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At least 145 records · Page 8Linked to original sources
PubMed2005

Influence of glyphosate and its formulation (Roundup) on the toxicity and bioavailability of metals to Ceriodaphnia dubia.

This study examined the toxicological interaction between glyphosate (or its formulation, Roundup) and several heavy metals to a freshwater cladoceran, Ceriodaphnia dubia. We demonstrated that all binary combinations of Roundup and metals (Cd, Cu, Cr, Ni, Pb, Se and Zn) exhibited "less than additive" mixture toxicity, with 48-h LC50 toxic unit > 1. Addition of glyphosate alone could significantly reduce the acute toxicity of Ag, Cd, Cr, Cu, Ni, Pb and Zn (but not Hg and Se). The ratio between glyphosate and metal ions was important in determining the mitigation of metal toxicity by glyphosate. A bioaccumulation study showed that in the presence of glyphosate the uptake of some metals (e.g. Ag) was halted but that of others (e.g. Hg) was increased significantly. Therefore, our study strongly suggests that glyphosate and its commercial formulations can control the toxicity as well as the bioavailability of heavy metals in aquatic ecosystems where both groups of chemicals can co-occur.

Adsorption↗
PubMed2002

Evaluation of the joint-action toxicity of binary mixtures of heavy metals against the mangrove periwinkle Tympanotonus fuscatus var radula (L.).

The joint-action toxicity of binary mixtures of heavy metal compounds prepared in predefined ratios of 4:1, 3:2, 1:1, 2:3, and 1:4 (wt/wt) of Zn:Cu, Zn:Cd, and Cd:Cu, respectively, and tested against the mangrove periwinkle Tympanotonus fuscatus were carried out in laboratory bioassays. The interactions between binary mixtures showed significant departures from the action of the individual constituent metals when acting singly. On the basis of the models such as isobole representations, synergistic ratios (SRs), and concentration-addition models used for the joint-action evaluations, the interactions between the constituent metals in the various test proportions of the mixtures were largely in conformity with the models of antagonism. Furthermore, in most of the test combinations of the binary mixtures, the Zn compound was found to consistently reduce the toxic effect of Cu and Cd compounds when tested jointly against T. fuscatus. The possibility of utilizing the observed antagonistic interactions between Zn(2+) and Cd(2+) in the management of Cd-contaminated waterbodies was discussed and the synergistic ratio model was singled out as a better candidate model for joint-action toxicity evaluations, which are aimed at establishing environmental safe limits of pollutants.

Animals↗
PubMed2004

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

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

Aliivibrio fischeri↗
PubMed2001

Adenylate kinase as a virulence factor of Pseudomonas aeruginosa.

Adenylate kinase (AK; ATP:AMP phosphotransferase, EC 2.7.4.3) is a ubiquitous enzyme that contributes to the homeostasis of adenine nucleotides in eukaryotic and prokaryotic cells. AK catalyzes the reversible reaction Mg. ATP + AMP <--> Mg. ADP + ADP. In this study we show that AK secreted by the pathogenic strains of Pseudomonas aeruginosa appears to play an important role in macrophage cell death. We purified and characterized AK from the growth medium of a cystic fibrosis isolate strain of P. aeruginosa 8821 and hyperproduced it as a fusion protein with glutathione S-transferase. We demonstrated enhanced macrophage cell death in the presence of both the secreted and recombinant purified AK and its substrates AMP plus ATP or ADP. These data suggested that AK converts its substrates to a mixture of AMP, ADP, and ATP, which are potentially more cytotoxic than ATP alone. In addition, we observed increased macrophage killing in the presence of AK and ATP alone. Since the presence of ATPase activity on the macrophages was confirmed in the present work, external macrophage-effluxed ATP is converted to ADP, which in turn can be transformed by AK into a cytotoxic mixture of three adenine nucleotides. Evidence is presented in this study that secreted AK was detected in macrophages during infection with P. aeruginosa. Thus, the possible role of secreted AK as a virulence factor is in producing and keeping an intact pool of toxic mixtures of AMP, ADP, and ATP, which allows P. aeruginosa to exert its full virulence.

Adenine Nucleotides↗
PubMed2005

Significance testing of synergistic/antagonistic, dose level-dependent, or dose ratio-dependent effects in mixture dose-response analysis.

