Evaluation of acute toxicity of essential oil of garlic (Allium sativum) and its selected major constituent compounds against overwintering Cacopsylla chinensis (Hemiptera: Psyllidae).

Science.gov (United States)

Zhao, Na Na; Zhang, Hang; Zhang, Xue Chang; Luan, Xiao Bing; Zhou, Cheng; Liu, Qi Zhi; Shi, Wang Peng; Liu, Zhi Long

2013-06-01

In our screening program for insecticidal activity of the essential oils/extracts derived from some Chinese medicinal herbs and spices, garlic (Allium sativum L.) essential oil was found to possess strong insecticidal activity against overwintering adults of Cacopsylla chinensis Yang et Li (Hemiptera: Psyllidae). The commercial essential oil of A. sativum was analyzed by gas chromatography-mass spectrometry. Sixteen compounds, accounting for 97.44% of the total oil, were identified, and the main components of the essential oil of A. sativum were diallyl trisulfide (50.43%), diallyl disulfide (25.30%), diallyl sulfide (6.25%), diallyl tetrasulfide (4.03%), 1,2-dithiolane (3.12%), allyl methyl disulfide (3.07%), 1,3-dithiane (2.12%), and allyl methyl trisulfide (2.08%). The essential oil of A. sativum possessed contact toxicity against overwintering C. chinensis, with an LC50 value of 1.42 microg per adult. The two main constituent compounds, diallyl trisulfide and diallyl disulfide, exhibited strong acute toxicity against the overwintering C. chinensis, with LC50 values of 0.64 and 11.04 /g per adult, respectively.

Investigating the application of a nitroreductase-expressing transgenic zebrafish line for high-throughput toxicity testing

Directory of Open Access Journals (Sweden)

Anna C. Chlebowski

Full Text Available Nitroreductase enzymes are responsible for the reduction of nitro functional groups to amino functional groups, and are found in a range of animal models, zebrafish (Danio rerio excluded. Transgenic zebrafish models have been developed for tissue-specific cell ablation, which use nitroreductase to ablate specific tissues or cell types following exposure to the non-toxic pro-drug metronidazole (MTZ. When metabolized by nitroreductase, MTZ produces a potent cytotoxin, which specifically ablates the tissue in which metabolism occurs. Uses, beyond tissue-specific cell ablation, are possible for the hepatocyte-specific Tg(l-fabp:CFP-NTRs891 zebrafish line, including investigations of the role of nitroreductase in the toxicity of nitrated compounds. The hepatic ablation characteristics of this transgenic line were explored, in order to expand its potential uses. Embryos were exposed at 48, 72, or 96 h post fertilization (hpf to a range of MTZ concentrations, and the ablation profiles were compared. Ablation occurred at a 10-fold lower concentration than previously reported. Embryos were exposed to a selection of other compounds, with and without MTZ, in order to investigate alternative uses for this transgenic line. Test compounds were selected based on: their ability to undergo nitroreduction, known importance of hepatic metabolism to toxicity, and known pharmaceutical hepatotoxins. Selected compounds included nitrated polycyclic aromatic hydrocarbons (nitro-PAHs, the PAHs retene and benzo[a]pyrene, and the pharmaceuticals acetaminophen and flutamide. The results suggest a range of potential roles of the liver in the toxicity of these compounds, and highlight the additional uses of this transgenic model in toxicity testing. Keywords: Zebrafish, Transgenic, Nitroreductase, Nitrated polycyclic aromatic hydrocarbon, Tissue ablation, Pharmaceuticals

Thermochemical Wastewater Valorization via Enhanced Microbial Toxicity Tolerance

Energy Technology Data Exchange (ETDEWEB)

Beckham, Gregg T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Thelhawadigedara, Lahiru Niroshan Jayakody [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Johnson, Christopher W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Pleitner, Brenna P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Cleveland, Nicholas S [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Michener, William E [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Olstad-Thompson, Jessica L [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Vardon, Derek R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Whitham, Jason M. [Oak Ridge National Laboratory; Giannone, Richard J. [Oak Ridge National Laboratory; Klingeman, Dawn M. [Oak Ridge National Laboratory; Brown, Robert C. [Iowa State University; Brown, Steven D. [Oak Ridge National Laboratory; LanzaTech, Inc.; Hettich, Robert L. [Oak Ridge National Laboratory; Guss, Adam M. [Oak Ridge National Laboratory

2018-04-17

Thermochemical (TC) biomass conversion processes such as pyrolysis and liquefaction generate considerable amounts of wastewater, which often contains highly toxic compounds that are incredibly challenging to convert via standard wastewater treatment approaches such as anaerobic digestion. These streams represent a cost for TC biorefineries, and a potential valorization opportunity, if effective conversion methods are developed. The primary challenge hindering microbial conversion of TC wastewater is toxicity. In this study, we employ a robust bacterium, Pseudomonas putida, with TC wastewater streams to demonstrate that aldehydes are the most inhibitory compounds in these streams. Proteomics, transcriptomics, and fluorescence-based immunoassays of P. putida grown in a representative wastewater stream indicate that stress results from protein damage, which we hypothesize is a primary toxicity mechanism. Constitutive overexpression of the chaperone genes, groEL, groES, and clpB, in a genome-reduced P. putida strain improves the tolerance towards multiple TC wastewater samples up to 200-fold. Moreover, the concentration ranges of TC wastewater are industrially relevant for further bioprocess development for all wastewater streams examined here, representing different TC process configurations. Furthermore, we demonstrate proof-of-concept polyhydroxyalkanoate production from the usable carbon in an exemplary TC wastewater stream. Overall, this study demonstrates that protein quality control machinery and repair mechanisms can enable substantial gains in microbial tolerance to highly toxic substrates, including heterogeneous waste streams. When coupled to other metabolic engineering advances such as expanded substrate utilization and enhanced product accumulation, this study generally enables new strategies for biological conversion of highly-toxic, organic-rich wastewater via engineered aerobic monocultures or designer consortia.

Interpreting in vitro developmental toxicity test battery results: The consideration of toxicokinetics

NARCIS (Netherlands)

Bosgra, S.; Westerhout, J.

2015-01-01

In the EU collaborative project ChemScreen an alternative, in vitro assay-based test strategy was developed to screen compounds for reproductive toxicity. A toxicokinetic modeling approach was used to allow quantitative comparison between effective concentrations in the in vitro test battery and

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

Science.gov (United States)

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

2017-01-01

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 NaNO 3 , NaNO 2 , NH 4 Cl, 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. Copyright © 2016 Elsevier Inc. All rights reserved.

Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceans

DEFF Research Database (Denmark)

Christensen, Anne Munch; Faaborg-Andersen, S.; Ingerslev, Flemming

2007-01-01

Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications. primarily in the treatment of clinical depression. They are among the pharmaceuticals most often Prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds with an identi......Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications. primarily in the treatment of clinical depression. They are among the pharmaceuticals most often Prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds...... with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqeous as well as biological samples collected in the environment. In the present study, we tested the toxicities of five SSRIs (citalopram, fluoxetine, fluoxamine, paroxetine, and sertraline.......027 to 1.6 mg/L, and in daphnids, test EC50s ranged from 0.92 to 20 mg/L, with sertraline being one of the most toxic compounds. The test design and statistical analysis of results from mixture tests were based on isobole analysis. It was demonstrated that the mixture toxicity of the SSRIs in the two...

Photoenhanced Toxicity of Petroleum to Aquatic Invertebrates and Fish

Science.gov (United States)

Photoenhanced toxicity is a distinct mechanism of petroleum toxicity that is mediated by the interaction of solar radiation with specific polycyclic aromatic compounds in oil. Phototoxicity is observed as a twofold to greater than 1000-fold increase in chemical toxicity to aquati...

Compatibility of hydroxypropyl-β-cyclodextrin with algal toxicity bioassays

International Nuclear Information System (INIS)

Fai, Patricia Bi; Grant, Alastair; Reid, Brian J.

2009-01-01

Numerous reports have indicated that hydrophobic organic compound bioaccessibility in sediment and soil can be determined by extraction using aqueous hydroxypropyl-β-cyclodextrin (HPCD) solutions. This study establishes the compatibility of HPCD with Selenastrum capricornutum and assesses whether its presence influences the toxicity of reference toxicants. Algal growth inhibition (72 h) showed no significant (P > 0.05) difference at HPCD concentrations up to and including 20 mM. HPCD presence did not influence the toxicity of the inorganic reference toxicant (ZnSO 4 ), with IC50 values of 0.82 μM and 0.85 μM, in the presence and absence of HPCD (20 mM), respectively. However, HPCD presence (20 mM) reduced the toxicity of 2,4-dichlorophenol and the herbicides diuron and isoproturon. These reductions were attributed to inclusion complex formation between the toxicants and the HPCD cavity. Liberation of complexed toxicants, by sample manipulation prior to toxicity assessment, is proposed to provide a sensitive, high throughput, bioassay that reflects compound bioaccessibility. - Compatibility of the biomimetic HPCD extraction method with algal cell growth inhibition bioassays to assess toxicity of reference toxicants and environmental relevant herbicides

Compatibility of hydroxypropyl-{beta}-cyclodextrin with algal toxicity bioassays

Energy Technology Data Exchange (ETDEWEB)

Fai, Patricia Bi; Grant, Alastair [School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ (United Kingdom); Reid, Brian J. [School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ (United Kingdom)], E-mail: b.reid@uea.ac.uk

2009-01-15

Numerous reports have indicated that hydrophobic organic compound bioaccessibility in sediment and soil can be determined by extraction using aqueous hydroxypropyl-{beta}-cyclodextrin (HPCD) solutions. This study establishes the compatibility of HPCD with Selenastrum capricornutum and assesses whether its presence influences the toxicity of reference toxicants. Algal growth inhibition (72 h) showed no significant (P > 0.05) difference at HPCD concentrations up to and including 20 mM. HPCD presence did not influence the toxicity of the inorganic reference toxicant (ZnSO{sub 4}), with IC50 values of 0.82 {mu}M and 0.85 {mu}M, in the presence and absence of HPCD (20 mM), respectively. However, HPCD presence (20 mM) reduced the toxicity of 2,4-dichlorophenol and the herbicides diuron and isoproturon. These reductions were attributed to inclusion complex formation between the toxicants and the HPCD cavity. Liberation of complexed toxicants, by sample manipulation prior to toxicity assessment, is proposed to provide a sensitive, high throughput, bioassay that reflects compound bioaccessibility. - Compatibility of the biomimetic HPCD extraction method with algal cell growth inhibition bioassays to assess toxicity of reference toxicants and environmental relevant herbicides.

Patterns of presentation and clinical features of toxicity after reported use of ([2-aminopropyl]-2,3-dihydrobenzofurans), the 'benzofuran' compounds. A report from the United Kingdom National Poisons Information Service.

Science.gov (United States)

Kamour, Ashraf; James, David; Lupton, David J; Cooper, Gillian; Eddleston, Micheal; Vale, Allister; Thompson, John P; Thanacoody, Ruben; Hill, Simon L; Thomas, Simon H L

2014-12-01

To characterise the patterns of presentation and clinical features of toxicity following reported recreational use of benzofuran compounds ((2-aminopropyl)-2,3-dihydrobenzofurans) in the UK, as reported to the National Poisons Information Service (NPIS), and to compare clinical features of toxicity with those after reported mephedrone use. NPIS patient-specific telephone enquiries and user sessions for TOXBASE(®), the NPIS online information database, related to (2-aminopropyl)-2,3-dihydrobenzofurans and associated synonyms were reviewed from March 2009 to August 2013. These data were compared with those of mephedrone, the recreational substance most frequently reported to NPIS, collected over the same period. There were 63 telephone enquiries concerning 66 patients and 806 TOXBASE(®) user sessions regarding benzofuran compounds during the period of study. The first telephone enquiry was made in July 2010 and the highest numbers of enquiries were received in August 2010 (33 calls, 112 TOXBASE(®) sessions). Patients were predominantly male (82%) with a median age of 29 years; 9 reported co-ingestion of other substances. Comparing the 57 patients who reported ingesting benzofuran compounds alone with 315 patients ingesting mephedrone alone, benzofurans were more often associated with stimulant features, including tachycardia, hypertension, mydriasis, palpitation, fever, increased sweating, and tremor, (72% vs. 38%, odds ratio [OR] 4.2, 95% confidence interval [CI] 2.27-7.85, P < 0.0001) and mental health disturbances (58% vs. 38%, OR 2.3, 95% CI 1.29-4.07, P = 0.006). Other features reported after benzofuran compound ingestion included gastrointestinal symptoms (16%), reduced level of consciousness (9%), chest pain (7%), and creatinine kinase elevation (5%). Reported ingestion of benzofuran compounds is associated with similar toxic effects to those of amphetamines and cathinones. Mental health disturbances and stimulant features were reported more frequently

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

Science.gov (United States)

Tian, Dayong; Lin, Zhifen; Yin, Daqiang

2013-01-01

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.

Ability of Cu2+-montmorillonite to accept an toxic pollutants

International Nuclear Information System (INIS)

Janikova, V.; Jona, E.; Janik, R.; Pavlik, V.

2015-01-01

It is global problem that toxic pollutants are in the permanent contact to people through soil and water. Nowadays, it is important to eliminate these pollutants for future generations and to keep environment in the health condition. In relation to this article, aromatic organic compounds like benzene, phenol and aniline were chosen. These are used in various branches of industry, mainly in rubber industry or for production of dyes and in addition, phenol is commonly used in cosmetics or in food industry. Montmorillonite is clay mineral consisting of 2:1 sheets (tetrahedral:octahedral) and interlayer space where exchangeable cations and water molecules are present. Due to its structure, montmorillonite is able to accept some compounds or pollutants. This is the reason why it is mainly used as the covering material of radioactive waste in order to remove toxic pollutants. For investigation of toxic pollutants removing, XRD powder diffraction, infrared spectroscopy and thermal analysis were used. Our results show that Cu 2+ -montmorillonite is able to accept toxic benzene ring-based pollutants into interlayer. This mentioned ability can be proven on the basis of the investigation results relating to difference of interlayer distance, typical frequencies of -OH group or -NH 2 group, while these results were supplemented by thermal properties. (authors)

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

2016-01-01

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.

VARIATIONS IN REPRODUCTIVE TOXICANT IDENTIFICATION

Energy Technology Data Exchange (ETDEWEB)

Simmons, F

2008-05-13

Reproductive toxicants are a very important class of compounds. They present unique hazards to those of child bearing ages, perform their 'dirty work' using a wide variety of mechanisms on a number of different organs, and are regulatorily important. Because of all of this, properly identifying reproductive toxicants is important, but fraught with difficulty. In this paper we will describe types or reproductive toxicants, their importance, and both mistakes and good practices that people who are not experts in reproductive toxicology may use in their attempts to identify them. Additionally, this paper will focus on chemical reproductive toxicants and will not address biological agents that could affect reproductive toxicity although many principles outlined here could be applied to that endeavor.

Toxicity Identification Evaluation (TIE) of Belford Roxo industrial plant effluent and its contribution in water quality of downstream of Sarapui River, Iguacu River sub-basin, Baia da Guanabara Basin, RJ, Brazil

International Nuclear Information System (INIS)

Pires, Luiz Eduardo Botelho

2006-01-01

The quality of Belford Roxo Industrial Plant effluent and water from Sarapui River were evaluated with Daphnia similis, Ceriodaphnia dubia and Danio rerio acute and chronic toxicity tests. In association with the ecotoxicological monitoring, the Toxicity Identification Evaluation procedure were performed and the identification of the toxic compounds was possible. The Chloride ion was identified as the major toxic compound in the effluent with additional effects of Metals, Ammonium and Sulfide. For the Sarapui River, the compounds of Phosphorus and Nitrogen were identified as the major toxic compounds with addictive effects of Metals, Ammonium and Sulfide. Although the environmental impact estimation based on the effluent toxicity suggests a minor impact on the water quality of Sarapui River, this was already sufficiently contaminated to make impracticable the establishment of an aquatic community. The constant discharge of untreated sludge promotes the eutrophication of this water body and makes impossible the equilibrium of this ecosystem. (author)

Multipurpose Compound

Science.gov (United States)

1983-01-01

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.

APPROACH ON INTELLIGENT OPTIMIZATION DESIGN BASED ON COMPOUND KNOWLEDGE

Institute of Scientific and Technical Information of China (English)

Yao Jianchu; Zhou Ji; Yu Jun

2003-01-01

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.

Characterization of selected volatile organic compounds, polycyclic aromatic hydrocarbons and carbonyl compounds at a roadside monitoring station

Science.gov (United States)

Ho, K. F.; Lee, S. C.; Chiu, Gloria M. Y.

Volatile organic compounds (VOCs), PAHs and carbonyl compounds are the major toxic components in Hong Kong. Emissions from motor vehicles have been one of the primary pollution sources in the metropolitan areas throughout Hong Kong for a long time. A 1-yr monitoring program for VOCs, PAHs and carbonyl compounds had been performed at a roadside urban station at Hong Kong Polytechnic University in order to determine the variations and correlations of each selected species (VOCs, PAHs and carbonyl compounds). This study is aimed to analyze toxic volatile organic compounds (benzene, toluene, ethylbenzene and xylene), two carbonyl compounds (formaldehyde, acetaldehyde), and selective polycyclic aromatic hydrocarbons. The monitoring program started from 16 April 1999 to 30 March 2000. Ambient VOC concentrations, many of which originate from the same sources as particulate PAHs and carbonyls compounds, show significant quantities of benzene, toluene and xylenes. Correlations and multivariate analysis of selected gaseous and particulate phase organic pollutants were performed. Source identification by principle component analysis and hierarchical cluster analysis allowed the identification of four sources (factors) for the roadside monitoring station. Factor 1 represents the effect of diesel vehicle exhaust. Factor 2 shows the contribution of aromatic compounds. Factor 3 explains photochemical products—formaldehyde and acetaldehyde. Factor 4 explains the effect of gasoline vehicle exhaust.

TOXICOPHORES AND QUANTITATIVE STRUCTURE -TOXICITY RELATIONSHIPS FOR SOME ENVIRONMENTAL POLLUTANTS

Directory of Open Access Journals (Sweden)

N. N. Gorinchoy

2008-06-01

Full Text Available The electron-conformational (EC method is employed to reveal the toxicophore and to predict aquatic toxicity quantitatively using as a training set a series of 51 compounds that have aquatic toxicity to fish. By performing conformational analysis (optimization of geometries of the low-energy conformers by the PM3 method and electronic structure calculations (by ab initio method corrected within the SM54/PM3 solvatation model, the Electron-Conformational Matrix of Congruity (ECMC was constructed for each conformation of these compounds. The toxicophore defined as the EC sub-matrix of activity (ECSA, a sub-matrix with matrix elements common to all the active compounds under consideration within minimal tolerances, is determined by an iterative procedure of comparison of their ECMC’s, gradually minimizing the tolerances. Starting with only the four most toxic compounds, their ECSA (toxicophore was found to consists of a 4x4 matrix (four sites with certain electronic and topologic characteristics which was shown to be present in 17 most active compounds. A structure-toxicity correlation between three toxicophore parameters and the activities of these 17 compounds with R2=0.94 was found. It is shown that the same toxicophore with larger tolerances satisfies the compounds with les activity, thus explicitly demonstrating how the activity is controlled by the tolerances quantitatively and which atoms (sites are most flexible in this respect. This allows for getting slightly different toxicophores for different levels of activity. For some active compounds that have no toxicophore a bimolecular mechanism of activity is suggested. Distinguished from other QSAR methods, no arbitrary descriptors and no statistics are involved in this EC structure-activity investigation.

High-content, high-throughput screening for the identification of cytotoxic compounds based on cell morphology and cell proliferation markers.

Directory of Open Access Journals (Sweden)

Heather L Martin

Full Text Available Toxicity is a major cause of failure in drug discovery and development, and whilst robust toxicological testing occurs, efficiency could be improved if compounds with cytotoxic characteristics were identified during primary compound screening. The use of high-content imaging in primary screening is becoming more widespread, and by utilising phenotypic approaches it should be possible to incorporate cytotoxicity counter-screens into primary screens. Here we present a novel phenotypic assay that can be used as a counter-screen to identify compounds with adverse cellular effects. This assay has been developed using U2OS cells, the PerkinElmer Operetta high-content/high-throughput imaging system and Columbus image analysis software. In Columbus, algorithms were devised to identify changes in nuclear morphology, cell shape and proliferation using DAPI, TOTO-3 and phosphohistone H3 staining, respectively. The algorithms were developed and tested on cells treated with doxorubicin, taxol and nocodazole. The assay was then used to screen a novel, chemical library, rich in natural product-like molecules of over 300 compounds, 13.6% of which were identified as having adverse cellular effects. This assay provides a relatively cheap and rapid approach for identifying compounds with adverse cellular effects during screening assays, potentially reducing compound rejection due to toxicity in subsequent in vitro and in vivo assays.

Toxicity profile of choline chloride-based deep eutectic solvents for fungi and Cyprinus carpio fish.

Science.gov (United States)

Juneidi, Ibrahim; Hayyan, Maan; Mohd Ali, Ozair

2016-04-01

An investigation on the toxicological assessment of 10 choline chloride (ChCl)-based deep eutectic solvents (DESs) towards four fungi strains and Cyprinus carpio fish was conducted. ChCl was combined with materials from different chemical groups such as alcohols, sugars, acids and others to form DESs. The study was carried out on the individual DES components, their aqueous mixture before DES formation and their formed DESs. The agar disc diffusion method was followed to investigate their toxicity on four fungi strains selected as a model of eukaryotic microorganisms (Phanerochaete chrysosporium, Aspergillus niger, Lentinus tigrinus and Candida cylindracea). Among these DESs, ChCl:ZnCl2 exhibited the highest inhibition zone diameter towards the tested fungi growth in vitro, followed by the acidic group (malonic acid and p-toluenesulfonic acid). Another study was conducted to test the acute toxicity and determine the lethal concentration at 50 % (LC50) of the same DESs on C. carpio fish. The inhibition range and LC50 of DESs were found to be different from their individual components. DESs were found to be less toxic than their mixture or individual components. The LC50 of ChCl:MADES is much higher than that of ChCl:MAMix. Moreover, the DESs acidic group showed a lower inhibition zone on fungi growth. Thus, DESs should be considered as new components with different physicochemical properties and toxicological profiles, and not merely compositions of compounds.

Triorganotin as a compound with potential reproductive toxicity in mammals

Directory of Open Access Journals (Sweden)

V.S. Delgado Filho

2011-09-01

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.

Fluorescence-based assay as a new screening tool for toxic chemicals

Science.gov (United States)

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

2016-09-01

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.

A fluorescence-based rapid screening assay for cytotoxic compounds

International Nuclear Information System (INIS)

Montoya, Jessica; Varela-Ramirez, Armando; Estrada, Abril; Martinez, Luis E.; Garza, Kristine; Aguilera, Renato J.

2004-01-01

A simple fluorescence-based assay was developed for the rapid screening of potential cytotoxic compounds generated by combinatorial chemistry. The assay is based on detection of nuclear green fluorescent protein (GFP) staining of a human cervical cancer cell line (HeLa) carrying an integrated histone H2B-GFP fusion gene. Addition of a cytotoxic compound to the HeLa-GFP cells results in the eventual degradation of DNA and loss of the GFP nuclear fluorescence. Using this assay, we screened 11 distinct quinone derivatives and found that several of these compounds were cytotoxic. These compounds are structurally related to plumbagin an apoptosis-inducing naphthoquinone isolated from Black Walnut. In order to determine the mechanism by which cell death was induced, we performed additional experiments with the most cytotoxic quinones. These compounds were found to induce morphological changes (blebbing and nuclear condensation) consistent with induction of apoptosis. Additional tests revealed that the cytotoxic compounds induce both necrotic and apoptotic modes of death

About neutralization of the toxic waste of galvanic production

International Nuclear Information System (INIS)

Akhmetzhanova, Z.Kh.; Samatov, I.B.

1996-01-01

The nature of heavy metals ions migration to environment from the galvanic production is considered in the article. The method of toxic precipitations transformation to non-toxic ones is proposed. The essence of stabilization method of heavy metals hydroxides precipitations consists in transformation of galvanic precipitations mixture to same metals ferrites mixture. The reaction has followed in oxygen medium under heating of galvanic precipitations from 70 up 90 deg C. Before heating the precipitation have acid medium, after temperature treatment the medium turn to the neutral one. These compounds are presented as ferrite class and can be serve as base for various pigments. (author)

Impacts of UV radiation and photomodification on the toxicity of PAHs to the higher plant Lemna gibba (duckweed)

International Nuclear Information System (INIS)

Huang, X.D.; Dixon, D.G.; Greenberg, B.M.

1993-01-01

The toxicity of polycyclic aromatic hydrocarbons (PAHs) can be enhanced by both biotic and abiotic processes. This is exemplified by light, which, by virtue of the extensive π-orbital systems of PAHs, can be a major factor in PAH toxicity. Light activation of PAHs is known to occur via photosensitization reactions (generation of singlet oxygen and superoxide) and potentially by photomodification of the chemicals (photooxidation and/or photolysis) to more toxic species. To examine the modes of PAH action in the light and determine if the photomodified compounds are hazardous, we investigated the photoinduced toxicity of anthracene, phenanthrene and benzo[a]pyrene to the aquatic higher plant Lemna gibba (a duckweed). Toxicity end points were inhibition of growth and extent of chlorosis. Light did indeed activate the phytotoxicity of PAHs, with UV radiation more effective than visible light. Dose-response curves based on chemical concentration and light intensity revealed the order of phytotoxic strength to be anthracene > phenanthrene > benzo[a]pyrene. To explore whether photomodified PAHs were contributing to toxicity, the chemicals were irradiated before toxicity testing. The rates of photomodification of the three PAHs were rapid (half-lives in hours), and the relative velocities were coincident with the order of toxic strength. Furthermore, the photomodified PAHs were more hazardous to Lemna than the intact compounds. Because interpretations of the potential impacts of PAHs in the environment are based mostly on measurements of the structurally intact chemicals, the severity of PAH hazards is possibly underestimated

Aluminium toxicity tolerance in crop plants: Present status of research

African Journals Online (AJOL)

... tolerance of which genes of the Aluminium-activated malate transporter (ALMT) and multidrug and toxic compound extrusion (MATE) families are prominent. In this review, the progress of research in identifying aluminium toxicity tolerant genes is discussed. Keywords: Aluminium toxicity, soil acidity, hydroponic screening, ...

Toxicity of Pesticides. Agrichemical Fact Sheet 2.

Science.gov (United States)

Hock, Winand K.

This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

Sulphate, more than a nutrient, protects the microalga Chlamydomonas moewusii from cadmium toxicity

Energy Technology Data Exchange (ETDEWEB)

Mera, Roi; Torres, Enrique, E-mail: torres@udc.es; Abalde, Julio

2014-03-01

Highlights: • Sulphate effect on cadmium toxicity in the microalga Chlamydomonas moewusii Gerloff. • Cadmium increases the sulphur requirements in Chlamydomonas moewusii. • Kinetic coefficients for sulphate utilization and cadmium effect on them. • Sulphate and cadmium influence on the biosynthesis of low-molecular mass thiols. • Cadmium toxicity reduction by sulphate due to higher biosynthesis of thiols. - Abstract: Sulphur is an essential macroelement that plays important roles in living organisms. The thiol rich sulphur compounds, such as cysteine, γ-Glu–Cys, glutathione and phytochelatins participate in the tolerance mechanisms against cadmium toxicity. Plants, algae, yeasts and most prokaryotes cover their demand for reduced sulphur by reduction of inorganic sulphate. The aim of this study was to investigate, using a bifactorial experimental design, the effect of different sulphate concentrations in the nutrient solution on cadmium toxicity in the freshwater microalga Chlamydomonas moewusii. Cell growth, kinetic parameters of sulphate utilization and intracellular concentrations of low-molecular mass thiol compounds were determined. A mathematical model to describe the growth of this microalga based on the effects of sulphate and cadmium was obtained. An ANOVA revealed an interaction between them, 16% of the effect sizes was explained by this interaction. A higher amount of sulphate in the culture medium allowed a higher cadmium tolerance due to an increase in the thiol compound biosynthesis. The amount of low-molecular mass thiol compounds, mainly phytochelatins, synthesized by this microalga was significantly dependent on the sulphate and cadmium concentrations; the higher phytochelatin content was obtained in cultures with 4 mg Cd/L and 1 mM sulphate. The maximum EC{sub 50} value (based on nominal cadmium concentration) reached for this microalga was 4.46 ± 0.42 mg Cd/L when the sulphate concentration added to the culture medium was also 1 m

Mechanistic Investigations Into the Developmental Toxicity of Nitrated and Heterocyclic PAHs

Science.gov (United States)

Chlebowski, Anna C.; Garcia, Gloria R.; La Du, Jane K.; Bisson, William H.; Truong, Lisa; Massey Simonich, Staci L.

2017-01-01

Abstract Nitrated polycyclic aromatic hydrocarbons (NPAHs) and heterocyclic PAHs (HPAHs) are recognized environmental pollutants. However, the health risks of NPAHs and HPAHs to humans and environmental systems are not well-studied. The developmental zebrafish (Danio rerio) model was used to evaluate the toxicity of a structurally diverse set of 27 NPAHs and 10 HPAHs. The individual activity of each compound towards the aryl hydrocarbon receptor (AHR), including the role of the AHR in observed toxicity, and genetic markers of oxidative stress and cardiac toxicity were evaluated. Zebrafish embryos were exposed from 6 to 120 hours post fertilization (hpf), to a broad concentration range of individual compounds, and evaluated for 22 developmental endpoints. The potential role of AHR was determined using the transgenic Tg(cyp1a:nls-egfp) reporter zebrafish line. All compounds were screened computationally through molecular docking using a previously developed AHR models of zebrafish isoforms 1A, 1B, and 2. Some compounds did not induce observable developmental toxic responses, whereas others produced statistically significant concentration-dependent toxicity. The tested compounds also exhibited a range of predicted AHR binding and cyp1a/GFP induction patterns, including cyp1a expression in the liver, vasculature, skin, and yolk, which we determined to be due to distinct isoforms of the AHR, using morpholino oligonucleotide knockdown. Furthermore, we investigated mRNA expression of oxidative and cardiac stress genes at 48 and 120 hpf, which indicated several potential mechanisms-of-action for NPAHs. Overall, we observed a range of developmental toxicities, cyp1a/GFP expression patterns, and gene expression profiles, suggestive of several potential mechanisms of action. PMID:28186253

Review Article. Organochlorine pesticides, their toxic effects on living organisms and their fate in the environment

Directory of Open Access Journals (Sweden)

Jayaraj Ravindran

2016-12-01

Full Text Available Organochlorine (OC pesticides are synthetic pesticides widely used all over the world. They belong to the group of chlorinated hydrocarbon derivatives, which have vast application in the chemical industry and in agriculture. These compounds are known for their high toxicity, slow degradation and bioaccumulation. Even though many of the compounds which belong to OC were banned in developed countries, the use of these agents has been rising. This concerns particularly abuse of these chemicals which is in practice across the continents. Though pesticides have been developed with the concept of target organism toxicity, often non-target species are affected badly by their application. The purpose of this review is to list the major classes of pesticides, to understand organochlorine pesticides based on their activity and persistence, and also to understand their biochemical toxicity.

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

Science.gov (United States)

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparative toxicity of two azadirachtin-based neem pesticides to Daphnia pulex.

Science.gov (United States)

Goktepe, Ipek; Plhak, Leslie C

2002-01-01

Azadirachtin (AZA)-based pesticides (Neemix and Bioneem) demonstrated toxicity in 48-h nonrenewal toxicity assays using Daphnia pulex at levels that were comparable with several organophosphate pesticides. The median lethal concentration (LC50) values for the two neem pesticides were found to be 0.028 and 0.033 microl/ml, respectively. The LC50 value for nonformulated (95% pure) AZA was determined to be 0.382 microg AZA/ml. Neemix and Bioneem were exposed to air and northern sky daylight in a light box at 24 and 37 degrees C for 1, 3, 6, and 9 d. Standard 48-h acute toxicity tests were used to determine the effect of aging in these dry environmental conditions. Neemix and Bioneem were also fractionated into volatile and nonvolatile fractions, and the toxicity of each was tested. Compared with Neemix, Bioneem remained toxic longer when exposed to light and air at 37 degrees C, indicating that this pesticide may be less prone to environmental degradation. When fractionated, the nonvolatile fractions for both pesticides exhibited significantly lower LC50 values than the full formulations. These results suggest that, depending on the application rate and environmental fate, AZA-based pesticides may have direct adverse effects on aquatic organisms and that the toxicity and stability of formulated pesticides depend on factors other than only the AZA concentration.

Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

Science.gov (United States)

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

2017-01-01

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...

Vanadium Compounds as PTP Inhibitors

Directory of Open Access Journals (Sweden)

Elsa Irving

2017-12-01

Full Text Available Phosphotyrosine signaling is regulated by the opposing actions of protein tyrosine kinases (PTKs and protein tyrosine phosphatases (PTPs. Here we discuss the potential of vanadium derivatives as PTP enzyme inhibitors and metallotherapeutics. We describe how vanadate in the V oxidized state is thought to inhibit PTPs, thus acting as a pan-inhibitor of this enzyme superfamily. We discuss recent developments in the biological and biochemical actions of more complex vanadium derivatives, including decavanadate and in particular the growing number of oxidovanadium compounds with organic ligands. Pre-clinical studies involving these compounds are discussed in the anti-diabetic and anti-cancer contexts. Although in many cases PTP inhibition has been implicated, it is also clear that many such compounds have further biochemical effects in cells. There also remain concerns surrounding off-target toxicities and long-term use of vanadium compounds in vivo in humans, hindering their progress through clinical trials. Despite these current misgivings, interest in these chemicals continues and many believe they could still have therapeutic potential. If so, we argue that this field would benefit from greater focus on improving the delivery and tissue targeting of vanadium compounds in order to minimize off-target toxicities. This may then harness their full therapeutic potential.

Behavioral toxicity of selected radioprotectors

Science.gov (United States)

Landauer, M. R.; Davis, H. D.; Kumar, K. S.; Weiss, J. F.

1992-10-01

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

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)

2010-04-15

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.)

Compounds in dictionary-based Cross-language information retrieval_revised

Directory of Open Access Journals (Sweden)

2002-01-01

Full Text Available Compound words form an important part of natural language. From the cross-lingual information retrieval (CLIR point of view it is important that many natural languages are highly productive with compounds, and translation resources cannot include entries for all compounds. Also, compounds are often content bearing words in a sentence. In Swedish, German and Finnish roughly one tenth of the words in a text prepared for information retrieval purposes are compounds. Important research questions concerning compound handling in dictionary-based cross-language information retrieval are 1 compound splitting into components, 2 normalisation of components, 3 translation of components and 4 query structuring for compounds and their components in the target language. The impact of compound processing on the performance of the cross-language information retrieval process is evaluated in this study and the results indicate that the effect is clearly positive.

Toxicity ranking and toxic mode of action evaluation of commonly used agricultural adjuvants on the basis of bacterial gene expression profiles.

Directory of Open Access Journals (Sweden)

Ingrid Nobels

Full Text Available The omnipresent group of pesticide adjuvants are often referred to as "inert" ingredients, a rather misleading term since consumers associate this term with "safe". The upcoming new EU regulation concerning the introduction of plant protection products on the market (EC1107/2009 includes for the first time the demand for information on the possible negative effects of not only the active ingredients but also the used adjuvants. This new regulation requires basic toxicological information that allows decisions on the use/ban or preference of use of available adjuvants. In this study we obtained toxicological relevant information through a multiple endpoint reporter assay for a broad selection of commonly used adjuvants including several solvents (e.g. isophorone and non-ionic surfactants (e.g. ethoxylated alcohols. The used assay allows the toxicity screening in a mechanistic way, with direct measurement of specific toxicological responses (e.g. oxidative stress, DNA damage, membrane damage and general cell lesions. The results show that the selected solvents are less toxic than the surfactants, suggesting that solvents may have a preference of use, but further research on more compounds is needed to confirm this observation. The gene expression profiles of the selected surfactants reveal that a phenol (ethoxylated tristyrylphenol and an organosilicone surfactant (ethoxylated trisiloxane show little or no inductions at EC(20 concentrations, making them preferred surfactants for use in different applications. The organosilicone surfactant shows little or no toxicity and good adjuvant properties. However, this study also illustrates possible genotoxicity (induction of the bacterial SOS response for several surfactants (POEA, AE, tri-EO, EO FA and EO NP and one solvent (gamma-butyrolactone. Although the number of compounds that were evaluated is rather limited (13, the results show that the used reporter assay is a promising tool to rank commonly

Isoniazid release from suppositories compounded with selected bases.

Science.gov (United States)

Hudson, Kristofer C; Asbill, C Scott; Webster, Andrew A

2007-01-01

There is an increasing need for an alternative route of isoniazid adminstration for prophylaxis and treatment of tuberculosis in children. The purpose of this study is to evaluate the in vitro release of isoniazid from extemporaneously compounded isoniazid suppositories with a goal of optimizing the suppository dosage form for this indication. Suppositories were compounded using three different base formulations (cocoa butter, Witepsol H15 Base F, and a combination of polyethylene glycols 3350, 1000, and 400). The release profiles of six compounded suppositories with isoniazid (100 mg) were tested with a United States Pharmacopeial Convention-approved dissolution apparatus. Isoniazid concentrations at predetermined time points were determined using high-performance liquid chromatographic analysis. The results show that drug release from the water-solutble base (mixed polyethylene glycols) was significantly greater than that from the lipophilic bases (cocoa butter and Witepsol H15). The percentage of isoniazid release form the polyethylene glycol suppository formulation (70 +/- 1.4 mg/mL) was greater than that from the cocoa butter (55 +/- 1.1 mg/mL) and Witepsol H15 Base F (18 +/- 0.36 mg/mL) suppository formulations.

Models for the field-based toxicity of copper and zinc salts to wheat in 11 Australian soils and comparison to laboratory-based models

International Nuclear Information System (INIS)

Warne, Michael St.J.; Heemsbergen, Diane; McLaughlin, Mike; Bell, Mike; Broos, Kris; Whatmuff, Mark; Barry, Glenn; Nash, David; Pritchard, Deb; Penney, Nancy

2008-01-01

Laboratory-based relationships that model the phytotoxicity of metals using soil properties have been developed. This paper presents the first field-based phytotoxicity relationships. Wheat (Triticum aestivum L.) was grown at 11 Australian field sites at which soil was spiked with copper (Cu) and zinc (Zn) salts. Toxicity was measured as inhibition of plant growth at 8 weeks and grain yield at harvest. The added Cu and Zn EC10 values for both endpoints ranged from approximately 3 to 4760 mg/kg. There were no relationships between field-based 8-week biomass and grain yield toxicity values for either metal. Cu toxicity was best modelled using pH and organic carbon content while Zn toxicity was best modelled using pH and the cation exchange capacity. The best relationships estimated toxicity within a factor of two of measured values. Laboratory-based phytotoxicity relationships could not accurately predict field-based phytotoxicity responses. - Field-based toxicity of Cu and Zn to wheat can be modelled using soil properties. Laboratory-based models should not be used to estimate toxicity in the field

Toxicity and antioxidant activity of flavonoids from Lonchocarpus filipes root bark

International Nuclear Information System (INIS)

Santos, Erica L.; Costa, Emmanoel V.; Marques, Francisco A.; Vaz, Nelissa P.; Maia, Beatriz Helena L.N. Sales; Magalhes, Eva G.; Tozzi, Ana Maria A.

2009-01-01

The phytochemical investigation of dichloromethane extract from root bark of Lonchocarpus filipes Benth (Leguminosae) afforded four flavonoids including three dibenzoylmethane derivatives rarely found in nature. The structures were established based on their spectral data ( 1 H and 13 C NMR, 2D-NMR) as being: lanceolatin B (1), pongamol (2), (E)-7-O-methylpongamol (3) and (E)-9-O-methylpongamol (4). Compound (4) is described herein for the first time as a natural product. The extracts and the isolated compounds (1), (2) and (3) displayed high toxicity in the brine shrimp lethality assay. Only compound (2) showed antioxidant activity using a DPPH radical scavenging assay. This is the first report on the phytochemical study of Lonchocarpus filipes. (author)

Degradation and toxicity assessment of sulfamethoxazole and chlortetracycline using electron beam, ozone and UV

International Nuclear Information System (INIS)

Kim, Tae-Hun; Kim, Sang Don; Kim, Hyun Young; Lim, Seung Joo; Lee, Myunjoo; Yu, Seungho

2012-01-01

Highlights: ► The degradation efficiency and trends for antibiotics were different between AOPs. ► The toxicities of target antibiotics were mainly affected by parent compounds. ► E-beam was electrically more energy efficient than ozone and UV-C. ► Application of AOPs should be considered according to the types of pharmaceuticals. - Abstract: Recently, the occurrence of antibiotics in sewage treatment plant effluent, as well as drinking water, has raised concern about their potential impacts on the environment and public health. Antibiotics are found in surface and ground waters, which indicate their ineffective removal by conventional wastewater treatment processes. Therefore, advanced oxidation processes (AOPs) have received considerable attention for the removal of antibiotics. This study was conducted to evaluate the degradation and mineralization of antibiotics (sulfamethoxazole and chlortetracycline) using an electron beam, ozone and UV, and the change of toxicity. Also, the electrical energy consumption based on the EE/O parameter (the electrical energy required per order of pollutants removal in 1 m 3 wastewater) was used to quantify the energy cost associated with the different AOPs (electron beam, ozone and UV) for the degradation of antibiotics. The results showed that an electron beam effective for the removals of both sulfamethoxazole and chlortetracycline in aqueous solutions. However, degradation of the target compounds by ozone and UV showed different trends. The oxidation efficiency of each organic compound was very dependent upon the AOP used. Algal toxicity was significantly reduced after each treatment. However, based on the electrical energy, the electron beam was more efficient than ozone and UV. Electron beam treatment could be an effective and safe method for the removal of antibiotic compounds.

Humic Acids as Therapeutic Compounds in Lead Intoxication.

Science.gov (United States)

Krempaská, Klára; Vaško, Ladislav; Vašková, Janka

2016-01-01

The toxicity of lead and its compounds is well known, causing anemia by inhibiting the synthesis of porphyrins. The neurotoxic effects, particularly in the young, alter the structure of cell membranes and DNA. Chronic exposure to lead has adverse effects on the body by disrupting the mechanisms of energy production and tissue damage, in particular in its links with thiol groups and competition for binding sites with zinc. This review is therefore a description of the mechanism of lead toxicity as well as of possible interventions for the detoxification of the body. Part of the clinical intervention is the provision of chelates that form insoluble complexes with lead and eliminate the load in tissues. Most of these chelating agents have a number of side effects. It is therefore not surprising that active compounds with distinctive antioxidant and chelating properties are being sought after. The possibility of administering lower amounts, and the corresponding decrease in side effects, would be important for clinical practice. Both prospective studies and our initial studies on humic acids have highlighted positive effects based on their antioxidant and chelating properties.

Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

Science.gov (United States)

Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

2018-05-10

Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Performance investigation of low-toxic organic corrosion inhibitors in amine treating unit

International Nuclear Information System (INIS)

Veawab, A.; Tanthapanichakoon, W.