In ecotoxicology, the state of the art for effect assessment of chemical mixtures is through multiple dose-response analysis of single compounds and their combinations. Investigating whether such data deviate from the reference models of concentration addition and/or independent action to identify overall synergism or antagonism is becoming routine. However, recent data show that more complex deviation patterns, such as dose ratio-dependent deviation and dose level-dependent deviation, need to be addressed. For concentration addition, methods to detect such deviation patterns exist, but they are stand-alone methods developed separately in literature, and conclusions derived from these analyses are therefore difficult to compare. For independent action, hardly any methods to detect such deviations from this reference model exist. This paper describes how these well-established mixture toxicity principles have been incorporated in a coherent data analysis procedure enabling detection and quantification of dose level-and dose ratio-specific synergism or antagonism from both the concentration addition and the independent action models. Significance testing of which deviation pattern describes the data best is carried out through maximum likelihood analysis. This analysis procedure is demonstrated through various data sets, and its applicability and limitations in mixture research are discussed.

Animals↗
PubMedDate not supplied

Synthesis, identification, and acute toxicity of some N-alkyl derivatives of 3,4-methylenedioxyamphetamine.

A series of N-alkyl derivatives of 3,4-methylenedioxyamphetamine (MDA) was prepared in an effort to characterize these potential drugs of abuse. These secondary amines were synthesized via reductive amination of the corresponding ketone with alkylamines. The ultraviolet absorption spectra for these compounds produced almost equally intense absorbance at 234 and 285 nm. The compounds were separated by liquid chromatography using reverse phase (C18) procedures with a ternary mobile phase mixture. Toxicity studies showed all of the compounds to have LD50 values similar to N-methyl MDA (MDMA).

3,4-Methylenedioxyamphetamine↗
PubMed2002

Application of a mixture of glycol polyethylenes for the preparation of microcorrosion casts--an observation.

Preparation of microcorrosion casts that can be used for observation in SEM is a laborious, time-consuming procedure. The authors paid particular attention to the process of dissection of the microcorrosion casts. This prompted the authors to reconstruct the plastic mass, produced by the firm Gurr (Great Britain) in the 1970s, which was used by them in previous research to immerse the cast in order to minimise the damage. By using easily obtainable polyethylene glycols, characterised by different physical and chemical features, in order to obtain smooth surface of the section, a low-toxic mixture was composed, which protected the microcorrosion casts sufficiently and did not interfere with the physical and chemical properties of the cast.

Cadaver↗
PubMed1976

Exocellular proteases of Serratia marcescens and their toxicity to larvae of Galleria mellonella.

Out of 18 strains of Serratia marcescens producing exocellular proteases the strain Serratia marcescens CCEB 415 was selected according to preliminary experiments. It could be shown that the train exhibits proteolytic activity reaching up to 10 TU per 1 ml of the culture filtrate in a medium with gelatine and peptone. Two proteolytic enzyme could be demonstrated by means of specific inhibitors EDTA and diisopropyfluorophosphate: metalprotease with optimum activity at pH 7.5 and serine protease with pH optimum of 10.9. The enzymes were purified on Sephadex and DEAE cellulose columns and by means of gel electrophoresis. However, it was not possible to separate them. The optimum temperature for activity of the mixture of the two enzymes was 50degrees C, molecular weight varied around 37000 (according to gel filtration); certain kinetic characteristics of their activity were determined. Excess subtrate (casein) inhibited activity of the enzyme mixture. Toxicity of proteases expressed as LD50 units equals 78 - 10(3) TU per larva of Galleria mellonella.

Animals↗
PubMed2003

The toxicity of metal mixtures to the estuarine mysid Neomysis integer (Crustacea: Mysidacea) under changing salinity.