2003-01-01

Amine treating unit is constantly subject to severe corrosion problems leading to extra expenditure and operational limitations. Heavy-metal vanadium compounds are extensively used as corrosion inhibitors to suppress the severe corrosion to an acceptable level. In recent years, the fact that these vanadium compounds are inherently toxic and can potentially pose adverse impacts on the human health and the environment has brought about environmental awareness that causes their uses costly due to the difficulty in waste disposal. To respond to the environmental concern and reduce cost of waste disposal as well as prepare for more stringent regulations for chemical uses, the development of low-toxic corrosion inhibitors is necessary. This work therefore focuses on an investigation of inhibition performance of a number of organic and inorganic compounds that have relatively low toxicity in comparison with conventional inhibitors. The performance evaluation was carried out through corrosion experiments using carbon steel specimens. The experiments were done in 3 and 5 kmol/m 3 monoethanolamine (MEA) solution saturated with CO 2 at 80 o C. It was found that several tested compounds have potential to be effective low-toxic corrosion inhibitors. The promising compounds provide reasonable and in some cases comparable protection performance to the conventional inhibitor. (author)

In vitro screening of organotin compounds and sediment extracts for cytotoxicity to fish cells.

Science.gov (United States)

Giltrap, Michelle; Macken, Ailbhe; McHugh, Brendan; McGovern, Evin; Foley, Barry; Davoren, Maria

2011-01-01

The present study reports an in vitro screening method for contaminants in sediment samples utilizing an RTG-2 cell line. This technique integrates cytotoxicity testing with analytical chemistry with the aim of achieving a toxicity evaluation of the sediment sample. The toxic effect of individual organotin (OT) compounds and their presence in the sediment sample is the focus of the present study; however, other contaminants are also discussed. The following OT compounds: tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenyltin (DPT), and a sediment solvent extract are exposed to the RTG-2 fish cell line. Both the alamar blue (AB) and neutral red (NR) assays are used to assess cytotoxicity after 24-h and 96-h exposure. Methodology for preparation of a sediment solvent extract suitable for biological testing and analytical determination is also described. With the RTG-2 cells, the AB and NR assays had comparable sensitivity for each individual OT compound exposure after 24 h, with TPT being the most toxic compound tested. The individual OT compound concentrations required to induce a 50% toxic effect on the cells (369 ng ml⁻¹ TBT, 1,905 ng ml⁻¹ DBT) did not equate to the concentrations of these contaminants present in the sediment extract that induced a 50% effect on the cells (294 ng ml⁻¹ TBT, 109 ng ml⁻¹ DBT). The solvent extract therefore exhibited a greater toxicity, and this suggests that the toxic effects observed were not due to OT compounds alone. The presence of other contaminants in the solvent extract is confirmed with chemical analysis, warranting further toxicity testing of contaminant mixtures and exposure to the cell line to further elucidate a complete toxicity evaluation. © 2010 SETAC.

Airborne uranium, its concentration and toxicity in uranium enrichment facilities

International Nuclear Information System (INIS)

Thomas, J.; Mauro, J.; Ryniker, J.; Fellman, R.

1979-02-01

The release of uranium hexafluoride and its hydrolysis products into the work environment of a plant for enriching uranium by means of gas centrifuges is discussed. The maximum permissible mass and curie concentration of airborne uranium (U) is identified as a function of the enrichment level (i.e., U-235/total U), and chemical and physical form. A discussion of the chemical and radiological toxicity of uranium as a function of enrichment and chemical form is included. The toxicity of products of UF 6 hydrolysis in the atmosphere, namely, UO 2 F 2 and HF, the particle size of toxic particulate material produced from this hydrolysis, and the toxic effects of HF and other potential fluoride compounds are also discussed. Results of an investigation of known effects of humidity and temperature on particle size of UO 2 F 2 produced by the reaction of UF 6 with water vapor in the air are reported. The relationship of the solubility of uranium compounds to their toxic effects was studied. Identification and discussion of the standards potentially applicable to airborne uranium compounds in the working environment are presented. The effectiveness of High Efficiency Particulate (HEPA) filters subjected to the corrosive environment imposed by the presence of hydrogen fluoride is discussed

Influence of S. mutans on base-metal dental casting alloy toxicity.

Science.gov (United States)

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

2013-01-01

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 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.

Adsorption of volatile organic compounds by pecan shell- and almond shell-based granular activated carbons.

Science.gov (United States)

Bansode, R R; Losso, J N; Marshall, W E; Rao, R M; Portier, R J

2003-11-01

The objective of this research was to determine the effectiveness of using pecan and almond shell-based granular activated carbons (GACs) in the adsorption of volatile organic compounds (VOCs) of health concern and known toxic compounds (such as bromo-dichloromethane, benzene, carbon tetrachloride, 1,1,1-trichloromethane, chloroform, and 1,1-dichloromethane) compared to the adsorption efficiency of commercially used carbons (such as Filtrasorb 200, Calgon GRC-20, and Waterlinks 206C AW) in simulated test medium. The pecan shell-based GACs were activated using steam, carbon dioxide or phosphoric acid. An almond shell-based GAC was activated with phosphoric acid. Our results indicated that steam- or carbon dioxide-activated pecan shell carbons were superior in total VOC adsorption to phosphoric acid-activated pecan shell or almond shell carbons, inferring that the method of activation selected for the preparation of activated carbons affected the adsorption of VOCs and hence are factors to be considered in any adsorption process. The steam-activated, pecan shell carbon adsorbed more total VOCs than the other experimental carbons and had an adsorption profile similar to the two coconut shell-based commercial carbons, but had greater adsorption than the coal-based commercial carbon. All the carbons studied adsorbed benzene more effectively than the other organics. Pecan shell, steam-activated and acid-activated GACs showed higher adsorption of 1,1,1-trichloroethane than the other carbons studied. Multivariate analysis was conducted to group experimental carbons and commercial carbons based on their physical, chemical, and adsorptive properties. The results of the analysis conclude that steam-activated and acid-activated pecan shell carbons clustered together with coal-based and coconut shell-based commercial carbons, thus inferring that these experimental carbons could potentially be used as alternative sources for VOC adsorption in an aqueous environment.

Accounting for dissociation and photolysis: a review of the algal toxicity of triclosan.

Science.gov (United States)

Roberts, Jayne; Price, Oliver R; Bettles, Nicola; Rendal, Cecilie; van Egmond, Roger

2014-11-01

Triclosan, an antimicrobial agent commonly used in down-the-drain consumer products, is toxic to freshwater microalgae. However, the rapid photolysis and pH-dependent dissociation of this compound may give rise to uncertainty in growth inhibition tests with freshwater microalgae, if these are not well characterized. Methods are presented to minimize these uncertainties by stabilizing pH with an organic buffering agent (Bis-Tris) and by the application of ultraviolet (UV) covers to remove UV wavelengths. Toxicity tests with these methods were in compliance with the validity criteria of the Organisation for Economic Co-operation and Development test 201, and no negative effects were seen in controls relative to the unmodified method. The methods were used for toxicity tests with triclosan at pH levels of 7.0, 8.0, and 8.5, yielding effective concentration, 10% values of 0.5 µg/L, 0.6 µg/L, and 12.1 µg/L, respectively. The observed change in toxicity with pH was proportional to the change in bioconcentration factor (BCF) as calculated using the cell model (a dynamic flux model based on the Fick-Nernst-Planck equations, in this case parameterized for an algal cell). Effect concentrations produced with the methods presented in the present study offer robust data on which to base risk assessment, and it is suggested that similar approaches be used to minimize uncertainty when other compounds that dissociate and photolyse are tested. © 2014 SETAC.

In silico toxicology: comprehensive benchmarking of multi-label classification methods applied to chemical toxicity data

KAUST Repository

Raies, Arwa B.

2017-12-05

One goal of toxicity testing, among others, is identifying harmful effects of chemicals. Given the high demand for toxicity tests, it is necessary to conduct these tests for multiple toxicity endpoints for the same compound. Current computational toxicology methods aim at developing models mainly to predict a single toxicity endpoint. When chemicals cause several toxicity effects, one model is generated to predict toxicity for each endpoint, which can be labor and computationally intensive when the number of toxicity endpoints is large. Additionally, this approach does not take into consideration possible correlation between the endpoints. Therefore, there has been a recent shift in computational toxicity studies toward generating predictive models able to predict several toxicity endpoints by utilizing correlations between these endpoints. Applying such correlations jointly with compounds\\' features may improve model\\'s performance and reduce the number of required models. This can be achieved through multi-label classification methods. These methods have not undergone comprehensive benchmarking in the domain of predictive toxicology. Therefore, we performed extensive benchmarking and analysis of over 19,000 multi-label classification models generated using combinations of the state-of-the-art methods. The methods have been evaluated from different perspectives using various metrics to assess their effectiveness. We were able to illustrate variability in the performance of the methods under several conditions. This review will help researchers to select the most suitable method for the problem at hand and provide a baseline for evaluating new approaches. Based on this analysis, we provided recommendations for potential future directions in this area.

In silico toxicology: comprehensive benchmarking of multi-label classification methods applied to chemical toxicity data

KAUST Repository

Raies, Arwa B.; Bajic, Vladimir B.

2017-01-01

One goal of toxicity testing, among others, is identifying harmful effects of chemicals. Given the high demand for toxicity tests, it is necessary to conduct these tests for multiple toxicity endpoints for the same compound. Current computational toxicology methods aim at developing models mainly to predict a single toxicity endpoint. When chemicals cause several toxicity effects, one model is generated to predict toxicity for each endpoint, which can be labor and computationally intensive when the number of toxicity endpoints is large. Additionally, this approach does not take into consideration possible correlation between the endpoints. Therefore, there has been a recent shift in computational toxicity studies toward generating predictive models able to predict several toxicity endpoints by utilizing correlations between these endpoints. Applying such correlations jointly with compounds' features may improve model's performance and reduce the number of required models. This can be achieved through multi-label classification methods. These methods have not undergone comprehensive benchmarking in the domain of predictive toxicology. Therefore, we performed extensive benchmarking and analysis of over 19,000 multi-label classification models generated using combinations of the state-of-the-art methods. The methods have been evaluated from different perspectives using various metrics to assess their effectiveness. We were able to illustrate variability in the performance of the methods under several conditions. This review will help researchers to select the most suitable method for the problem at hand and provide a baseline for evaluating new approaches. Based on this analysis, we provided recommendations for potential future directions in this area.

Comparative in vitro toxicity assessment of perfluorinated carboxylic acids.

Science.gov (United States)

Mahapatra, Cecon T; Damayanti, Nur P; Guffey, Samuel C; Serafin, Jennifer S; Irudayaraj, Joseph; Sepúlveda, Maria S

2017-06-01

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are synthetic fluorinated compounds that are highly bioaccumulative and persistent organic pollutants. Perfluorooctanoic acid (PFOA), an eight-carbon chain perfluorinated carboxylic acid, was used heavily for the production of fluoropolymers, but concerns have led to its replacement by shorter carbon chain homologues such as perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA). However, limited toxicity data exist for these substitutes. We evaluated the toxicity of PFOA, PFHxA and PFBA on a zebrafish liver cell line and investigated the effects of exposure on cell metabolism. Gross toxicity after 96 h of exposure was highest for PFOA and PFO - , while PFHxA and PFBA exhibited lower toxicity. Although the structural similarity of these compounds to fatty acids suggests the possibility of interference with the transport and metabolism of lipids, we could not detect any differential expression of peroxisome proliferator-activated receptor (ppar-α, -β and -γ), fabp3 and crot genes after 96 h exposure to up to 10 ppm of the test compounds. However, we observed localized lipid droplet accumulation only in PFBA-exposed cells. To study the effects of these compounds on cell metabolism, we conducted fluorescence lifetime imaging microscopy using naturally fluorescent biomarkers, NADH and FAD. The fluorescence lifetimes of NADH and FAD and the bound/free ratio of each of these coenzymes decreased in a dose- and carbon length-dependent manner, suggesting disruption of cell metabolism. In sum, our study revealed that PFASs with shorter carbon chains are less toxic than PFOA, and that exposure to sublethal dosage of PFOA, PFHxA or PFBA affects cell metabolism. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

Science.gov (United States)

Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

2013-01-01

The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-07-01

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

IRIS Toxicological Review of Thallium and Compounds ...

Science.gov (United States)

Thallium compounds are used in the semiconductor industry, the manufacture of optic lenses and low-melting glass, low-temperature thermometers, alloys, electronic devices, mercury lamps, fireworks, and imitation germs, and clinically as an imaging agent in the diagnosis of certain tumors. EPA's assessment of noncancer health effects and carcinogenic potential of thallium compounds was last prepared and added to the IRIS database between 1988 and 1990. The IRIS program is preparing an assessment that will incorporate current health effects information available for thallium and compounds, and current risk assessment methods. The IRIS assessment for thallium compounds will consist of a Toxicological Review and IRIS Summary. The Toxicological Review is a critical review of the physiochemical and toxicokinetic properties of a chemical, and its toxicity in humans and experimental systems. The assessment will present reference values for the noncancer effects of thallium compounds (RfD and Rfc), and a cancer assessment. The Toxicological Review and IRIS Summary have been subject to Agency review, Interagency review, and external scientific peer review. The final product will reflect the Agency opinion on the overall toxicity of thallium and compounds. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for thallium and compounds. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effec

Role of P27 -P55 operon from Mycobacterium tuberculosis in the resistance to toxic compounds

Directory of Open Access Journals (Sweden)

Cataldi Angel A

2011-07-01

Full Text Available Abstract Background The P27-P55 (lprG-Rv1410c operon is crucial for the survival of Mycobacterium tuberculosis, the causative agent of human tuberculosis, during infection in mice. P55 encodes an efflux pump that has been shown to provide Mycobacterium smegmatis and Mycobacterium bovis BCG with resistance to several drugs, while P27 encodes a mannosylated glycoprotein previously described as an antigen that modulates the immune response against mycobacteria. The objective of this study was to determine the individual contribution of the proteins encoded in the P27-P55 operon to the resistance to toxic compounds and to the cell wall integrity of M. tuberculosis. Method In order to test the susceptibility of a mutant of M. tuberculosis H37Rv in the P27-P55 operon to malachite green, sodium dodecyl sulfate, ethidium bromide, and first-line antituberculosis drugs, this strain together with the wild type strain and a set of complemented strains were cultivated in the presence and in the absence of these drugs. In addition, the malachite green decolorization rate of each strain was obtained from decolorization curves of malachite green in PBS containing bacterial suspensions. Results The mutant strain decolorized malachite green faster than the wild type strain and was hypersensitive to both malachite green and ethidium bromide, and more susceptible to the first-line antituberculosis drugs: isoniazid and ethambutol. The pump inhibitor reserpine reversed M. tuberculosis resistance to ethidium bromide. These results suggest that P27-P55 functions through an efflux-pump like mechanism. In addition, deletion of the P27-P55 operon made M. tuberculosis susceptible to sodium dodecyl sulfate, suggesting that the lack of both proteins causes alterations in the cell wall permeability of the bacterium. Importantly, both P27 and P55 are required to restore the wild type phenotypes in the mutant. Conclusions The results clearly indicate that P27 and P55 are

Chemistry and technology of boron and its compounds

International Nuclear Information System (INIS)

Zhigach, A.F.; Parfenov, B.P.; Svitsyn, R.A.

1995-01-01

The results of research dealing with development of technologies of boron trichloride, boron hydride, aminoderivative boron hydrides, metal borohydrides, carboranes, carborane-containing polymers, carried out at the institute of organoelemental compounds, are presented. Physicochemical properties of the compounds have been studied and analytical methods have been developed. Data on toxicity and fire hazard of boron compounds are provided

Dioxin and Dioxin-Like Compounds Toxic Equivalency Information

Science.gov (United States)

EPA requires that, in addition to the total grams released for the entire dioxin and dioxin-like compounds category, TRI facilities must report the quantity for each individual member on a new Form R Schedule 1.

The toxicity of plutonium

International Nuclear Information System (INIS)

Ramsden, D.; Johns, T.F.

1977-01-01

Reference is made to recent publications concerned with the radiotoxicity of inhaled insoluble Pu compounds. The publications are a paper by Thorne and Vennart (Nature 263:555 (1976)), a report entitled 'The Toxicity of Plutonium', (London (HMSO), 1975), and the 'Sixth Report of the Royal Commission on Environmental Pollution', (Cmnd. 6618, London (HMSO), 1976). Thorne and Vennart concluded that the previously accepted value for the maximum permissible annual intake (MPAI) of such compounds may be too high by a factor of about five, and a similar conclusion was reached in the other two publications. It is thought by the present authors that the methods which have been used to suggest new values for the MPAI are unduly pessimistic for high-fired PuO 2 ; calculations have been based on the lung model of ICRP Publication 19 'The Metabolism of Compounds of Plutonium and the Other Actinides', (International Commission of Radiological Protection, 1972). This involves concluding that the risks to bone and liver are comparable to those for lung. This is discussed and it is thought that the previously established idea that the lung is the critical organ remains substantially correct for the case of high-fired PuO 2 . (U.K.)

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)

1997-11-10

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.

Lethal and sublethal endpoints observed for Artemia exposed to two reference toxicants and an ecotoxicological concern organic compound.

Science.gov (United States)

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

2016-01-01

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. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of pH on the bioconcentration and toxicity of weak organic electrolytes

DEFF Research Database (Denmark)

Rendal, Cecilie

to the bioconcentration of ionizing organic compounds showed that this fraction cannot safely be overlooked. The work presented in this thesis suggests that the standard test procedures used to test toxicity and bioconcentration are not sufficient to fully illuminate the ecotoxicity of ionizing organic compounds unless......Many of the compounds in use today have ionizing properties. Investigations have shown that around half of the compounds preregistered for REACH and over 70% of all pharmaceuticals are ionizing organic compounds. These compounds may pose a risk when they are released into the environment....... Ionization, however, complicates the environmental risk assessment of these compounds because the uptake processes of the neutral fraction differ from the processes of the ionized fraction. Acids are increasingly neutral at pH levels below the pKa while bases are increasingly neutral at pH levels above the p...

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

Science.gov (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

2016-03-03

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

Reproductive activities of Heliotropium indicum isolate against Helopeltis theivora and toxicity evaluation in mice.

Science.gov (United States)

Dolui, A K; Debnath, Manabendra; De, B; Kumar, Atul

2012-05-01

A new compound E was isolated from the methanolic extract of the leaves of Heliotropium indicum by chromatographic fractionation. In the present study, the effect of the compound E on reproduction of Helopeltis theivora has been evaluated. The acute toxicity study (LD50) and sub-acute toxicity studies (haematological, biochemical and histopathological parameters) in albino Swiss mice were carried out to evaluate the safety aspect of the compound E. The compound showed significant inhibitory effect on the reproductive life of H. theivora. The oviposition period, fecundity and hatching percentage of H. theivora were found to be 15.67 days, 39.33 and 28.00% respectively after treatment with 2% compound E, whereas the control value were found to be 20.33 days, 77.67 and 77.33% respectively. The LD50 of the compound was found to be 780 mg kg(-1) in Swiss albino female mice. The compound did not show any toxicity in mice at sub-lethal dose treatment (78 mg kg(-1) b. wt., once daily) for 21 days as evident from different haematological, biochemical and histopathological parameters in compound E treated group when compared with control.

Toxic effects of two essential oils and their constituents on the mealworm beetle, Tenebrio molitor.

Science.gov (United States)

Martínez, L C; Plata-Rueda, A; Colares, H C; Campos, J M; Dos Santos, M H; Fernandes, F L; Serrão, J E; Zanuncio, J C

2017-12-14

The study identified insecticidal effects from the cinnamon and clove essential oils in Tenebrio molitor L. (Coleoptera: Tenebrionidae). The lethal concentrations (LC50 and LC90), lethal time, and repellent effect on larvae, pupae, and adults of T. molitor after exposure to six concentrations of each essential oil and toxic compounds were evaluated. The chemical composition of the cinnamon oil was also determined and primary compounds were eugenol (10.19%), trans-3-caren-2-ol (9.92%), benzyl benzoate (9.68%), caryophyllene (9.05%), eugenyl acetate (7.47%), α-phellandrene (7.18%), and α-pinene (6.92%). In clove essential oil, the primary compounds were eugenol (26.64%), caryophyllene (23.73%), caryophyllene oxide (17.74%), 2-propenoic acid (11.84%), α-humulene (10.48%), γ-cadinene (4.85%), and humulene oxide (4.69%). Cinnamon and clove essential oils were toxic to T. molitor. In toxic chemical compounds, eugenol have stronger contact toxicity in larvae, pupae, and adult than caryophyllene oxide, followed by α-pinene, α-phellandrene, and α-humulene. In general, the two essential oils were toxic and repellent to adult T. molitor. Cinnamon and clove essential oils and their compounds caused higher mortality and repellency on T. molitor and, therefore, have the potential for integrated management programs of this insect.

Devices for collecting chemical compounds

Science.gov (United States)

Scott, Jill R; Groenewold, Gary S

2013-12-24

A device for sampling chemical compounds from fixed surfaces and related methods are disclosed. The device may include a vacuum source, a chamber and a sorbent material. The device may utilize vacuum extraction to volatilize the chemical compounds from a fixed surface so that they may be sorbed by the sorbent material. The sorbent material may then be analyzed using conventional thermal desorption/gas chromatography/mass spectrometry (TD/GC/MS) instrumentation to determine presence of the chemical compounds. The methods may include detecting release and presence of one or more chemical compounds and determining the efficacy of decontamination. The device may be useful in collection and analysis of a variety of chemical compounds, such as residual chemical warfare agents, chemical attribution signatures and toxic industrial chemicals.

Particle size distribution of aerosols sprayed from household hand-pump sprays containing fluorine-based and silicone-based compounds.

Science.gov (United States)

Kawakami, Tsuyoshi; Isama, Kazuo; Ikarashi, Yoshiaki

2015-01-01

Japan has published safety guideline on waterproof aerosol sprays. Furthermore, the Aerosol Industry Association of Japan has adopted voluntary regulations on waterproof aerosol sprays. Aerosol particles of diameter less than 10 µm are considered as "fine particles". In order to avoid acute lung injury, this size fraction should account for less than 0.6% of the sprayed aerosol particles. In contrast, the particle size distribution of aerosols released by hand-pump sprays containing fluorine-based or silicone-based compounds have not been investigated in Japan. Thus, the present study investigated the aerosol particle size distribution of 16 household hand-pump sprays. In 4 samples, the ratio of fine particles in aerosols exceeded 0.6%. This study confirmed that several hand-pump sprays available in the Japanese market can spray fine particles. Since the hand-pump sprays use water as a solvent and their ingredients may be more hydrophilic than those of aerosol sprays, the concepts related to the safety of aerosol-sprays do not apply to the hand pump sprays. Therefore, it may be required for the hand-pump spray to develop a suitable method for evaluating the toxicity and to establish the safety guideline.

Assessment of an in vitro model of human cells to evaluate the toxic and irritating potential of chemical compounds

Directory of Open Access Journals (Sweden)

M. Catalano

2011-01-01

Full Text Available We attempted to induce differentation in unidifferentiated NCTC2544 human keratinocyte line, by exposure to ZnSO4 and CaCl2. Analysis of specific markers, transglutaminase I, involucrin and loricrin, show that basal NCTC2544 (BL reached spinous- (SL and granular-like (GL phenotypes. BL-, SI- and GL- NCTC were exposed to SDS, as irritant stimulus and Neutral red uptake (NRU and MTT cytoxicity tests evidenced a relatively higher toxicity in SL- and GL cells on lysosomes respect to mitochondria. ILIα cytokine was monitored as early inflammation marker. The complex of data provides evidence for the suitability of our in vitro model to the analysis of cytotoxic/biological effects of topically applied exogenous compounds.

Screening the Emission Sources of Volatile Organic Compounds (VOCs) in China Based on Multi-effect Evaluation

Science.gov (United States)

Niu, H., Jr.

2015-12-01

Volatile organic compounds (VOCs) in the atmosphere have adverse impacts via three main pathways: photochemical ozone formation, secondary organic aerosol production, and direct toxicity to humans. Few studies have integrated these effects to prioritize control measures for VOCs sources. In this study, we developed a multi-effect evaluation methodology based on updated emission inventories and source profiles, which was combined with ozone formation potential (OFP), secondary organic aerosol potential (SOAP), and VOC toxicity data to identify important emission sources and key species. We derived species-specific emission inventories for 152 sources. The OFPs, SOAPs, and toxicity of each source were determined, and the contribution and share of each source to each of these adverse effects was calculated. Weightings were given to the three adverse effects by expert scoring, and the integrated impact was determined. Using 2012 as the base year, solvent usage and industrial process were found to be the most important anthropogenic sources, accounting for 24.2 and 23.1% of the integrated environmental effect, respectively. This was followed by biomass burning, transportation, and fossil fuel combustion, all of which had a similar contribution ranging from 16.7 to 18.6%. The top five industrial sources, including plastic products, rubber products, chemical fiber products, the chemical industry, and oil refining, accounted for nearly 70.0% of industrial emissions. In China, emissions reductions are required for styrene, toluene, ethylene, benzene, and m/p-xylene. The 10 most abundant chemical species contributed 76.5% of the integrated impact. Beijing, Chongqing, Shanghai, Jiangsu, and Guangdong were the five leading provinces when considering the integrated effects. Besides, the chemical mass balance model (CMB) was used to verify the VOCs inventories of 47 cities in China, so as to optimize our evaluation results. We suggest that multi-effect evaluation is necessary to

Seasonal variability in irradiance affects herbicide toxicity to the marine flagellate Dunaliella tertiolecta

Directory of Open Access Journals (Sweden)

Sascha eSjollema

2014-06-01

Full Text Available Photosynthetically Active Radiation (PAR and Ultraviolet Radiation (UVR of the solar spectrum affect microalgae directly and modify the toxicity of phytotoxic compounds present in water. As a consequence seasonal variable PAR and UVR levels are likely to modulate the toxic pressure of contaminants in the field. Therefore the present study aimed to determine the toxicity of two model contaminants, the herbicides diuron and Irgarol®1051, under simulated irradiance conditions mimicking different seasons. Irradiance conditions of spring and autumn were simulated with a set of Light Emitting Diodes (LEDs. Toxicity of both herbicides was measured individually and in a mixture by determining the inhibition of photosystem II efficiency (ΦPSII of the marine flagellate Dunaliella teriolecta using Pulse Amplitude Modulation (PAM fluorometry. Toxicity of the single herbicides was higher under simulated spring irradiance than under autumn irradiance and this effect was also observed for mixtures of the herbicides. This irradiance dependent toxicity indicates that herbicide toxicity in the field is seasonally variable. Consequently toxicity tests under standard light conditions may overestimate or underestimate the toxic effect of phytotoxic compounds.

Analysis of a ToxCast™ HTS Toxicity Signature for putative Vascular Disruptor Compounds

Science.gov (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...

Identification of compounds with anti-proliferative activity against Trypanosoma brucei brucei strain 427 by a whole cell viability based HTS campaign.

Directory of Open Access Journals (Sweden)

Melissa L Sykes

Full Text Available Human African Trypanosomiasis (HAT is caused by two trypanosome sub-species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Drugs available for the treatment of HAT have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. Hence, there is considerable need to find new alternative and less toxic drugs. An approach to identify starting points for new drug candidates is high throughput screening (HTS of large compound library collections. We describe the application of an Alamar Blue based, 384-well HTS assay to screen a library of 87,296 compounds against the related trypanosome subspecies, Trypanosoma brucei brucei bloodstream form lister 427. Primary hits identified against T.b. brucei were retested and the IC(50 value compounds were estimated for T.b. brucei and a mammalian cell line HEK293, to determine a selectivity index for each compound. The screening campaign identified 205 compounds with greater than 10 times selectivity against T.b. brucei. Cluster analysis of these compounds, taking into account chemical and structural properties required for drug-like compounds, afforded a panel of eight compounds for further biological analysis. These compounds had IC(50 values ranging from 0.22 µM to 4 µM with associated selectivity indices ranging from 19 to greater than 345. Further testing against T.b. rhodesiense led to the selection of 6 compounds from 5 new chemical classes with activity against the causative species of HAT, which can be considered potential candidates for HAT early drug discovery. Structure activity relationship (SAR mining revealed components of those hit compound structures that may be important for biological activity. Four of these compounds have undergone further testing to 1 determine whether they are cidal or static in vitro at the minimum inhibitory concentration (MIC, and 2 estimate the time to kill.

Chloric organic compound

International Nuclear Information System (INIS)

Moalem, F.

2000-01-01

Since many years ago, hazardous and toxic refuses which are results of human activities has been carelessly without any Biological and Engineering facts and knowledge discharged into our land and water. The effects of discharging those materials in environment are different. Some of refuse materials shows short and other has long-time adverse effects in our environment, Among hazardous organic chemical materials, chlorine, consider, to be the main element. Organic materials with chlorine is called chlorine hydrocarbon as a hazardous compound. This paper discuss the hazardous materials especially chloric organic compound and their misuse effects in environment and human being

Microbial degradation of furanic compounds : Biochemistry, genetics, and impact

NARCIS (Netherlands)

Wierckx, N.; Koopman, F.; Ruijssenaars, H.J.; De Winde, J.H.

2011-01-01

Microbial metabolism of furanic compounds, especially furfural and 5-hydroxymethylfurfural (HMF), is rapidly gaining interest in the scientific community. This interest can largely be attributed to the occurrence of toxic furanic aldehydes in lignocellulosic hydrolysates. However, these compounds

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)

2008-07-01

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)

Structure-Based Virtual Screening of Commercially Available Compound Libraries.

Science.gov (United States)

Kireev, Dmitri

2016-01-01

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).

Toxicity assessment strategies, data requirements, and risk assessment approaches to derive health based guidance values for non-relevant metabolites of plant protection products.

Science.gov (United States)

Dekant, Wolfgang; Melching-Kollmuss, Stephanie; Kalberlah, Fritz

2010-03-01

In Europe, limits for tolerable concentrations of "non-relevant metabolites" for active ingredients (AI) of plant protection products in drinking water between 0.1 and 10 microg/L are discussed depending on the toxicological information available. "Non-relevant metabolites" are degradation products of AIs, which do not or only partially retain the targeted toxicities of AIs. For "non-relevant metabolites" without genotoxicity (to be confirmed by testing in vitro), the application of the concept of "thresholds of toxicological concern" results in a health-based drinking water limit of 4.5 microg/L even for Cramer class III compounds, using the TTC threshold of 90 microg/person/day (divided by 10 and 2). Taking into account the thresholds derived from two reproduction toxicity data bases a drinking water limit of 3.0 microg/L is proposed. Therefore, for "non-relevant metabolites" whose drinking water concentration is below 3.0 microg/L, no toxicity testing is necessary. This work develops a toxicity assessment strategy as a basis to delineate health-based limits for "non-relevant metabolites" in ground and drinking water. Toxicological testing is recommended to investigate, whether the metabolites are relevant or not, based on the hazard properties of the parent AIs, as outlined in the SANCO Guidance document. Also, genotoxicity testing of the water metabolites is clearly recommended. In this publication, tiered testing strategies are proposed for non-relevant metabolites, when drinking water concentrations >3.0 microg/L will occur. Conclusions based on structure-activity relationships and the detailed toxicity database on the parent AI should be included. When testing in animals is required for risk assessment, key aspects are studies along OECD-testing guidelines with "enhanced" study designs addressing additional endpoints such as reproductive toxicity and a developmental screening test to derive health-based tolerable drinking water limits with a limited number

Hazard identification of contaminated sites. Ranking potential toxicity of organic sediment extracts in crustacean and fish

Energy Technology Data Exchange (ETDEWEB)

Karlsson, J.; Sundberg, H.; Aakerman, G.; Grunder, K.; Eklund, B.; Breitholtz, M. [Dept. of Applied Environmental Science (ITM), Stockholm Univ. (Sweden)

2008-09-15

Background, aim, and scope: It is well known that contaminated sediments represent a potential long-term source of pollutants to the aquatic environment. To protect human and ecosystem health, it is becoming common to remediate contaminated sites. However, the great cost associated with, e.g., dredging in combination with the large numbers of contaminated sites makes it crucial to pinpoint those sites that are in greatest need of remediation. In most European countries, this prioritization process has almost exclusively been based on chemical analyses of known substances; only seldom toxicity data has been considered. The main objective of the current study was therefore to develop a tool for hazard identification of sediment by ranking potential toxicity of organic sediment extracts in a crustacean and a fish. A secondary objective was to investigate the difference in potential toxicity between compounds with different polarities. Materials and methods Early life stages of the crustacean Nitocra spinipes and the fish Oncorhynchus mykiss, which represent organisms from different trophic levels (primary and secondary consumer) and with different routes of exposure (i.e. ingestion through food, diffusive uptake, and maternal transfer), were exposed to hexane and acetone fractions (semi-polar compounds) of sediment from five locations, ranging from heavily to low contaminated. Preliminary tests showed that the extracts were non-bioavailable to the crustacean when exposed via water, and the extracts were therefore loaded on silica gel. Rainbow trout embryos were exposed using nano-injection technique. Results and discussion Clear concentration-response relationships of both mortality and larval development were observed in all tests with N. spinipes. Also for rainbow trout, the observed effects (e.g., abnormality, hemorrhage, asymmetric yolk sac) followed a dose-related pattern. Interestingly, our results indicate that some of the locations contained toxic semi

Mini-review: Molecular mechanisms of antifouling compounds

KAUST Repository

Qian, Pei-Yuan

2013-04-01

Various antifouling (AF) coatings have been developed to protect submerged surfaces by deterring the settlement of the colonizing stages of fouling organisms. A review of the literature shows that effective AF compounds with specific targets are ones often considered non-toxic. Such compounds act variously on ion channels, quorum sensing systems, neurotransmitters, production/release of adhesive, and specific enzymes that regulate energy production or primary metabolism. In contrast, AF compounds with general targets may or may not act through toxic mechanisms. These compounds affect a variety of biological activities including algal photosynthesis, energy production, stress responses, genotoxic damage, immunosuppressed protein expression, oxidation, neurotransmission, surface chemistry, the formation of biofilms, and adhesive production/release. Among all the targets, adhesive production/release is the most common, possibly due to a more extensive research effort in this area. Overall, the specific molecular targets and the molecular mechanisms of most AF compounds have not been identified. Thus, the information available is insufficient to draw firm conclusions about the types of molecular targets to be used as sensitive biomarkers for future design and screening of compounds with AF potential. In this review, the relevant advantages and disadvantages of the molecular tools available for studying the molecular targets of AF compounds are highlighted briefly and the molecular mechanisms of the AF compounds, which are largely a source of speculation in the literature, are discussed. © 2013 Copyright Taylor and Francis Group, LLC.

Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

International Nuclear Information System (INIS)

Porter, J.B.; Morgan, J.; Hoyes, K.P.; Burke, L.C.; Huehns, E.R.; Hider, R.C.

1990-01-01

The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02)

Rapid screening of aquatic toxicity of several metal-based nanoparticles using the MetPLATE™ bioassay

International Nuclear Information System (INIS)

Pokhrel, Lok R.; Silva, Thilini; Dubey, Brajesh; El Badawy, Amro M.; Tolaymat, Thabet M.; Scheuerman, Phillip R.

2012-01-01

Current understanding of potential toxicity of engineered nanomaterials to aquatic microorganisms is limited for risk assessment and management. Here we evaluate if the MetPLATE™ test can be used as an effective and rapid screening tool to test for potential aquatic toxicity of various metal-based nanoparticles (NPs). The MetPLATE bioassay is a heavy metal sensitive test based on β-galactosidase activity in Escherichia coli. Five different types of metal-based NPs were screened for toxicity: (1) citrate coated nAg (Citrate-nanosilver), (2) polyvinylpyrrolidone coated nAg (PVP-nAg), (3) uncoated nZnO, (4) uncoated nTiO 2 and (5) 1-Octadecylamine coated CdSe Quantum Dots (CdSe QDs); and compared with their corresponding ionic salt toxicity. Citrate-nAg was further fractionated into clean Citrate-nAg, unclean Citrate-nAg and permeate using a tangential flow filtration (TFF) system to eliminate residual ions and impurities from the stock Citrate-nAg suspension and also to differentiate between ionic- versus nano-specific toxicity. Our results showed that nAg, nZnO and CdSe QDs were less toxic than their corresponding ionic salts tested, while nano- or ionic form of TiO 2 was not toxic as high as 2.5 g L −1 to the MetPLATE™ bacteria. Although coating-dependent toxicity was noticeable between two types of Ag NPs evaluated, particle size and surface charge were not adequate to explain the observed toxicity; hence, the toxicity appeared to be material-specific. Overall, the toxicity followed the trend: CdCl 2 > AgNO 3 > PVP-nAg > unclean Citrate-nAg > clean Citrate-nAg > ZnSO 4 > nZnO > CdSe QDs > nTiO 2 /TiO 2 . These results indicate that an evaluation of β-galactosidase inhibition in MetPLATE™ E. coli can be an important consideration for rapid screening of metal-based NP toxicity, and should facilitate ecological risk assessment of these emerging contaminants. - Highlights: ► MetPLATE bioassay was evaluated as a rapid screening tool for nanotoxicity. �

Rapid toxicity assessment using an in vivo enzyme test for Brachionus plicatilis (Rotifera).

Science.gov (United States)

Moffat, B D; Snell, T W

1995-02-01

A 1-hr in vivo enzyme inhibition assay based on esterase activity has good potential for marine toxicity assessment. A test was developed for the rotifer Brachionus plicatilis based on the nonfluorescent substrate fluorescein diacetate (FDA), which is metabolized by esterases to a fluorescent product. Enzyme inhibition, as determined by reduced fluorescence, can be scored visually or quantified using a fluorometer. Quantification of fluorescence permits the calculation of NOEC, LOEC, chronic value, and IC20. The 1-hr esterase inhibition test has sensitivity comparable to that of 24-hr rotifer acute tests for several compounds. The toxicity of six compounds was examined using the quantified assay. The resulting IC20s were within a factor of 3 of the 24-hour LC50s. IC20 values ranged from 0.017 mg/l for tributyltin to 3.1 mg/l for zinc, with an average coefficient of variation of 17.8%. Electrophoretic analysis of rotifer homogenates suggested that a single C esterase (acetylesterase) was responsible for FDA metabolism in B. plicatilis. Several other aquatic species are capable of metabolizing FDA, including Brachionus calyciflorus, Mysidopsis bahia, Menidia beryllina, Pimephales promelas, Ceriodaphnia dubia, Daphnia pulex, Artemia salina, and Ophryotrocha sp. The esterase inhibition test is an attractive tool for assessing aquatic toxicity because of its speed, simplicity, sensitivity, and applicability to a broad range of aquatic species.

Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

Directory of Open Access Journals (Sweden)

Marsel R. Garipov

2017-01-01

Full Text Available Two novel quaternary ammonium salts, bis-triazolium derivatives of fluconazole and pyridoxine, were synthesized by reaction of fluconazole with pyridoxine-based synthetic intermediates. The leading compound demonstrated pronounced antimycotic and antibacterial in vitro activity, comparable to or exceeding that of the reference antifungal (fluconazole, terbinafine and antibacterial/antiseptic (miramistin, benzalkonium chloride agents. In contrast to many antimicrobials, the leading compound was also active against biofilm-embedded staphylococci and Escherichia coli. While no biofilm structure destruction occurred, all compounds were able to diffuse into the matrix and reduce the number of colony-forming units by three orders of magnitude at 16 × MBC. The leading compound was significantly less toxic than miramistin and benzalkonium chloride and more toxic than the reference antifungal drugs. The obtained results make the described chemotype a promising starting point for the development of new broad-spectrum antimicrobial therapies with powerful effect on fungal and bacterial pathogens including their biofilm-embedded forms.

Toxicity of the sulfhydryl-containing radioprotector dithiothreitol

International Nuclear Information System (INIS)

Held, K.D.; Biaglow, J.E.

1987-01-01

The toxicity of the sulfhydryl-containing radioprotector dithiothreitol (DTT) has been studied in Chinese hamster V79 cells growing in monolayer. Under the conditions used here DTT causes a biphasic toxic response in which low concentrations of the drug (0.5 to 1.0 mM) are more toxic than are lower (0.2 mM) or higher (10 mM) concentrations. This response is similar to that seen by others with other sulfhydryl compounds. This DTT-induced toxicity is prevented by catalase, glutathione, and lowered temperatures. The toxicity is enhanced by some metal chelators (EDTA) but prevented by others (desferal). Metals (copper and iron) can either enhance or decrease the toxicity depending on their concentration and whether the exposure is in medium or in buffered salt solution. The results suggest a complex chain of chemical reactions and interactions with a role of H/sub 2/O/sub 2/ and perhaps . OH in this DTT toxicity. This is discussed

Lectin-based food poisoning: a new mechanism of protein toxicity.

Science.gov (United States)

Miyake, Katsuya; Tanaka, Toru; McNeil, Paul L

2007-08-01

Ingestion of the lectins present in certain improperly cooked vegetables can result in acute GI tract distress, but the mechanism of toxicity is unknown. In vivo, gut epithelial cells are constantly exposed to mechanical and other stresses and consequently individual cells frequently experience plasma membrane disruptions. Repair of these cell surface disruptions allows the wounded cell to survive: failure results in necrotic cell death. Plasma membrane repair is mediated, in part, by an exocytotic event that adds a patch of internal membrane to the defect site. Lectins are known to inhibit exocytosis. We therefore tested the novel hypothesis that lectin toxicity is due to an inhibitory effect on plasma membrane repair. Repair of plasma membrane disruptions and exocytosis of mucus was assessed after treatment of cultured cell models and excised segments of the GI tract with lectins. Plasma membrane disruptions were produced by focal irradiation of individual cells, using a microscope-based laser, or by mechanical abrasion of multiple cells, using a syringe needle. Repair was then assessed by monitoring the cytosolic penetration of dyes incapable of crossing the intact plasma membrane. We found that cell surface-bound lectins potently inhibited plasma membrane repair, and the exocytosis of mucus that normally accompanies the repair response. Lectins potently inhibit plasma membrane repair, and hence are toxic to wounded cells. This represents a novel form of protein-based toxicity, one that, we propose, is the basis of plant lectin food poisoning.

Lectin-based food poisoning: a new mechanism of protein toxicity.

Directory of Open Access Journals (Sweden)

Katsuya Miyake

Full Text Available BACKGROUND: Ingestion of the lectins present in certain improperly cooked vegetables can result in acute GI tract distress, but the mechanism of toxicity is unknown. In vivo, gut epithelial cells are constantly exposed to mechanical and other stresses and consequently individual cells frequently experience plasma membrane disruptions. Repair of these cell surface disruptions allows the wounded cell to survive: failure results in necrotic cell death. Plasma membrane repair is mediated, in part, by an exocytotic event that adds a patch of internal membrane to the defect site. Lectins are known to inhibit exocytosis. We therefore tested the novel hypothesis that lectin toxicity is due to an inhibitory effect on plasma membrane repair. METHODS AND FINDINGS: Repair of plasma membrane disruptions and exocytosis of mucus was assessed after treatment of cultured cell models and excised segments of the GI tract with lectins. Plasma membrane disruptions were produced by focal irradiation of individual cells, using a microscope-based laser, or by mechanical abrasion of multiple cells, using a syringe needle. Repair was then assessed by monitoring the cytosolic penetration of dyes incapable of crossing the intact plasma membrane. We found that cell surface-bound lectins potently inhibited plasma membrane repair, and the exocytosis of mucus that normally accompanies the repair response. CONCLUSIONS: Lectins potently inhibit plasma membrane repair, and hence are toxic to wounded cells. This represents a novel form of protein-based toxicity, one that, we propose, is the basis of plant lectin food poisoning.