Water quality criteria are mainly based on data obtained in toxicity tests with single toxicants. Several authors have demonstrated that this approach may be inadequate as the joint action of the chemicals is not taken into account. In this study, the combined effects of six metals on the European estuarine mysid Neomysis integer (Leach, 1814) were examined. Acute 96-h toxicity tests were performed with mercury, copper, cadmium, nickel, zinc and lead, and this as single compounds and as a mixture of all six. The concentrations of the individual metals of the equitoxic mixtures were calculated using the concentration-addition model. The 96-h LC50's for the single metals, at a salinity of 5 per thousand, ranged from 6.9 to 1140 microg/l, with the following toxicity ranking: Hg>Cd>Cu>Zn>Ni>Pb. Increasing the salinity from 5 to 25 per thousand resulted in lower toxicity and lower concentrations of the free ion (as derived from speciation calculations) for all metals. This salinity effect was strongest for cadmium and lead and could be attributed to complexation with chloride ions. The toxicity of nickel, copper and zinc was affected to a smaller extent by salinity. The 96-h LC50 for mercury was the same for both salinities. In order to evaluate the influence of changing salinity conditions on the acute toxicity of metal mixtures, tests were performed at different salinities (5, 10, 15 and 25 per thousand ). The 96-h LC50 value (1.49 T.U.) of the metal mixture, at a salinity of 5 per thousand, was clearly lower than the expected value (6 T.U.) based on the non-additive hypothesis, thus confirming the additive effect of these metals in the marine/estuarine environment. Changing salinity had a profound effect on the toxicity of the mixture. The toxicity clearly decreased with increasing salinity until 15 per thousand. Higher salinities (25 per thousand ) had no further influence on the 96-h LC50 of the mixture which is situated at a value between 4.4 and 4.6. Finally, the relative sensitivity to the selected metals was compared with the relative sensitivity of the commonly used mysid Americamysis (=Mysidopsis) bahia.

Animals↗
PubMed2003

Aquatic ecotoxicity of pharmaceuticals including the assessment of combination effects.

To evaluate the ecotoxicological potential of ten prescription drugs against aquatic organisms from different taxonornical classes, a set of biotests were performed using the cladoceran Daphnia magna, the chlorophyte Desmodesmus subspicatus and the macrophyte Lemna minor. Endpoints were immobilisation for Daphnia and inhibition of the average growth rate for Desmodesmus and Lemna. For most of the substances, toxicities were moderate, with EC(50)s in the range from 10 to 100 mgl(-1) or even far above, whereas Lemna was the most sensitive test species in the majority of all tested compounds. Tests with combinations of various pharmaceuticals revealed stronger effects than expected from the effects measured singly. Clofibrinic acid and Carbamazepine have been found to act by a non-specific mode of action (non-polar narcosis), and with Daphnia the combination effect of these substances followed the concept of concentration addition, while in the algae test the concept of independent action could be used to calculate the mixture toxicity. The anti-inflammatory drugs Diclofenac and Ibuprofen have also been found to act unspecific by non-polar narcosis and to follow the concept of concentration addition in the algal test as well as in the Daphnia test. The measured toxicities of the tested pharmaceuticals shows that acute effect of single substances in the aquatic environment are very unlikely. But we should keep in mind that considerable combination effects can occur and that toxicity data from chronic studies are needed to assess the environmental risk of drug residues.

Animals↗
PubMed1987

Preparation and performance of bispecific F(ab' gamma)2 antibody containing thioether-linked Fab' gamma fragments.

A simple and efficient method is described for the production of pure bispecific F(ab' gamma)2 heterodimers, in which the individual antibody Fab' gamma fragments are joined via a stable thioether linkage. Hybrid molecules were constructed from both mouse monoclonal and rabbit polyclonal antibodies with equal efficiency, in the combinations mouse-rabbit and mouse-mouse. Peptic F(ab' gamma)2 fragments from the two chosen antibodies were first reduced to provide Fab' gamma SH. The SH groups on one of the Fab' gamma SH partners were then fully alkylated with o-phenylenedi-maleimide to provide free maleimide groups. Finally the two preparations, Fab' gamma mal and Fab' gamma SH, combined under conditions which allowed cross-linking of the maleimide and SH groups and avoided reoxidation of SH groups. The major product isolated from the reaction mixture after chromatography was always the F(ab' gamma)2 heterodimer (50 to 70%), other products being unreacted Fab' gamma and trace amounts of putative F(ab' gamma)3. Immunochemical analysis revealed that the thioether-linked F(ab' gamma)2 molecules were essentially all heterodimers, most of which had been joined via their Fd chains. The dual specificity of F(ab' gamma)2 heterodimers was tested functionally in three systems: 1) the combination (anti-idiotype + anti-phycoerythrin) linked L2C cells to the fluorochrome phycoerythrin, allowing fluorescence analysis; 2) the combination (anti-idiotype + anti-saporin) linked L2C cells to the ribosome-inactivating protein saporin, and transformed a subtoxic dose of saporin into a highly toxic mixture which prevented further protein synthesis by L2C cells; and 3) the combination of anti-idiotype with 3G8 (antibody to the Fc gamma receptor CD16) subjected L2C cells to cytotoxic attack by human mononuclear effectors.