Combinatorial QSAR modeling of chemical toxicants tested against Tetrahymena pyriformis.

Science.gov (United States)

Zhu, Hao; Tropsha, Alexander; Fourches, Denis; Varnek, Alexandre; Papa, Ester; Gramatica, Paola; Oberg, Tomas; Dao, Phuong; Cherkasov, Artem; Tetko, Igor V

2008-04-01

Selecting most rigorous quantitative structure-activity relationship (QSAR) approaches is of great importance in the development of robust and predictive models of chemical toxicity. To address this issue in a systematic way, we have formed an international virtual collaboratory consisting of six independent groups with shared interests in computational chemical toxicology. We have compiled an aqueous toxicity data set containing 983 unique compounds tested in the same laboratory over a decade against Tetrahymena pyriformis. A modeling set including 644 compounds was selected randomly from the original set and distributed to all groups that used their own QSAR tools for model development. The remaining 339 compounds in the original set (external set I) as well as 110 additional compounds (external set II) published recently by the same laboratory (after this computational study was already in progress) were used as two independent validation sets to assess the external predictive power of individual models. In total, our virtual collaboratory has developed 15 different types of QSAR models of aquatic toxicity for the training set. The internal prediction accuracy for the modeling set ranged from 0.76 to 0.93 as measured by the leave-one-out cross-validation correlation coefficient ( Q abs2). The prediction accuracy for the external validation sets I and II ranged from 0.71 to 0.85 (linear regression coefficient R absI2) and from 0.38 to 0.83 (linear regression coefficient R absII2), respectively. The use of an applicability domain threshold implemented in most models generally improved the external prediction accuracy but at the same time led to a decrease in chemical space coverage. Finally, several consensus models were developed by averaging the predicted aquatic toxicity for every compound using all 15 models, with or without taking into account their respective applicability domains. We find that consensus models afford higher prediction accuracy for the

Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

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Feng, Guo; Chen, Yun-Long; Li, Wei; Li, Lai-Lai; Wu, Zeng-Guang; Wu, Zi-Jun; Hai, Yue; Zhang, Si-Chao; Zheng, Chuan-Qi; Liu, Chang-Xiao; He, Xin

2018-06-01

Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. A Q-marker database of processed RWI by "sweat soaking method" was established according to the results

Bioprocesses for the Removal of Volatile Sulfur Compounds from Gas Streams

NARCIS (Netherlands)

Janssen, A.J.H.; bosch, van den P.L.M.; Leerdam, van R.C.; Graaff, de C.M.

2013-01-01

This chapter describes the biological removal of sulphur compounds from gas streams. First, an overview is given of the toxicity of sulphur compounds to animals and humans whereafter biological and industrial formation routes for (organic) sulphur compounds are given. Microbial degradation routes of

Thin sensing layer based on semi-conducting β-cyclodextrin rotaxane for toxic metals detection

Energy Technology Data Exchange (ETDEWEB)

Teka, S.; Gaied, A.; Jaballah, N. [Laboratoire des Interfaces et Matériaux Avancés (LIMA), Université de Monastir, Faculté des Sciences de Monastir, Bd. de l' Environnement, 5019 Monastir (Tunisia); Xiaonan, S. [Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baı̈ f, 75205 Paris Cedex 13 (France); Majdoub, M., E-mail: mustapha.majdoub@fsm.rnu.tn [Laboratoire des Interfaces et Matériaux Avancés (LIMA), Université de Monastir, Faculté des Sciences de Monastir, Bd. de l' Environnement, 5019 Monastir (Tunisia)

2016-02-15

Highlights: • Microwave-assisted synthesis of rotaxane based on anthracene and β-cyclodextrin. • Morphological and optical characterization of thin solid film. • Elaboration of impedimetric gold/rotaxane sensor. • Investigation of the membrane sensitivity towards Hg{sup 2+}, Cu{sup 2+} and Pb{sup 2+} cations. - Abstract: An impedimetric sensor based on a new semi-conducting rotaxane has been described for detection of toxic cations. The rotaxane, consists on a π-conjugated material encapsulated into β-cyclodextrin (β-CD); it has been synthesized via the Williamson reaction under microwaves irradiation. The supramolecular structure of the compound was confirmed by NMR and FT-IR spectroscopies. A thin solid film of the rotaxane was deposited by spin-coating to develop a new electrochemical sensor. The morphological properties of the organic membrane were evaluated using contact angle measurements and atomic force microscopy. The gold/rotaxane/solution interfaces were investigated by electrochemical impedance spectroscopy and the obtained data were fitted using an equivalent electrical circuit. The response of the gold/rotaxane membrane towards Hg{sup 2+}, Cu{sup 2+} and Pb{sup 2+} cations was studied and the results showed a good sensitivity to the mercury cations.

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

Energy Technology Data Exchange (ETDEWEB)

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

2007-07-01

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

Transformation of toxic potential of Jatropha curcas (Ratanjyot into protein source: A mini-review

Directory of Open Access Journals (Sweden)

Amit Shukla

2015-06-01

Full Text Available The production of animal largely depends on supplying of quality feed and proteinaceous supplement to the animals. Jatropha plant can grow in the barren lands, and are used as a source of biodiesel. Besides, the plant may act as a rich proteinaceous source. However, the antinutritional factors present in the seed and seed oil of the plant may hamper the availability and beneficial use of the plant. Curcin and phorbol esters are the major toxic compounds present in the plant; these toxic compounds cause to produce liver and kidney diseases. Detoxification of these toxic compounds by physical and chemical means converting to less toxic seed cake may serve the purpose of using this plant in future as a replacement of costly protein supplement for animals. Therefore, in modern world, it is recommended to utilize the protein source by neutralizing the antinutritional factors. This mini-review describes the updates on how J. curcas can be utilized as a supplementary source of protein for animals by decreasing its toxicity.

Modeling Aquatic Toxicity through Chromatographic Systems.

Science.gov (United States)

Fernández-Pumarega, Alejandro; Amézqueta, Susana; Farré, Sandra; Muñoz-Pascual, Laura; Abraham, Michael H; Fuguet, Elisabet; Rosés, Martí

2017-08-01

Environmental risk assessment requires information about the toxicity of the growing number of chemical products coming from different origins that can contaminate water and become toxicants to aquatic species or other living beings via the trophic chain. Direct toxicity measurements using sensitive aquatic species can be carried out but they may become expensive and ethically questionable. Literature refers to the use of chromatographic measurements that correlate to the toxic effect of a compound over a specific aquatic species as an alternative to get toxicity information. In this work, we have studied the similarity in the response of the toxicity to different species and we have selected eight representative aquatic species (including tadpoles, fish, water fleas, protozoan, and bacteria) with known nonspecific toxicity to chemical substances. Next, we have selected four chromatographic systems offering good perspectives for surrogation of the eight selected aquatic systems, and thus prediction of toxicity from the chromatographic measurement. Then toxicity has been correlated to the chromatographic retention factor. Satisfactory correlation results have been obtained to emulate toxicity in five of the selected aquatic species through some of the chromatographic systems. Other aquatic species with similar characteristics to these five representative ones could also be emulated by using the same chromatographic systems. The final aim of this study is to model chemical products toxicity to aquatic species by means of chromatographic systems to reduce in vivo testing.

Assessment of chloroethene degradation rates based on ratios of daughter/parent compounds in groundwater plumes

Science.gov (United States)

Höhener, Patrick

2014-05-01

Chlorinated solvent spills at industrial and urban sites create groundwater plumes where tetrachloro- and trichloroethene may degrade to their daughter compounds, dichloroethenes, vinyl chloride and ethane. The assessment of degradation and natural attenuation at such sites may be based on the analysis and inverse modelling of concentration data, on the calculation of mass fluxes in transsects, and/or on the analysis of stable isotope ratios in the ethenes. Relatively few work has investigated the possibility of using ratio of concentrations for gaining information on degradation rates. The use of ratios bears the advantage that dilution of a single sample with contaminant-free water does not matter. It will be shown that molar ratios of daughter to parent compounds measured along a plume streamline are a rapid and robust mean of determining whether degradation rates increase or decrease along the degradation chain, and allow furthermore a quantitation of the relative magnitude of degradation rates compared to the rate of the parent compound. Furthermore, ratios of concentration will become constant in zones where degradation is absent, and this allows to sketching the extension of actively degrading zones. The assessment is possible for pure sources and also for mixed sources. A quantification method is proposed in order to estimate first-order degradation rates in zones of constant degradation activity. This quantification method includes corrections that are needed due to longitudinal and transversal dispersivity. The method was tested on a number of real field sites from literature. At the majority of these sites, the first-order degradation rates were decreasing along the degradation chain from tetrachloroethene to vinyl chloride, meaning that the latter was often reaching important concentrations. This is bad news for site owners due to the increased toxicity of vinyl chloride compared to its parent compounds.

Toxicity and efficacy of carbon nanotubes and graphene: the utility of carbon-based nanoparticles in nanomedicine.

Science.gov (United States)

Zhang, Yongbin; Petibone, Dayton; Xu, Yang; Mahmood, Meena; Karmakar, Alokita; Casciano, Dan; Ali, Syed; Biris, Alexandru S

2014-05-01

Carbon-based nanomaterials have attracted great interest in biomedical applications such as advanced imaging, tissue regeneration, and drug or gene delivery. The toxicity of the carbon nanotubes and graphene remains a debated issue although many toxicological studies have been reported in the scientific community. In this review, we summarize the biological effects of carbon nanotubes and graphene in terms of in vitro and in vivo toxicity, genotoxicity and toxicokinetics. The dose, shape, surface chemistry, exposure route and purity play important roles in the metabolism of carbon-based nanomaterials resulting in differential toxicity. Careful examination of the physico-chemical properties of carbon-based nanomaterials is considered a basic approach to correlate the toxicological response with the unique properties of the carbon nanomaterials. The reactive oxygen species-mediated toxic mechanism of carbon nanotubes has been extensively discussed and strategies, such as surface modification, have been proposed to reduce the toxicity of these materials. Carbon-based nanomaterials used in photothermal therapy, drug delivery and tissue regeneration are also discussed in this review. The toxicokinetics, toxicity and efficacy of carbon-based nanotubes and graphene still need to be investigated further to pave a way for biomedical applications and a better understanding of their potential applications to humans.

Neurotoxicity of fragrance compounds: A review.

Science.gov (United States)

Pinkas, Adi; Gonçalves, Cinara Ludvig; Aschner, Michael

2017-10-01

Fragrance compounds are chemicals belonging to one of several families, which are used frequently and globally in cosmetics, household products, foods and beverages. A complete list of such compounds is rarely found on the ingredients-list of such products, as "fragrance mixtures" are defined as "trade secrets" and thus protected by law. While some information regarding the general toxicity of some of these compounds is available, their neurotoxicity is known to a lesser extent. Here, we discuss the prevalence and neurotoxicity of fragrance compounds belonging to the three most common groups: phthalates, synthetic musks and chemical sensitizers. Copyright © 2017 Elsevier Inc. All rights reserved.

A Non-lethal water-based removal-reapplication technique for behavioral analysis of cuticular compounds of ants.

Science.gov (United States)

Roux, Olivier; Martin, Jean-Michel; Ghomsi, Nathan Tene; Dejean, Alain

2009-08-01

Interspecific relationships among insects are often mediated by chemical cues, including non-volatile cuticular compounds. Most of these compounds are hydrocarbons that necessitate the use of solvents for their extraction, identification, and manipulation during behavioral assays. The toxicity of these solvents often precludes the removal and reapplication of hydrocarbons from and to live insects. As a consequence, dummies often are used in behavioral assays, but their passivity can bias the behavior of the responding insects. To overcome these limitations, we propose a method where cuticular compounds are extracted from live ants by placing them into glass vials half-filled with tepid water (ca. 34 degrees C) and vigorously shaking the vials to form an emulsion whose supernatant can be analyzed and/or reapplied to other ants. We demonstrate that cuticular compounds can be extracted from workers of the red fire ant, Solenopsis saevissima, and reapplied to the cuticle of workers from a sympatric species, Camponotus blandus (both Hymenoptera: Formicidae), while keeping the ants alive. Gas chromatographic-mass spectrometric analysis and behavioral assays were used to confirm the successful transfer of the behaviorally active compounds.

Recreating the seawater mixture composition of HOCs in toxicity tests with Artemia franciscana by passive dosing

Energy Technology Data Exchange (ETDEWEB)

Rojo-Nieto, E., E-mail: elisa.rojo@uca.es [Andalusian Centre of Marine Science and Technology (CACYTMAR), Department of Environmental Technologies, University of Cadiz, 11510 Puerto Real (Spain); Smith, K.E.C. [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark); Perales, J.A. [Andalusian Centre of Marine Science and Technology (CACYTMAR), Department of Environmental Technologies, University of Cadiz, 11510 Puerto Real (Spain); Mayer, P. [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark)

2012-09-15

The toxicity testing of hydrophobic organic compounds (HOCs) in aquatic media is generally challenging, and this is even more problematic for mixtures. The hydrophobic properties of these compounds make them difficult to dissolve, and subsequently to maintain constant exposure concentrations. Evaporative and sorptive losses are highly compound-specific, which can alter not only total concentrations, but also the proportions between the compounds in the mixture. Therefore, the general aim of this study was to explore the potential of passive dosing for testing the toxicity of a PAH mixture that recreates the mixture composition found in seawater from a coastal area of Spain, the Bay of Algeciras. First, solvent spiking and passive dosing were compared for their suitability to determine the acute toxicity to Artemia franciscana nauplii of several PAHs at their respective solubility limits. Second, passive dosing was applied to recreate the seawater mixture composition of PAHs measured in a Spanish monitoring program, to test the toxicity of this mixture at different levels. HPLC analysis was used to confirm the reproducibility of the dissolved exposure concentrations for the individual PAHs and mixtures. This study shows that passive dosing has some important benefits in comparison with solvent spiking for testing HOCs in aquatic media. These include maintaining constant exposure concentrations, leading to higher reproducibility and a relative increase in toxicity. Passive dosing is also able to faithfully reproduce real mixtures of HOCs such as PAHs, in toxicity tests, reproducing both the levels and proportions of the different compounds. This provides a useful approach for studying the toxicity of environmental mixtures of HOCs, both with a view to investigating their toxicity but also for determining safety factors before such mixtures result in detrimental effects.

Toxicity of some formation fluids and methods of rehabilitation subsequent to their spillage

Energy Technology Data Exchange (ETDEWEB)

Shaw, D R

1976-01-01

This paper deals with the effects that formation fluids have on animal and plant life. Crude oil is a mixture--not only of hydrocarbons, but of suspended salts and of sulfur compounds. The toxicity of some of the hydrocarbons and some of the sulfur compounds is discussed, as is the toxicity of salt. Consideration is also given to the complexity of the hydrocarbon components and the influence of refining methods on toxicity. Some mechanisms by which an animal system may attempt to overcome injurious effects are outlined. Finally, methods of aiding recovery are suggested. 26 references.

A portable cell-based impedance sensor for toxicity testing of drinking water.

Science.gov (United States)

Curtis, Theresa M; Widder, Mark W; Brennan, Linda M; Schwager, Steven J; van der Schalie, William H; Fey, Julien; Salazar, Noe

2009-08-07

A major limitation to using mammalian cell-based biosensors for field testing of drinking water samples is the difficulty of maintaining cell viability and sterility without an on-site cell culture facility. This paper describes a portable automated bench-top mammalian cell-based toxicity sensor that incorporates enclosed fluidic biochips containing endothelial cells monitored by Electric Cell-substrate Impedance Sensing (ECIS) technology. Long-term maintenance of cells on the biochips is made possible by using a compact, self-contained disposable media delivery system. The toxicity sensor monitors changes in impedance of cell monolayers on the biochips after the introduction of water samples. The fluidic biochip includes an ECIS electronic layer and a polycarbonate channel layer, which together reduce initial impedance disturbances seen in commercially available open well ECIS chips caused by the mechanics of pipetting while maintaining the ability of the cells to respond to toxicants. A curve discrimination program was developed that compares impedance values over time between the control and treatment channels on the fluidic biochip and determines if they are significantly different. Toxicant responses of bovine pulmonary artery endothelial cells grown on fluidic biochips are similar to cells on commercially-available open well chips, and these cells can be maintained in the toxicity sensor device for at least nine days using an automated media delivery system. Longer-term cell storage is possible; bovine lung microvessel endothelial cells survive for up to four months on the fluidic biochips and remain responsive to a model toxicant. This is the first demonstration of a portable bench top system capable of both supporting cell health over extended periods of time and obtaining impedance measurements from endothelial cell monolayers after toxicant exposure.

Environmentally Friendly Procedure Based on Supercritical Fluid Chromatography and Tandem Mass Spectrometry Molecular Networking for the Discovery of Potent Antiviral Compounds from Euphorbia semiperfoliata.

Science.gov (United States)

Nothias, Louis-Félix; Boutet-Mercey, Stéphanie; Cachet, Xavier; De La Torre, Erick; Laboureur, Laurent; Gallard, Jean-François; Retailleau, Pascal; Brunelle, Alain; Dorrestein, Pieter C; Costa, Jean; Bedoya, Luis M; Roussi, Fanny; Leyssen, Pieter; Alcami, José; Paolini, Julien; Litaudon, Marc; Touboul, David

2017-10-27

A supercritical fluid chromatography-based targeted purification procedure using tandem mass spectrometry and molecular networking was developed to analyze, annotate, and isolate secondary metabolites from complex plant extract mixture. This approach was applied for the targeted isolation of new antiviral diterpene esters from Euphorbia semiperfoliata whole plant extract. The analysis of bioactive fractions revealed that unknown diterpene esters, including jatrophane esters and phorbol esters, were present in the samples. The purification procedure using semipreparative supercritical fluid chromatography led to the isolation and identification of two new jatrophane esters (13 and 14) and one known (15) and three new 4-deoxyphorbol esters (16-18). The structure and absolute configuration of compound 16 were confirmed by X-ray crystallography. This compound was found to display antiviral activity against Chikungunya virus (EC 50 = 0.45 μM), while compound 15 proved to be a potent and selective inhibitor of HIV-1 replication in a recombinant virus assay (EC 50 = 13 nM). This study showed that a supercritical fluid chromatography-based protocol and molecular networking can facilitate and accelerate the discovery of bioactive small molecules by targeting molecules of interest, while minimizing the use of toxic solvents.

Toxic Hazards Research Unit Annual Report: 1986

Science.gov (United States)

1987-04-01

mediated hemolysis by mercapto compounds. Journal of Applied Toxicology, Volume 6, Number 5, pages 336-370, 1986. Hydrophobic tributyltin ( TBT ...7 ~OF~ AAMRL-TR-87-020 NMRI-87-2 ’~LRES 4 Iq 1986 TOXIC HAZARDS RESEARCH UNIT ANNUAL REPORT WILLIAM E. HOUSTON, Ph.D. RAYMOND S. KUTZMAN, Ph.D...and is approved for publication. FOR THE COMMANDElRi BRUCE 0. STUART, Ph.D. Director, Toxic Hazards Division Harry G. Armstrong Aerospace Medical

Renal toxicity caused by oral use of medicinal plants: the yacon example.

Science.gov (United States)

de Oliveira, Rejane Barbosa; de Paula, Daniela Aparecida Chagas; Rocha, Bruno Alves; Franco, João José; Gobbo-Neto, Leonardo; Uyemura, Sérgio Akira; dos Santos, Wagner Ferreira; Da Costa, Fernando Batista

2011-01-27

Yacon [Smallanthus sonchifolius (Poepp. & Endl.) H. Robinson, Asteraceae] is an Andean species that has traditionally been used as an anti-diabetic herb in several countries around the world, including Brazil. Its hypoglycaemic action has recently been demonstrated in normal and diabetic rats. However, studies about the safety of prolonged oral consumption of yacon leaf extracts are lacking. Thus, this work was undertaken to evaluate the repeated-dose toxicity of three extracts from yacon leaves: the aqueous extract (AE) prepared as a tea infusion; the leaf-rinse extract (LRE), which is rich in sesquiterpene lactones (STLs); and a polar extract from leaves without trichomes, or polar extract (PE), which lacks STLs but is rich in chlorogenic acids (CGAs). The major classes of the compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling as well as comparison to standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The PE was rich in CGAs, but we did not detect any STLs. The AE and LRE showed the presence of STLs. The polar extract caused alterations in some biochemical parameters, but the animals did not show signs of behavioural toxicity or serious lesions in organs. Alterations of specific biochemical parameters in the blood (creatinine 7.0 mg/dL, glucose 212.0 mg/dL, albumin 2.8 g/dL) of rats treated with AE (10, 50 and 100 mg/kg) and LRE (10 and 100 mg/kg) pointed to renal damage, which was confirmed by histological analysis of the kidneys. The renal damage was associated with increased blood glucose levels after prolonged oral administration of the AE. This observation suggested that the hypoglycaemic effect observed after treatment for 30 days in an earlier study is reversible and was likely the result of renal injury caused by the toxicity of yacon. Because STLs were detected in both AE and LRE, there is strong evidence that these terpenoids are the main toxic

Contact toxicities of anuran skin alkaloids against the fire ant ( Solenopsis invicta)

Science.gov (United States)

Weldon, Paul J.; Cardoza, Yasmin J.; Vander Meer, Robert K.; Hoffmann, W. Clint; Daly, John W.; Spande, Thomas F.

2013-02-01

Nearly 500 alkaloids, representing over 20 structural classes, have been identified from the skin of neotropical poison frogs (Dendrobatidae). These cutaneous compounds, which are derived from arthropod prey of the frogs, generally are believed to deter predators. We tested the red imported fire ant ( Solenopsis invicta) for toxicosis following contact with 20 alkaloids (12 structural classes) identified from dendrobatids or other anurans. Individual ants forced to contact the dried residues of 13 compounds exhibited convulsions and/or reduced ambulation. We estimated the cutaneous concentrations of several compounds based on their reported recoveries from skin extracts of free-ranging frogs and our measurements of the skin surface areas of museum specimens. Pumiliotoxin 251D exhibited contact toxicity below its estimated cutaneous concentration in the Ecuadorian frog, Epipedobates anthonyi, an observation consistent with the hypothesized role of this compound in anuran chemical defense. Our results and those of a previous study of mosquitoes indicate that some anuran skin compounds function defensively as contact toxins against arthropods, permeating their exoskeleton.

Use of environmental health-risk analysis for managing toxic substances

International Nuclear Information System (INIS)

McKone, T.E.

1985-03-01

This paper presents a set of simple models used to assess health risks based on toxicity, environmental mobility and persistence. These models use a representative landscape in order to describe the steady-state distribution of arsenic, tritiated water, and TCDD as a result of continuous additions to soil. This information is used to assess potential exposures. Application of the screening model to three chemically different carcinogens reveals that the environmental health risk does not scale with direct measures of toxicity. As estimated here, the environmental health risk of TCDD relative to tritiated water and arsenic is roughly an order of magnitude less than its cancer potency relative to these compounds. The difference is attributable in large part to the immobility of TCDD relative to tritium and the lower persistence of TCDD compared to arsenic. The purpose is to present a simple procedure for using the relative behavior of toxic species under prototype conditions as a basis for risk management. 21 refs., 4 tabs

Methoxsalen-induced macular toxicity

Directory of Open Access Journals (Sweden)

Aditya Maitray

2017-01-01

Full Text Available Psoralen compounds such as methoxsalen are photosensitizer agents used in conjunction with ultraviolet A (UVA radiation exposure as photochemotherapy (Psoralens and ultraviolet-A therapy [PUVA therapy] for certain epidermal skin disorders such as psoriasis and vitiligo. Methoxsalen has been shown to be associated with premature cataract formation by forming adducts with lens proteins following oral administration and subsequent UVA exposure. Hence, the use of UV-filtering glasses is recommended during PUVA therapy sessions. Ocular tissues can be exposed to its photosensitizing effect with subsequent UV radiation exposure through sunlight if the patient was to be without protective eye glasses, potentially causing macular toxicity. Till date, there have been no reports in the literature of any posterior segment ocular toxicity arising from methoxsalen use. Here, we describe a case of a bilateral macular toxicity in a middle-aged male treated with methoxsalen for vitiligo.

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: kpsingh_52@yahoo.com; Gupta, Shikha

2014-03-15

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

In silico prediction of toxicity of non-congeneric industrial chemicals using ensemble learning based modeling approaches

International Nuclear Information System (INIS)

Singh, Kunwar P.; Gupta, Shikha

2014-01-01

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 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 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

Microbial transformations of natural organic compounds and radionuclides in subsurface environments

International Nuclear Information System (INIS)

Francis, A.J.

1985-10-01

A major national concern in the subsurface disposal of energy wastes is the contamination of ground and surface waters by waste leachates containing radionuclides, toxic metals, and organic compounds. Microorganisms play an important role in the transformation of organic compounds, radionuclides, and toxic metals present in the waste and affect their mobility in subsurface environments. Microbial processes involved in dissolution, mobilization, and immobilization of toxic metals under aerobic and anaerobic conditions are briefly reviewed. Metal complexing agents and several organic acids produced by microbial action affect mobilization of radionuclides and toxic metals in subsurface environments. Information on the persistence of and biodegradation rates of synthetic as well as microbiologically produced complexing agents is scarce but important in determining the mobility of metal organic complexes in subsoils. Several gaps in knowledge in the area of microbial transformation of naturally occurring organics, radionuclides, and toxic metals have been identified, and further basic research has been suggested. 31 refs., 1 fig., 3 tabs

Toxic neuropathies: Mechanistic insights based on a chemical perspective.

Science.gov (United States)

LoPachin, Richard M; Gavin, Terrence

2015-06-02

2,5-Hexanedione (HD) and acrylamide (ACR) are considered to be prototypical among chemical toxicants that cause central-peripheral axonopathies characterized by distal axon swelling and degeneration. Because the demise of distal regions was assumed to be causally related to the onset of neurotoxicity, substantial effort was devoted to deciphering the respective mechanisms. Continued research, however, revealed that expression of the presumed hallmark morphological features was dependent upon the daily rate of toxicant exposure. Indeed, many studies reported that the corresponding axonopathic changes were late developing effects that occurred independent of behavioral and/or functional neurotoxicity. This suggested that the toxic axonopathy classification might be based on epiphenomena related to dose-rate. Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences. Perhaps more importantly, we will discuss how knowledge of neurotoxicant chemical nature can guide molecular-level research toward a better, more rational understanding of mechanism. Our discussion will focus on HD, the neurotoxic γ-diketone metabolite of the industrial solvents n-hexane and methyl-n-butyl ketone. Early investigations suggested that HD caused giant neurofilamentous axonal swellings and eventual degeneration in CNS and PNS. However, as our review will point out, this interpretation underwent several iterations as the understanding of γ-diketone chemistry improved and more quantitative experimental approaches were implemented. The chemical concepts and design strategies discussed in this mini-review are broadly applicable to the mechanistic studies of other chemicals (e.g., n-propyl bromine, methyl methacrylate) that cause toxic neuropathies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mixture toxicity of the antiviral drug Tamiflu (oseltamivir ethylester) and its active metabolite oseltamivir acid

Energy Technology Data Exchange (ETDEWEB)

Escher, Beate I., E-mail: b.escher@uq.edu.au [University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Rd, Brisbane, Qld 4108 (Australia); Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Bramaz, Nadine; Lienert, Judit; Neuwoehner, Judith [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Straub, Juerg Oliver [F.Hoffmann-La Roche Ltd, Corporate Safety, Health and Environmental Protection, 4070 Basel (Switzerland)

2010-02-18

Tamiflu (oseltamivir ethylester) is an antiviral agent for the treatment of influenza A and B. The pro-drug Tamiflu is converted in the human body to the pharmacologically active metabolite, oseltamivir acid, with a yield of 75%. Oseltamivir acid is indirectly photodegradable and slowly biodegradable in sewage works and sediment/water systems. A previous environmental risk assessment has concluded that there is no bioaccumulation potential of either of the compounds. However, little was known about the ecotoxicity of the metabolite. Ester hydrolysis typically reduces the hydrophobicity and thus the toxicity of a compound. In this case, a zwitterionic, but overall neutral species is formed from the charged parent compound. If the speciation and predicted partitioning into biological membranes is considered, the metabolite may have a relevant contribution to the overall toxicity. These theoretical considerations triggered a study to investigate the toxicity of oseltamivir acid (OA), alone and in binary mixtures with its parent compound oseltamivir ethylester (OE). OE and OA were found to be baseline toxicants in the bioluminescence inhibition test with Vibrio fischeri. Their mixture effect lay between predictions for concentration addition and independent action for the mixture ratio excreted in urine and nine additional mixture ratios of OE and OA. In contrast, OE was an order of magnitude more toxic than OA towards algae, with a more pronounced effect when the direct inhibition of photosystem II was used as toxicity endpoint opposed to the 24 h growth rate endpoint. The binary mixtures in this assay yielded experimental mixture effects that agreed with predictions for independent action. This is consistent with the finding that OE exhibits slightly enhanced toxicity, while OA acts as baseline toxicant. Therefore, with respect to mixture classification, the two compounds can be considered as acting according to different modes of toxic action, although there are

EMISSIONS OF ORGANIC AIR TOXICS FROM OPEN ...

Science.gov (United States)

A detailed literature search was performed to collect and collate available data reporting emissions of toxic organic substances into the air from open burning sources. Availability of data varied according to the source and the class of air toxics of interest. Volatile organic compound (VOC) and polycyclic aromatic hydrocarbon (PAH) data were available for many of the sources. Data on semivolatile organic compounds (SVOCs) that are not PAHs were available for several sources. Carbonyl and polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofuran (PCDD/F) data were available for only a few sources. There were several sources for which no emissions data were available at all. Several observations were made including: 1) Biomass open burning sources typically emitted less VOCs than open burning sources with anthropogenic fuels on a mass emitted per mass burned basis, particularly those where polymers were concerned; 2) Biomass open burning sources typically emitted less SVOCs and PAHs than anthropogenic sources on a mass emitted per mass burned basis. Burning pools of crude oil and diesel fuel produced significant amounts of PAHs relative to other types of open burning. PAH emissions were highest when combustion of polymers was taking place; and 3) Based on very limited data, biomass open burning sources typically produced higher levels of carbonyls than anthropogenic sources on a mass emitted per mass burned basis, probably due to oxygenated structures r

Toxicity profile of labile preservative bronopol in water: The role of more persistent and toxic transformation products

International Nuclear Information System (INIS)

Cui Na; Zhang Xiaoxiang; Xie Qing; Wang Se; Chen Jingwen; Huang Liping; Qiao Xianliang; Li Xuehua; Cai Xiyun

2011-01-01

Transformation products usually differ in environmental behaviors and toxicological properties from the parent contaminants, and probably cause potential risks to the environment. Toxicity evolution of a labile preservative, bronopol, upon primary aquatic degradation processes was investigated. Bronopol rapidly hydrolyzed in natural waters, and primarily produced more stable 2-bromo-2-nitroethanol (BNE) and bromonitromethane (BNM). Light enhanced degradation of the targeted compounds with water site specific photoactivity. The bond order analysis theoretically revealed that the reversible retroaldol reactions were primary degradation routes for bronopol and BNE. Judging from toxicity assays and the relative pesticide toxicity index, these degradation products (i.e., BNE and BNM), more persistent and higher toxic than the parent, probably accumulated in natural waters and resulted in higher or prolonging adverse impacts. Therefore, these transformation products should be included into the assessment of ecological risks of non-persistent and low toxic chemicals such as the preservative bronopol. - The preservative bronopol is non-persistent and low toxic, but some transformation products can cause higher or prolonging adverse impacts.

Toxicity profile of labile preservative bronopol in water: The role of more persistent and toxic transformation products

Energy Technology Data Exchange (ETDEWEB)

Cui Na; Zhang Xiaoxiang; Xie Qing; Wang Se; Chen Jingwen; Huang Liping; Qiao Xianliang; Li Xuehua [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Cai Xiyun, E-mail: xiyuncai@dlut.edu.c [Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China)

2011-02-15

Transformation products usually differ in environmental behaviors and toxicological properties from the parent contaminants, and probably cause potential risks to the environment. Toxicity evolution of a labile preservative, bronopol, upon primary aquatic degradation processes was investigated. Bronopol rapidly hydrolyzed in natural waters, and primarily produced more stable 2-bromo-2-nitroethanol (BNE) and bromonitromethane (BNM). Light enhanced degradation of the targeted compounds with water site specific photoactivity. The bond order analysis theoretically revealed that the reversible retroaldol reactions were primary degradation routes for bronopol and BNE. Judging from toxicity assays and the relative pesticide toxicity index, these degradation products (i.e., BNE and BNM), more persistent and higher toxic than the parent, probably accumulated in natural waters and resulted in higher or prolonging adverse impacts. Therefore, these transformation products should be included into the assessment of ecological risks of non-persistent and low toxic chemicals such as the preservative bronopol. - The preservative bronopol is non-persistent and low toxic, but some transformation products can cause higher or prolonging adverse impacts.

Evaluation of toxic action of fluorides on agricultural plants

Directory of Open Access Journals (Sweden)

V. N. Grishko

2007-03-01

Full Text Available The toxicity of potassium fluoride, sodium fluoride and ammonium fluoride for pea, maize, oat and onion was studied. It was found that the level of the toxic influence had grown with increase of fluoride concentration in the media of growth (from 5 to 100 mg of F–/l. By increase of the toxic influence the agricultural crops are disposed in the following row: oat < onion < maize < pea. Ammonium fluoride demonstrates lesser toxicity, than potassium and sodium fluorides. Under low concentrations of fluoride compounds (5 and 10 mg of F–/l stimulation of roots growth is noted only for the oat.

Nicotine, aerosol particles, carbonyls and volatile organic compounds in tobacco- and menthol-flavored e-cigarettes.

Science.gov (United States)

Lee, Mi-Sun; LeBouf, Ryan F; Son, Youn-Suk; Koutrakis, Petros; Christiani, David C

2017-04-27

We aimed to assess the content of electronic cigarette (EC) emissions for five groups of potentially toxic compounds that are known to be present in tobacco smoke: nicotine, particles, carbonyls, volatile organic compounds (VOCs), and trace elements by flavor and puffing time. We used ECs containing a common nicotine strength (1.8%) and the most popular flavors, tobacco and menthol. An automatic multiple smoking machine was used to generate EC aerosols under controlled conditions. Using a dilution chamber, we targeted nicotine concentrations similar to that of exposure in a general indoor environment. The selected toxic compounds were extracted from EC aerosols into a solid or liquid phase and analyzed with chromatographic and spectroscopic methods. We found that EC aerosols contained toxic compounds including nicotine, fine and nanoparticles, carbonyls, and some toxic VOCs such as benzene and toluene. Higher mass and number concentrations of aerosol particles were generated from tobacco-flavored ECs than from menthol-flavored ECs. We found that diluted machine-generated EC aerosols contain some pollutants. These findings are limited by the small number of ECs tested and the conditions of testing. More comprehensive research on EC exposure extending to more brands and flavor compounds is warranted.

Acute and chronic systemic chromium toxicity.

Science.gov (United States)

Gad, S C

1989-10-01

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

Synthesis and Activity of Grape Wood Phytotoxins and Related Compounds

Directory of Open Access Journals (Sweden)

S. Perrin-Cherioux

2004-04-01

Full Text Available The synthesis of analogues and derivatives of two o-hydroxyphenylacetylenes, eutypine and sterehirsutinal, the main phytotoxins isolated from the culture medium of Eutypa lata and Stereum hirsutum, is reported. Two means of synthesis are described, based on cyclisation, oxidation, oxidative decarboxylation or reduction reactions, and producing o-hydroxyphenylacetylene or benzofuran derivatives. Some of these synthetic compounds were tested on grapevine callus in order to compare their toxicity with the natural analogues.

An exposure-based framework for grouping pollutants for a cumulative risk assessment approach: case study of indoor semi-volatile organic compounds.

Science.gov (United States)

Fournier, Kevin; Glorennec, Philippe; Bonvallot, Nathalie

2014-04-01

Humans are exposed to a large number of contaminants, many of which may have similar health effects. This paper presents a framework for identifying pollutants to be included in a cumulative risk assessment approach. To account for the possibility of simultaneous exposure to chemicals with common toxic modes of action, the first step of the traditional risk assessment process, i.e. hazard identification, is structured in three sub-steps: (1a) Identification of pollutants people are exposed to, (1b) identification of effects and mechanisms of action of these pollutants, (1c) grouping of pollutants according to similarity of their mechanism of action and health effects. Based on this exposure-based grouping we can derive "multi-pollutant" toxicity reference values, in the "dose-response assessment" step. The approach proposed in this work is original in that it is based on real exposures instead of a limited number of pollutants from a unique chemical family, as traditionally performed. This framework is illustrated by the case study of semi-volatile organic compounds in French dwellings, providing insights into practical considerations regarding the accuracy of the available toxicological information. This case study illustrates the value of the exposure-based approach as opposed to the traditional cumulative framework, in which chemicals with similar health effects were not always included in the same chemical class. Copyright © 2014 Elsevier Inc. All rights reserved.

Ligand efficiency based approach for efficient virtual screening of compound libraries.

Science.gov (United States)

Ke, Yi-Yu; Coumar, Mohane Selvaraj; Shiao, Hui-Yi; Wang, Wen-Chieh; Chen, Chieh-Wen; Song, Jen-Shin; Chen, Chun-Hwa; Lin, Wen-Hsing; Wu, Szu-Huei; Hsu, John T A; Chang, Chung-Ming; Hsieh, Hsing-Pang

2014-08-18

Here we report for the first time the use of fit quality (FQ), a ligand efficiency (LE) based measure for virtual screening (VS) of compound libraries. The LE based VS protocol was used to screen an in-house database of 125,000 compounds to identify aurora kinase A inhibitors. First, 20 known aurora kinase inhibitors were docked to aurora kinase A crystal structure (PDB ID: 2W1C); and the conformations of docked ligand were used to create a pharmacophore (PH) model. The PH model was used to screen the database compounds, and rank (PH rank) them based on the predicted IC50 values. Next, LE_Scale, a weight-dependant LE function, was derived from 294 known aurora kinase inhibitors. Using the fit quality (FQ = LE/LE_Scale) score derived from the LE_Scale function, the database compounds were reranked (PH_FQ rank) and the top 151 (0.12% of database) compounds were assessed for aurora kinase A inhibition biochemically. This VS protocol led to the identification of 7 novel hits, with compound 5 showing aurora kinase A IC50 = 1.29 μM. Furthermore, testing of 5 against a panel of 31 kinase reveals that it is selective toward aurora kinase A & B, with <50% inhibition for other kinases at 10 μM concentrations and is a suitable candidate for further development. Incorporation of FQ score in the VS protocol not only helped identify a novel aurora kinase inhibitor, 5, but also increased the hit rate of the VS protocol by improving the enrichment factor (EF) for FQ based screening (EF = 828), compared to PH based screening (EF = 237) alone. The LE based VS protocol disclosed here could be applied to other targets for hit identification in an efficient manner. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Comparison of the neurotoxicities between volatile organic compounds and fragrant organic compounds on human neuroblastoma SK-N-SH cells and primary cultured rat neurons

Directory of Open Access Journals (Sweden)

Yasue Yamada

2015-01-01

Full Text Available These are many volatile organic compounds (VOCs that are synthesized, produced from petroleum or derived from natural compounds, mostly plants. Fragrant and volatile organic compounds from plants have been used as food additives, medicines and aromatherapy. Several clinical and pathological studies have shown that chronic abuse of VOCs, mainly toluene, causes several neuropsychiatric disorders. Little is known about the mechanisms of neurotoxicity of the solvents. n-Octanal, nonanal, and 2-ethyl-1-hexanol, which are used catalyzers or intermediates of chemical reactions, are released into the environment. Essential oils have the functions of self-defense, sterilization, and antibiosis in plants. When volatile organic compounds enter the body, there is the possibility that they will pass through the blood–brain barrier (BBB and affect the central nervous system (CNS. However, the direct effects of volatile organic compounds on neural function and their toxicities are still unclear. We compared the toxicities of n-octanal, nonanal and 2-ethyl-1-hexanol with those of five naturally derived fragrant organic compounds (FOCs, linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and n-phenethyl alcohol. MTT assay of human neuroblastoma SK-N-SH cells showed that the IC50 values of linalool, cis-3-hexen-1-ol, isoamyl alcohol, n-propyl alcohol and phenethyl alcohol were 1.33, 2.3, >5, >5, and 2.39 mM, respectively, and the IC50 values of toluene, n-octanal, nonanal and 2-ethyl-1-hexanol were 850, 37.2, 8.31 and 15.1 μM, respectively. FOCs showed lower toxicities than those of VOCs. These results indicate that FOCs are safer than other compounds.

Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

International Nuclear Information System (INIS)

Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

2002-01-01

Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

Directory of Open Access Journals (Sweden)

Anju Ranga

2017-01-01

Full Text Available Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles.

Toxicities of triclosan, phenol, and copper sulfate in activated sludge.

Science.gov (United States)

Neumegen, Rosalind A; Fernández-Alba, Amadeo R; Chisti, Yusuf

2005-04-01

The effect of toxicants on the BOD degradation rate constant was used to quantitatively establish the toxicity of triclosan, phenol, and copper (II) against activated sludge microorganisms. Toxicities were tested over the following ranges of concentrations: 0-450 mg/L for phenol, 0-2 mg/L for triclosan, and 0-35 mg/L for copper sulfate (pentahydrate). According to the EC(50) values, triclosan was the most toxic compound tested (EC(50) = 1.82 +/- 0.1 mg/L), copper (II) had intermediate toxicity (EC(50) = 18.3 +/- 0.37 mg/L), and phenol was the least toxic (EC(50) = 270 +/- 0.26 mg/L). The presence of 0.2% DMSO had no toxic effect on the activated sludge. The toxicity evaluation method used was simple, reproducible, and directly relevant to activated sludge wastewater treatment processes.

Testing of toxicity based methods to develop site specific clean up objectives - phase 1: Toxicity protocol screening and applicability

International Nuclear Information System (INIS)

Hamilton, H.; Kerr, D.; Thorne, W.; Taylor, B.; Zadnik, M.; Goudey, S.; Birkholz, D.

1994-03-01

A study was conducted to develop a cost-effective and practical protocol for using bio-assay based toxicity assessment methods for remediation of decommissioned oil and gas production, and processing facilities. The objective was to generate site-specific remediation criteria for contaminated sites. Most companies have used the chemical-specific approach which, however, did not meet the ultimate land use goal of agricultural production. The toxicity assessment method described in this study dealt with potential impairment to agricultural crop production and natural ecosystems. Human health concerns were not specifically addressed. It was suggested that chemical-specific methods should be used when human health concerns exist. . Results showed that toxicity tests will more directly identify ecological stress caused by site contamination than chemical-specific remediation criteria, which can be unnecessarily protective. 11 refs., 7 tabs., 6 figs

Redox-Active Selenium Compounds—From Toxicity and Cell Death to Cancer Treatment

Directory of Open Access Journals (Sweden)

Sougat Misra

2015-05-01

Full Text Available Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.

"1H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

International Nuclear Information System (INIS)

Melvin, Steven D.; Habener, Leesa J.; Leusch, Frederic D.L.; Carroll, Anthony R.

2017-01-01

Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • "1H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

Chemical toxicity and radiological health detriment associated with the inhalation of various enrichments of uranium

International Nuclear Information System (INIS)

3C Limited, Queen Square House, 18-21 Queen Square, Bristol BS1 4NH (United Kingdom))" data-affiliation=" (SR3C Limited, Queen Square House, 18-21 Queen Square, Bristol BS1 4NH (United Kingdom))" >Bryant, P A

2014-01-01

The occupational risks associated with the chemical toxicity of uranium can be overlooked during the processing, handling and storage of the material, as the radioactivity of the material is often used alone to assess the health consequences of exposure to uranium compounds. This note provides a summary of the current United Kingdom occupational standards for uranium based on radiation dose and/or chemical toxicity with a particular focus on intake via inhalation. A simple model is subsequently presented to allow a comparison to be drawn between the occupational exposure standard for chemical toxicity and radiological dose limit. Using these data a set of suggested limits on occupational exposure to airborne uranium is proposed that indicate where the legal annual radiological dose limit for workers or the Health and Safety Executive occupational exposure standard for chemical toxicity are at risk of being breached. (note)

Probing the ToxCastTM Chemical Library for Predictive Signatures of Developmental Toxicity - Poster at Teratology Society Annual Meeting

Science.gov (United States)

EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesize that cell signaling pathways are primary targets for diverse environmental chemicals ...

Innovative technologies for removing toxic compounds from groundwater and air

International Nuclear Information System (INIS)

Rosocha, L.A.; Allen, G.R.; Anderson, G.K.; Bechtold, L.A.; Coogan, J.J.; Heck, H.G.; Kang, M.; McCulla, W.H.; Secker, D.A.; Smith, J.D.; Tennant, R.A.; Wantuck, P.J.

1992-01-01

Innovative waste treatment technologies are being developed to remove hazardous organic wastes from water and air. These technologies involve the generation of highly reactive free radicals and their reaction with organic compounds. Two efficient methods of producing these reactive free radicals are radiolysis and electrical-discharge plasmas. Radiolytic technology involves the irradiation of contaminated media with high-energy electron beams or x rays generated from the beams (megavolt energies, hundreds of kilorad doses). This process is best understood in aqueous solutions, in which sizable quantities of the free radicals e aq - , OH*, and H*, as well as the more stable oxidant H 2 0 2 , are produced. These highly reactive species react with organic contaminants to produce C0 2 , H 2 0, and salts, which are no longer hazardous. Nonequilibrium electrical-discharge plasmas involve the generation of copious quantities of reactive free radicals from the dissociation of molecular oxygen by energetic electrons in the gas-based discharge. One of the most promising technologies for plasma processing is based upon the ''silent electrical discharge'' that has proven to be industrially dependable for the generation of large quantities of ozone

Toxicity of copper chelates of azomethines and amino acids for Chlorella pyrenoidosa

Energy Technology Data Exchange (ETDEWEB)

Barashkov, G.K.; Rukhadze, E.G.; Talyzenkova, G.P.

1979-01-01

The authors have attempted to assess the toxicity of copper-containing compounds from the point of view of their interrelationship with the structural characteristics of the chelate compound and the structure of the ligand. The copper chelates of the azomethines tested may be provisionally divided into three types: A - complexes with N-alkly-azomethines; B - complexes with N-aryl-azomethines; C - binuclear complexes. Consideration was also given to chelates with aromatic and heterocyclic amino acids and to heteroligand chelates in which the copper atom coordinates azomethine and an amino acid simultaneously. Toxicity was determined by the method previously described and expressed as a critical concentration (C/sub cr/, mg Cu/liter) and in relative toxicity units (T/sub c/). The compounds investigated were obtained from the interaction between a bidentant ligand of an azomethine or anamino acid and copper acetate in a water-alcohol medium at pH 6-8. Since they are not very soluble in water, true solutions were obtained by using dimethyl sulfoxide.

Evaluation of the Potential Risk of Drugs to Induce Hepatotoxicity in Human—Relationships between Hepatic Steatosis Observed in Non-Clinical Toxicity Study and Hepatotoxicity in Humans-

Science.gov (United States)

Goda, Keisuke; Kobayashi, Akio; Takahashi, Akemi; Takahashi, Tadakazu; Saito, Kosuke; Maekawa, Keiko; Saito, Yoshiro; Sugai, Shoichiro

2017-01-01

In the development of drugs, we sometimes encounter fatty change of the hepatocytes (steatosis) which is not accompanied by degenerative change in the liver in non-clinical toxicity studies. In this study, we investigated the relationships between fatty change of the hepatocytes noted in non-clinical toxicity studies of compound X, a candidate compound in drug development, and mitochondrial dysfunction in order to estimate the potential risk of the compound to induce drug-induced liver injury (DILI) in humans. We conducted in vivo and in vitro exploratory studies for this purpose. In vivo lipidomics analysis was conducted to investigate the relationships between alteration of the hepatic lipids and mitochondrial dysfunction. In the liver of rats treated with compound X, triglycerides containing long-chain fatty acids, which are the main energy source of the mitochondria, accumulated. Accumulation of these triglycerides was considered to be related to the inhibition of mitochondrial respiration based on the results of in vitro mitochondria toxicity studies. In conclusion, fatty change of the hepatocytes (steatosis) in non-clinical toxicity studies of drug candidates can be regarded as a critical finding for the estimation of their potential risk to induce DILI in humans when the fatty change is induced by mitochondrial dysfunction. PMID:28417920

Toxicity of a plant based mosquito repellent/killer

Science.gov (United States)

Singh, Prakash Raj; Mohanty, Manoj Kumar

2012-01-01

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. PMID:23554562

Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides

Science.gov (United States)

Nowell, Lisa H.; Norman, Julia E.; Ingersoll, Christopher G.; Moran, Patrick W.

2016-01-01

Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole-sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n = 3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical

Environmental recovery by destruction of toxic organic compounds using electron beam accelerator

International Nuclear Information System (INIS)

Duarte, C.L; Sampa, M.H.O.; Rela, P.R.; Oikawa, H.

2001-01-01

The oxidation process has attracted many researchers because of the capacity to mineralise organic compounds. The most efficient oxidation is the use of OH radicals. There are various methods to generate OH radicals as the use of ozone, hydrogen peroxide and ultra-violet (AOP - Advanced Oxidation Process). The most simple and efficient method for generating OH radicals in situ is the interaction of ionizing radiation with water. The reactive species formed by the water irradiation are the reducing radical's solvated electron and H atoms and the oxidising radical hydroxyl OH. The reactive species will react with organic compounds in the water inducing their decomposition. The use of ionizing radiation has great ecological and technologies advantages, especially when compared to physical-chemical and biological methods. It degrades organic compounds, generating substances that are easily biodegraded without the necessity of adding chemical compounds. The purpose of the radiation treatment is the conversion of these substances to biodegradable compounds; sometimes the complete decomposition is not necessary for this conversion

Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs

International Nuclear Information System (INIS)

Yasuda, Shin; Idell, Steven; Fu Jian; Carter, Glendora; Snow, Rhodora; Liu, M.-C.

2007-01-01

The current study was designed to examine the role of sulfation in the metabolism of cigarette smoke toxicants and clarify whether these toxicants, by serving as substrates for the cytosolic sulfotransferases (SULTs), may interfere with the sulfation of key endogenous compounds. By metabolic labeling, [ 35 S]sulfated species were found to be generated and released into the media of HepG2 human hepatoma cells and primary human lung endothelial cells labeled with [ 35 S]sulfate in the presence of cigarette smoke extract (CSE). Concomitantly, several [ 35 S]sulfated metabolites observed in the medium in the absence of CSE either decreased or disappeared. Eleven previously prepared human cytosolic SULTs were tested for sulfating activity with CSE and known cigarette smoke toxicants as substrates. Activity data revealed SULT1A1, SULT1A2, SULT1A3, and SULT1C2 as major enzymes responsible for their sulfation. To examine their inhibitory effects on the sulfation of 17β-estradiol by SULT1A1, enzymatic assays were performed in the presence of three representative toxicant compounds, namely N-hydroxy-4-aminobiphenyl (N-OH-4-ABP), 4-aminobiphenyl (4-ABP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). IC 50 values determined for the sulfation of 17β-estradiol by SULT1A1 were 11.8 μM, 28.2 μM, and 500 μM, respectively, for N-OH-4-ABP, 4-ABP and PhIP. Kinetic analyses indicated that the mechanism underlying the inhibition of 17β-estradiol sulfation by these cigarette smoke toxicants is of a mixed competitive-noncompetitive type. Metabolic labeling experiments clearly showed inhibition of the production of [ 35 S]sulfated 17β-estradiol by N-OH-4-ABP in a concentration-dependent manner in HepG2 cells. Taken together, these results suggest that sulfation plays a significant role in the metabolism of cigarette smoke compounds. By serving as substrates for SULTs, cigarette smoke toxicants may interfere with the metabolism of 17β-estradiol and other endogenous

Ecological effects of low toxicity oil-based mud drilling in the Beatrice oilfield

Energy Technology Data Exchange (ETDEWEB)

Addy, J M; Hartley, J P; Tibbetts, P J.C.

1984-12-01

To investigate the effects of drilling discharges on the seabed fauna, surveys were carried out in the Beatrice oilfield after drilling 13 wells with water-based muds, and then after one and five further wells had been drilled using low toxicity oil-based muds. Localized benthic effects were found after the water-based mud drilling. After the use of oil-based muds, the nature of the effects was different, although there was little increase in the area involved. Possible reasons for this are discussed and burial and organic enrichment are suggested as the major influences. It is concluded that the use of low toxicity oil-based mud at Beatrice has resulted in only limited benthic effects, suggesting that the use of these muds is environmentally acceptable.

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

2012-01-01

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.

Simple test guidelines for screening oilspill sorbents for toxicity

International Nuclear Information System (INIS)

Blenkinsopp, S.A.; Sergy, G.; Doe, K.; Jackman, P.; Huybers, A.

1998-01-01

Environment Canada's Emergencies Science Division has established a program to develop a standard test method suitable for evaluating the toxicity of common sorbent materials. Sorbents are used to absorb or adsorb spilled oil and other hazardous materials. They vary widely in composition and packaging. They are often treated with oleophilic and hydrophobic compounds to improve performance and have been used in large quantities during oil spills. Until now, their potential toxicity has never been considered. Three tests have been evaluated to determine how appropriate they are in screening the toxicity of sorbents. Seven toxicity test recommendations for sorbents were presented. 7 refs., 3 tabs., 2 figs

Thermoregulatory responses to environmental toxicants: The interaction of thermal stress and toxicant exposure

International Nuclear Information System (INIS)

Leon, Lisa R.

2008-01-01

Thermal stress can have a profound impact on the physiological responses that are elicited following environmental toxicant exposure. The efficacy by which toxicants enter the body is directly influenced by thermoregulatory effector responses that are evoked in response to high ambient temperatures. In mammals, the thermoregulatory response to heat stress consists of an increase in skin blood flow and moistening of the skin surface to dissipate core heat to the environment. These physiological responses may exacerbate chemical toxicity due to increased permeability of the skin, which facilitates the cutaneous absorption of many environmental toxicants. The core temperature responses that are elicited in response to high ambient temperatures, toxicant exposure or both can also have a profound impact on the ability of an organism to survive the insult. In small rodents, the thermoregulatory response to thermal stress and many environmental toxicants (such as organophosphate compounds) is often biphasic in nature, consisting initially of a regulated reduction in core temperature (i.e., hypothermia) followed by fever. Hypothermia is an important thermoregulatory survival strategy that is used by small rodents to diminish the effect of severe environmental insults on tissue homeostasis. The protective effect of hypothermia is realized by its effects on chemical toxicity as molecular and cellular processes, such as lipid peroxidation and the formation of reactive oxygen species, are minimized at reduced core temperatures. The beneficial effects of fever are unknown under these conditions. Perspective is provided on the applicability of data obtained in rodent models to the human condition

Method of plasma etching Ga-based compound semiconductors

Science.gov (United States)

Qiu, Weibin; Goddard, Lynford L.

2012-12-25

A method of plasma etching Ga-based compound semiconductors includes providing a process chamber and a source electrode adjacent to the process chamber. The process chamber contains a sample comprising a Ga-based compound semiconductor. The sample is in contact with a platen which is electrically connected to a first power supply, and the source electrode is electrically connected to a second power supply. The method includes flowing SiCl.sub.4 gas into the chamber, flowing Ar gas into the chamber, and flowing H.sub.2 gas into the chamber. RF power is supplied independently to the source electrode and the platen. A plasma is generated based on the gases in the process chamber, and regions of a surface of the sample adjacent to one or more masked portions of the surface are etched to create a substantially smooth etched surface including features having substantially vertical walls beneath the masked portions.

Photoenhanced Toxicity of Petroleum to Aquatic Invertebrates and Fish: Review of State of the Science

Science.gov (United States)

Photoenhanced toxicity is a distinct mechanism of petroleum toxicity that is mediated by the interaction of solar radiation with specific polycyclic aromatic compounds (PACs) in oil. Phototoxicity is observed as a 2 to greater than 1000 fold increase in chemical toxicity to aqua...

Possibility of use of Azgir underground nuclear cavities for burial of sulfur and her toxic compounds - products of oil refining

International Nuclear Information System (INIS)

Akhmetov, E.Z.; Adymov, Zh.I.

1998-01-01

The intensive growth of production oil and gas in Western Kazakhstan increases ecological vulnerability of an environment and a fauna because of the pressure of negative consequences arising with production, refining and transportation of the oil raw material, and also because of pernicious influence of accompanying products and wastes of oil refining manufacture being chemically dangerous and toxic, requiring special conditions of the handling, warehousing and storage for provision of ecological safety. A problem of the reclamation, safe warehousing, storage and long-term disposal (burial) of such accompanying products and wastes, as for example, sulfur and its compounds till now is not solved. For example, the mass of the accumulated mountains of crystal sulfur makes on cautious calculations from 2 up to 3 million tonnes also creates real danger of the propagation and harmful influence on the environment. The neutralization of sulfur and its compounds means removal them from the active handling with an environment, i.e. creation of such conditions in which sulfur products for a long time cannot cause harm atmosphere, underground medium and waters, vegetative and animal world. For it is offered to use underground cavities in a salt dome raising Large Azgir and the funnel-shaped hollow in persalt rocks formed as a result of underground nuclear explosions, carried out in 1978-1979 years near village Azgir Atyrau province. The sulfur products is possible to place on a long safe storage in funnel-shaped hollow (the A9 platform) volume 1,5 million cubic meters, by keeping, if necessary, an possibility of their extraction for needs of the future generations or to remove in underground nuclear cavities in stone salt (the A8 and A11 platforms) total volume 330000 cubic meters, from which it is not provided in the future to take out the sulfur products. At this the sulfur is removed from an environment on a storage or burial in the inactive form, i.e. the sulfur products

Photometabolism of Heterocyclic Aromatic Compounds by Rhodopseudomonas palustris OU 11

Science.gov (United States)

Sasikala, C.; Ramana, C. V.; Rao, P. Raghuveer

1994-01-01

Rhodopseudomonas palustris OU 11 (ATCC 51186; DSM 7375) isolated from a pond of chemical industry effluent could anaerobically photometabolize heterocyclic aromatic compounds belonging to the pyridine and pyrazine groups only after a period of adaptation on pyrazinoic acid of 5 to 6 weeks. Growth on heterocyclic compounds was light dependent. The effects of various concentrations of heterocyclic compounds on growth suggest that higher concentrations of these compounds inhibit growth and are toxic. PMID:16349307

Anticoagulant rodenticide toxicity to non-target wildlife under controlled exposure conditions

Science.gov (United States)

Rattner, Barnett A.; Mastrota, F. Nicholas; van den Brink, Nico; Elliott, J.; Shore, R.; Rattner, B.

2018-01-01

Much of our understanding of anticoagulant rodenticide toxicity to non-target wildlife has been derived from molecular through whole animal research and registration studies in domesticated birds and mammals, and to a lesser degree from trials with captive wildlife. Using these data, an adverse outcome pathway identifying molecular initiating and anchoring events (inhibition of vitamin K epoxide reductase, failure to activate clotting factors), and established and plausible linkages (coagulopathy, hemorrhage, anemia, reduced fitness) associated with toxicity, is presented. Controlled exposure studies have demonstrated that second-generation anticoagulant rodenticides (e.g., brodifacoum) are more toxic than first- and intermediate-generation compounds (e.g., warfarin, diphacinone), however the difference in potency is diminished when first- and intermediate-generation compounds are administered on multiple days. Differences in species sensitivity are inconsistent among compounds. Numerous studies have compared mortality rate of predators fed prey or tissue containing anticoagulant rodenticides. In secondary exposure studies in birds, brodifacoum appears to pose the greatest risk, with bromadiolone, difenacoum, flocoumafen and difethialone being less hazardous than brodifacoum, and warfarin, coumatetralyl, coumafuryl, chlorophacinone and diphacinone being even less hazardous. In contrast, substantial mortality was noted in secondary exposure studies in mammals ingesting prey or tissue diets containing either second- or intermediate-generation compounds. Sublethal responses (e.g., prolonged clotting time, reduced hematocrit and anemia) have been used to study the sequelae of anticoagulant intoxication, and to some degree in the establishment of toxicity thresholds or toxicity reference values. Surprisingly few studies have undertaken histopathological evaluations to identify cellular lesions and hemorrhage associated with anticoagulant rodenticide exposure in non

Antidotes for poisoning by alcohols that form toxic metabolites.

Science.gov (United States)

McMartin, Kenneth; Jacobsen, Dag; Hovda, Knut Erik

2016-03-01

The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience. © 2015 The British Pharmacological Society.

Gut microbiota modulation of chemotherapy efficacy and toxicity.

Science.gov (United States)

Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

2017-06-01

Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

Nanomaterials in the Environment: Perspectives on in Vivo Terrestrial Toxicity Testing

Directory of Open Access Journals (Sweden)

Monique C. P. Mendonça

2017-10-01

Full Text Available Over the last decade, engineered nanomaterials (NMs brought a revolutionary development in many sectors of human life including electronics, paints, textiles, food, agriculture, and health care. However, the exponential growth in the number of NMs applications resulted in uncertainties regarding their environmental impacts. Currently, the common approach for assessing the toxicity of NMs such as, carbon—(fullerenes, single- and multi-walled carbon nanotubes, mineral—(gold and silver nanoparticles, cerium and zinc oxide, silicon and titanium dioxide, and organic-based NMs (dendrimers includes standard guidelines applied to all chemical compounds. Nevertheless, NMs differ from traditional materials as their physicochemical and surface properties influence the toxic rather than their composition alone. Considering such NMs specificities, adaptations in some methods are necessary to ensure that environmental and human health risks are accurately investigated. In this context, the focus of this mini-review is to summarize the current knowledge in nanotoxicology regarding relevant organisms and experimental assays for assessing the terrestrial toxicity of NMs.

Formation and elution of toxic compounds from sterilized medical products: toxic compound formation from irradiated products

International Nuclear Information System (INIS)

Shintani, Hideharu

1996-01-01

No formation of MDA was observed in chain-extended thermoplastic polyurethane (PU) when sterilized by autoclave or γ-ray irradiation. No formation of MDA was observed in nonchain-extended thermoplastic PU when sterilized by γ-ray irradiation. Less than 1 ppm MDA was produced in nonchain-extended thermoplastic PU sterilized by autoclave sterilization. Autoclave sterilization did not produce MDA in thermosetting PU potting material. MDA formation in potting material was promoted by γ-irradiation and increased with increasing irradiation at a quadratic equation of regression. MDA formation at 100 kGy irradiation is a few ppm and < 1 ppm at 25kGy irradiation, therefore the potential risk to human recipients was not significant. The elution of compounds other than MDA from potting material was more problematic. Solvent extracts from potting material presented mutagenicity in the absence of metabolic activity. MDA presented mutagenicity in the presence of metabolic activity, therefore MDA was not the mutagenic trigger. The chemical and biological characteristics of the specific mutagens required to identify in a further study. Negative promotion of MDA formation and a less presence of mutagen in autoclave sterilized potting material indicated that autoclave sterilization was preferable. (Author)

Drug metabolism and pharmacokinetic diversity of ranunculaceae medicinal compounds.

Science.gov (United States)

Hao, Da-Cheng; Ge, Guang-Bo; Xiao, Pei-Gen; Wang, Ping; Yang, Ling

2015-01-01

The wide-reaching distributed angiosperm family Ranunculaceae has approximately 2200 species in around 60 genera. Chemical components of this family include several representative groups: benzylisoquinoline alkaloid (BIA), ranunculin, triterpenoid saponin and diterpene alkaloid, etc. Their extensive clinical utility has been validated by traditional uses of thousands of years and current evidence-based medicine studies. Drug metabolism and pharmacokinetic (DMPK) studies of plant-based natural products are an indispensable part of comprehensive medicinal plant exploration, which could facilitate conservation and sustainable utilization of Ranunculaceae pharmaceutical resources, as well as new chemical entity development with improved DMPK parameters. However, DMPK characteristics of Ranunculaceaederived medicinal compounds have not been summarized. Black cohosh (Cimicifuga) and goldenseal (Hydrastis) raise concerns of herbdrug interaction. DMPK studies of other Ranunculaceae genera, e.g., Nigella, Delphinium, Aconitum, Trollius, and Coptis, are also rapidly increasing and becoming more and more clinically relevant. In this contribution, we highlight the up-to-date awareness, as well as the challenges around the DMPK-related issues in optimization of drug development and clinical practice of Ranunculaceae compounds. Herb-herb interaction of Ranunculaceae herb-containing traditional Chinese medicine (TCM) formula could significantly influence the in vivo pharmacokinetic behavior of compounds thereof, which may partially explain the complicated therapeutic mechanism of TCM formula. Although progress has been made on revealing the absorption, distribution, metabolism, excretion and toxicity (ADME/T) of Ranunculaceae compounds, there is a lack of DMPK studies of traditional medicinal genera Aquilegia, Thalictrum and Clematis. Fluorescent probe compounds could be promising substrate, inhibitor and/or inducer in future DMPK studies of Ranunculaceae compounds. A better

Essential Oils of Hyptis pectinata Chemotypes: Isolation, Binary Mixtures and Acute Toxicity on Leaf-Cutting Ants.

Science.gov (United States)

Feitosa-Alcantara, Rosana B; Bacci, Leandro; Blank, Arie F; Alves, Péricles B; Silva, Indira Morgana de A; Soares, Caroline A; Sampaio, Taís S; Nogueira, Paulo Cesar de L; Arrigoni-Blank, Maria de Fátima

2017-04-12

Leaf-cutting ants are pests of great economic importance due to the damage they cause to agricultural and forest crops. The use of organosynthetic insecticides is the main form of control of these insects. In order to develop safer technology, the objective of this work was to evaluate the formicidal activity of the essential oils of two Hyptis pectinata genotypes (chemotypes) and their major compounds on the leaf-cutting ants Acromyrmex balzani Emery and Atta sexdens rubropilosa Forel. Bioassays of exposure pathways (contact and fumigation) and binary mixtures of the major compounds were performed. The major compounds identified in the essential oils of H. pectinata were β-caryophyllene, caryophyllene oxide and calamusenone. The essential oils of H. pectinata were toxic to the ants in both exposure pathways. Essential oils were more toxic than their major compounds alone. The chemotype calamusenone was more toxic to A. balzani in both exposure pathways. A. sexdens rubropilosa was more susceptible to the essential oil of the chemotype β-caryophyllene in both exposure pathways. In general, the binary mixtures of the major compounds resulted in additive effect of toxicity. The essential oils of H. pectinata is a raw material of great potential for the development of new insecticides.

Characteristic vibrational frequencies of toxic polychlorinated dibenzo-dioxins and -furans

International Nuclear Information System (INIS)

Patrizi, Barbara; Cumis, Mario Siciliani de; Viciani, Silvia; D’Amato, Francesco; Foggi, Paolo

2014-01-01

Highlights: • Database reporting FT-IR spectra for 13 of the 17 toxic PCDDs and PCDFs congeners. • Use of FT-IR database for quantification of toxic PCDD/Fs in complex matrix. • Monitoring of dioxin emissions from waste incinerators. - Abstract: The possibility to monitor in real-time the emission of dioxins produced by incineration of waste or by industrial processes is nowadays a necessity considering the high toxicity of these compounds, their persistence in the environment and their ability to bio-accumulate in the food chain. Recently it has been demonstrated the potentiality of detecting dioxins in carbon tetrachloride via MIR Quantum Cascade Lasers. A fundamental step in real time monitoring of dioxins emission is the possibility to recognize the most toxic congeners within complex mixtures and at low concentrations. Taking into account the lack of spectroscopic data about these very toxic environmental pollutants and the necessity to monitor their emissions we have recorded infrared spectra of 13 of the 17 most toxic congeners of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs) dissolved in carbon tetrachloride. In this way we have obtained a small database that we have used to test the ability of a linear regression algorithm to recognize each congener and its relative concentration in complex mixtures of these compounds

Characteristic vibrational frequencies of toxic polychlorinated dibenzo-dioxins and -furans

Energy Technology Data Exchange (ETDEWEB)

Patrizi, Barbara, E-mail: patrizi@lens.unifi.it [LENS, University of Florence, Via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); CNR, Istituto Nazionale di Ottica, Largo Enrico Fermi 6, 50125 Firenze (Italy); Cumis, Mario Siciliani de; Viciani, Silvia; D’Amato, Francesco [CNR, Istituto Nazionale di Ottica, Largo Enrico Fermi 6, 50125 Firenze (Italy); Foggi, Paolo [LENS, University of Florence, Via Nello Carrara 1, 50019 Sesto Fiorentino (Italy); CNR, Istituto Nazionale di Ottica, Largo Enrico Fermi 6, 50125 Firenze (Italy); Università degli Studi di Perugia, Dipartimento di Chimica, Via Elce di Sotto 8, 06123 Perugia (Italy)

2014-06-01

Highlights: • Database reporting FT-IR spectra for 13 of the 17 toxic PCDDs and PCDFs congeners. • Use of FT-IR database for quantification of toxic PCDD/Fs in complex matrix. • Monitoring of dioxin emissions from waste incinerators. - Abstract: The possibility to monitor in real-time the emission of dioxins produced by incineration of waste or by industrial processes is nowadays a necessity considering the high toxicity of these compounds, their persistence in the environment and their ability to bio-accumulate in the food chain. Recently it has been demonstrated the potentiality of detecting dioxins in carbon tetrachloride via MIR Quantum Cascade Lasers. A fundamental step in real time monitoring of dioxins emission is the possibility to recognize the most toxic congeners within complex mixtures and at low concentrations. Taking into account the lack of spectroscopic data about these very toxic environmental pollutants and the necessity to monitor their emissions we have recorded infrared spectra of 13 of the 17 most toxic congeners of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs) dissolved in carbon tetrachloride. In this way we have obtained a small database that we have used to test the ability of a linear regression algorithm to recognize each congener and its relative concentration in complex mixtures of these compounds.

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

Energy Technology Data Exchange (ETDEWEB)

Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

2013-10-15

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

International Nuclear Information System (INIS)

Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.; Stedman, Donald B.; Wang, Huijun; Will, Yvonne

2013-01-01

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary

EPA Toxicologists Focus Innovative Research on PFAS Compounds

Science.gov (United States)

EPA researchers have partnered with researchers at the National Toxicology Program to develop a tiered testing approach to quickly generate toxicity and kinetic information for approximately 75 PFAS compounds.

Performance Evaluation of Frequency Transform Based Block Classification of Compound Image Segmentation Techniques

Science.gov (United States)

Selwyn, Ebenezer Juliet; Florinabel, D. Jemi

2018-04-01

Compound image segmentation plays a vital role in the compression of computer screen images. Computer screen images are images which are mixed with textual, graphical, or pictorial contents. In this paper, we present a comparison of two transform based block classification of compound images based on metrics like speed of classification, precision and recall rate. Block based classification approaches normally divide the compound images into fixed size blocks of non-overlapping in nature. Then frequency transform like Discrete Cosine Transform (DCT) and Discrete Wavelet Transform (DWT) are applied over each block. Mean and standard deviation are computed for each 8 × 8 block and are used as features set to classify the compound images into text/graphics and picture/background block. The classification accuracy of block classification based segmentation techniques are measured by evaluation metrics like precision and recall rate. Compound images of smooth background and complex background images containing text of varying size, colour and orientation are considered for testing. Experimental evidence shows that the DWT based segmentation provides significant improvement in recall rate and precision rate approximately 2.3% than DCT based segmentation with an increase in block classification time for both smooth and complex background images.

{sup 1}H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

Energy Technology Data Exchange (ETDEWEB)

Melvin, Steven D., E-mail: s.melvin@griffith.edu.au [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Habener, Leesa J. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Leusch, Frederic D.L. [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Carroll, Anthony R. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia)

2017-03-15

Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • {sup 1}H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

Influence of physicochemical properties of beryllium particles on cultured cell toxicity

International Nuclear Information System (INIS)

Finch, G.L.; Brooks, A.L.; Hoover, M.D.; Cuddihy, R.G.

1988-01-01

The toxicity of beryllium oxide (BeO)), beryllium metal, and beryllium sulfate (BeSO 4 ) was studied in two cell lines, Chinese hamster ovary cells (CHO) and lung epithelial cells (LEC). Beryllium oxide particles were prepared at either 500 or 1000 deg. C, and two different particle sizes of beryllium metal were used. Following a 20-h exposure to beryllium compounds, cells were grown in culture to quantitate cloning ability relative to controls as a measure of cell killing, The LEC cultures were more sensitive to beryllium cytotoxicity than the CHO cells. When expressed on the basis of the mass of material added to the cultures, the order of toxicity was BeSO 4 ≥ 500 deg. C -BeO > 1000 deg. C -BeO > Be metal (small) Be metal (large). When cytotoxic effects were expressed on the basis of particulate surface rather than mass, the relative differences in toxicity between compounds was decreased. The order of toxicity was Be metal (small) ∼ Be metal (large) ∼ 500 deg. C-BeO ∼ 1000 deg. C-BeO. These data indicate that solubility influences beryllium toxicity to short-term cell cultures. (author)

Soil-based screening for iron toxicity tolerance in rice using pots

Directory of Open Access Journals (Sweden)

Mouritala Sikirou

2016-10-01

Full Text Available The objective of this study was to assess the reliability of pot-based screening method for iron (Fe toxicity tolerance in rice using soils from hot spots. Five lowland rice varieties with known reaction to Fe toxicity were grown in pots in a screen house for three seasons. Fe-toxic soils from two hot spot fields – Edozighi, Nigeria and Niaouli, Benin were used and soil from Africa Rice Center (AfricaRice experimental farm, Cotonou, Benin was included as control. Leaf bronzing score (LBS was determined at different stages, and grain yield was determined at maturity. Heritability was estimated using data across the three seasons. High heritability was recorded for LBS and grain yield. Grain yield reduction in stress treatment relative to control varied from 15 to 56% depending on the variety and soil. Bao Thai, Suakoko 8, and WITA 4 had better performance under Fe toxicity in terms of LBS, yield and relative yield reduction, whereas Bouake 189 and IR64 had poorer performance. Grain yield and LBS were significantly correlated but negatively at 60 days after sowing (DAS. Overall, the results found in this experiment were consistent with previous field studies. Therefore, pot screening using soils from hot spots can be used by rice breeding programs to reliably assess Fe toxicity tolerance ex situ.

Synthesis, Properties Characterization and Applications of Various Organobismuth Compounds

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Jingfei Luan

2011-05-01

Full Text Available Organobismuth chemistry was emphasized in this review article due to the low price, low toxicity and low radioactivity characteristics of bismuth. As an environmentally-friendly class of organometallic compounds, different types of organobismuth compounds have been used in organic synthesis, catalysis, materials, etc. The synthesis and property characterization of many organobismuth compounds had been summarized. This review article also presented a survey of various applications of organobismuth compounds in organic transformations, as reagents or catalysts. The reactivity, reaction pathways and mechanisms of reactions with organobismuths were discussed. Less common and limiting aspects of organobismuth compounds were also briefly mentioned.

Temperature determines toxicity: Bisphenol A reduces thermal tolerance in fish

International Nuclear Information System (INIS)

Little, Alexander G.; Seebacher, Frank

2015-01-01

Bisphenol A (BPA) is a ubiquitous pollutant around the globe, but whether environmental concentrations have toxic effects remains controversial. BPA interferes with a number of nuclear receptor pathways, including several that mediate animal responses to environmental input. Because thermal acclimation is regulated by these pathways in fish, we hypothesized that the toxicity of BPA would change with ambient temperature. We exposed zebrafish (Danio rerio) to ecologically relevant and artificially high concentrations of BPA at two acclimation temperatures, and tested physiological responses at two test temperatures that corresponded to acclimation temperatures. We found ecologically relevant concentrations of BPA (20 μg l −1 ) impair swimming performance, heart rate, muscle and cardiac SERCA activity and gene expression. We show many of these responses are temperature-specific and non-monotonic. Our results suggest that BPA pollution can compound the effects of climate change, and that its effects are more dynamic than toxicological assessments currently account for. - Highlights: • Whether environmental levels of BPA have toxic effects on local ecology remains controversial. • We show that ecological concentrations of BPA impair physiological performance in fish. • We also show that the toxic effects of BPA are temperature-specific and non-monotonic with dose. • BPA pollution will likely compound the effects of climate change, and vice-versa. • The toxic effects of BPA appear to be more dynamic than toxicological assessments account for. - BPA pollution is likely to compound the effects of climate change, and climate change may worsen the effects of BPA exposure. Its effects are likely to be more dynamic than toxicological assessments currently account for

Determination of sulfur compounds in hydrotreated transformer base oil by potentiometric titration.

Science.gov (United States)

Chao, Qiu; Sheng, Han; Cheng, Xingguo; Ren, Tianhui

2005-06-01

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.

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

Science.gov (United States)

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

2009-01-01

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

Acute toxicity of fire control chemicals to Daphnia magna(Straus) and Selenastrum capricornutum(Printz)

Science.gov (United States)

McDonald, Susan F.; Hamilton, Steven J.; Buhl, Kevin J.; Heisinger, James F.

1996-01-01

Acute toxicity tests were conducted exposingDaphnia magnaStraus (daphnid) in soft and hard reconstituted waters (hardness 42 and 162 mg/liter as CaCO3, respectively), andSelenastrum capricornutumPrintz (algae) in ASTM algal assay medium (hardness 15 mg/liter as CaCO3) to fire retardants Fire-Trol GTS-R, Fire-Trol LCG-R, and Phos-Chek D75-F, and foam suppressants Phos-Chek WD-881 and Silv-Ex. The chemicals were slightly toxic to practically harmless to daphnids and moderately toxic to algae. Water quality did not consistently alter the toxicity of the test chemicals to daphnids. The most toxic chemical to daphnids was Silv-Ex (48-hr EC507 mg/liter in soft and hard waters), whereas the least toxic chemical to daphnids was Fire-Trol LCG-R (48-hr EC50848 mg/liter in soft water, 813 mg/liter in hard water). The most toxic chemical to algae was Fire-Trol LCG-R (96-hr IC5010 mg/liter), and the least toxic chemical was Phos-Chek D75-F (96-hr IC5079 mg/liter). Un-ionized ammonia concentrations near the EC50or IC50value in tests with the Fire-Trol compounds were frequently equal to or above reported LC50un-ionized ammonia concentrations. Un-ionized ammonia concentrations in tests with Phos-Chek D75-F were low, thus other toxic components present in the compounds probably contributed to the toxicity. When compared to the daphnids tested in ASTM soft water, the Fire-Trol compounds were most toxic to algae, whereas Phos-Chek D75-F and the foam suppressants were most toxic to daphnids. The results of these tests are comparable to those obtained from research conducted in other laboratories with the same species and similar chemicals. Accidental entry of fire-fighting chemicals into aquatic environments could adversely affect algae and aquatic invertebrates, thus disrupting ecosystem function.

Molecular toxicity mechanism of nanosilver

Directory of Open Access Journals (Sweden)

Danielle McShan

2014-03-01

Full Text Available Silver is an ancient antibiotic that has found many new uses due to its unique properties on the nanoscale. Due to its presence in many consumer products, the toxicity of nanosilver has become a hot topic. This review summarizes recent advances, particularly the molecular mechanism of nanosilver toxicity. The surface of nanosilver can easily be oxidized by O2 and other molecules in the environmental and biological systems leading to the release of Ag+, a known toxic ion. Therefore, nanosilver toxicity is closely related to the release of Ag+. In fact, it is difficult to determine what portion of the toxicity is from the nano-form and what is from the ionic form. The surface oxidation rate is closely related to the nanosilver surface coating, coexisting molecules, especially thiol-containing compounds, lighting conditions, and the interaction of nanosilver with nucleic acids, lipid molecules, and proteins in a biological system. Nanosilver has been shown to penetrate the cell and become internalized. Thus, nanosilver often acts as a source of Ag+ inside the cell. One of the main mechanisms of toxicity is that it causes oxidative stress through the generation of reactive oxygen species and causes damage to cellular components including DNA damage, activation of antioxidant enzymes, depletion of antioxidant molecules (e.g., glutathione, binding and disabling of proteins, and damage to the cell membrane. Several major questions remain to be answered: (1 the toxic contribution from the ionic form versus the nano-form; (2 key enzymes and signaling pathways responsible for the toxicity; and (3 effect of coexisting molecules on the toxicity and its relationship to surface coating.

Rethinking developmental toxicity testing: Evolution or revolution?

NARCIS (Netherlands)

Scialli, Anthony R; Daston, George; Chen, Connie; Coder, Prägati S; Euling, Susan Y; Foreman, Jennifer; Hoberman, Alan M; Hui, Julia; Knudsen, Thomas; Makris, Susan L; Morford, LaRonda; Piersma, Aldert H; Stanislaus, Dinesh; Thompson, Kary E

2018-01-01

Current developmental toxicity testing adheres largely to protocols suggested in 1966 involving the administration of test compound to pregnant laboratory animals. After more than 50 years of embryo-fetal development testing, are we ready to consider a different approach to human developmental

Fourier-transform infrared spectroscopy as a novel approach to providing effect-based endpoints in duckweed toxicity testing.

Science.gov (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

2017-02-01

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. © 2016 SETAC.

Understanding mechanisms of toxicity: Insights from drug discovery research

International Nuclear Information System (INIS)

Houck, Keith A.; Kavlock, Robert J.

2008-01-01

Toxicology continues to rely heavily on use of animal testing for prediction of potential for toxicity in humans. Where mechanisms of toxicity have been elucidated, for example endocrine disruption by xenoestrogens binding to the estrogen receptor, in vitro assays have been developed as surrogate assays for toxicity prediction. This mechanistic information can be combined with other data such as exposure levels to inform a risk assessment for the chemical. However, there remains a paucity of such mechanistic assays due at least in part to lack of methods to determine specific mechanisms of toxicity for many toxicants. A means to address this deficiency lies in utilization of a vast repertoire of tools developed by the drug discovery industry for interrogating the bioactivity of chemicals. This review describes the application of high-throughput screening assays as experimental tools for profiling chemicals for potential for toxicity and understanding underlying mechanisms. The accessibility of broad panels of assays covering an array of protein families permits evaluation of chemicals for their ability to directly modulate many potential targets of toxicity. In addition, advances in cell-based screening have yielded tools capable of reporting the effects of chemicals on numerous critical cell signaling pathways and cell health parameters. Novel, more complex cellular systems are being used to model mammalian tissues and the consequences of compound treatment. Finally, high-throughput technology is being applied to model organism screens to understand mechanisms of toxicity. However, a number of formidable challenges to these methods remain to be overcome before they are widely applicable. Integration of successful approaches will contribute towards building a systems approach to toxicology that will provide mechanistic understanding of the effects of chemicals on biological systems and aid in rationale risk assessments

Evaluation of the treatment efficiencies of paper mill whitewaters in terms of organic composition and toxicity

International Nuclear Information System (INIS)

Latorre, Anna; Malmqvist, Asa; Lacorte, Silvia; Welander, Thomas; Barcelo, Damia

2007-01-01

The efficiency of several lab scale treatments (aerobic, anaerobic and ozone or combination of these) was evaluated using two packaging board mill whitewaters. The effect of the different treatments on the elimination of the organic load, the chemical oxygen demand (COD) and the toxicity was tested as well as the relationship between these parameters. Biocides, phenolic compounds, surfactants, plasticiziers and wood extractives were identified in untreated and treated whitewaters by liquid chromatography coupled with mass spectrometry (LC-MS) or gas chromatography coupled with mass spectrometry (GC-MS). A strong dependency on the water type and treatment efficiency was observed, being the combination of anaerobic and aerobic treatments the best option to reduce the organic contaminants in these waters, although in some cases, the toxicity did not decrease. However, ozone as post-treatment permitted a further reduction of organic compounds, toxicity and COD. - Aerobic and anaerobic treatments remove organic compounds in paper mill effluents but toxicity remains

Toxicity identification evaluation of cosmetics industry wastewater.

Science.gov (United States)

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

2013-01-15

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

Toxicity of selenium (Na sub 2 SeO sub 3 ) and mercury (HgCl sub 2 ) on the planarian Dugesia gonocephala

Energy Technology Data Exchange (ETDEWEB)

Congiu, A.M.; Casu, S.; Ugazio, G. (Istituto di Genetica (Italy))

1989-10-01

The toxicity of selenium (Na{sub 2}SeO{sub 3}) and mercury (HgCl{sub 2}) was determined by using a freshwater planarian which is particularly sensitive to pollution, and belongs to a fissiparous breed of Dugesia gonocephala. The mortality and fissiparity frequency of the subjects were studied. They were exposed to intense treatments (48 hours) or for medium to long periods of time (21 days) to either the single compounds or a combination of both, and were fed or fasting. The lethal effect of sodium selenite is correlated to the food intake, whereas the toxicity of mercurous chloride is probably the result of a fixative effect which does not depend on feeding. The 21-day treatment with the first compound has a non-negligible lethal effect which is probably due to an accumulation phenomenon. At doses where an antioxidant effect prevails, fissiparity is stimulated. On the other hand, the second compound reduces reproduction frequency to half the base values. Compared to the Paracentrotus lividus, the Dugesia gonocephala offers various advantages concerning toxicological experiments; besides being easier to handle in the laboratory, it is available all year round and is not subject to seasonal cycles. It is also more susceptible to the toxic effect of mercury, which is a common and highly toxic pollutant, than the sea urchin.

Translation of Japanese Noun Compounds at Super-Function Based MT System

Science.gov (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.

Toxicity of coal-tar and asphalt sealants to eastern newts, Notophthalmus viridescens

Energy Technology Data Exchange (ETDEWEB)