Animals↗
PubMed2002

Toxicity of metal mixtures to a tropical freshwater alga (Chlorella sp): the effect of interactions between copper, cadmium, and zinc on metal cell binding and uptake.

The individual and combined effects of copper, cadmium, and zinc on the cell division rate of the tropical freshwater alga Chlorella sp. were determined over 48 to 72 h. Metal mixtures were prepared based on multiples of their single-metal median effective concentration (EC50) values, i.e., toxic units (TU) using a triangular mixture design with five toxicant levels (0, 0.75, 1.0, 1.25, and 1.5 TU). Single-metal EC50 values after a 72-h exposure were 0.11, 0.85, and 1.4 microM for copper, cadmium, and zinc, respectively. Significant interactions were observed for all metal combinations after 48 and 72 h. An equitoxic mixture of Cu + Cd was more than concentration additive (synergistic) to the growth of Chlorella sp., while combinations of Cu + Zn, Cd + Zn, and Cu + Cd + Zn were all less than concentration additive or were antagonistic. To determine the effect of each metal on the uptake of the other, extracellular (membrane-bound) and intracellular metal concentrations, both alone and in mixtures, were compared. The increased growth inhibition observed for mixtures of Cu + Cd was due to higher concentrations of cell-bound and intracellular copper in the presence of cadmium compared with copper alone (i.e., cadmium-enhanced copper uptake). In contrast, both extra- and intracellular cadmium concentrations were reduced in the presence of copper. In mixtures of Cu + Zn, copper also inhibited the binding and cellular uptake of zinc, which resulted in decreased toxicity. Zinc had no appreciable effect on the uptake of copper by Chlorella sp. Our results suggest that all three metals share some common uptake and transport sites on Chlorella cells and that copper out competes both cadmium and zinc for cell binding. Determination of metal cell distribution coefficients (K(d)) confirmed that K(d) values for cadmium and zinc in single-metal exposures decreased in the presence of copper.

Cadmium↗
PubMed2003

Predictability of combined effects of eight chloroacetanilide herbicides on algal reproduction.

Chloroacetanilides are pre-emergence herbicides for the control of annual grasses and broadleaf weeds. As a result of their extensive use, residues are often found in surface waters. Observed simultaneous occurrence of different chloroacetanilide herbicides gives reason for concern about potential combination effects on aquatic non-target organisms. This study aimed to clarify whether joint effects of various chloroacetanilide herbicides may be predictable from knowledge of concentration-response relationships of single substances. Whether the chloroacetanilides all share the same mode of action is unclear. Therefore we investigated the predictive value of two alternative concepts for the prediction of combined effects: concentration addition, which assumes a similar mode of action, and independent action, which is based on the idea of a dissimilar mode of action of the mixture components. Eight chloroacetanilides (acetochlor, alachlor, butachlor, dimethachlor, metazachlor, metolachlor, pretilachlor and propachlor) were experimentally tested for their individual as well as for their combined effects in mixtures on the reproduction of the green alga Scenedesmus vacuolatus. Individual chloroacetanilides impaired algal reproduction, with EC50 values ranging from 3 to 232 microg litre(-1). The differences in EC50 values were strongly correlated with the lipophilicities of the compounds. Effects of chloroacetanilide mixtures were considerably higher than those of the individual components: a complete inhibition of algal reproduction was observed when every mixture component was present in a concentration that would cause only 5% effect if applied singly. However, the combined effects proved to be predictable by using the concept of concentration addition. The alternative concept, independent action, distinctly underestimated the mixture toxicity. These findings (1) indicate a similar mechanism of action of chloroacetanilides in algae and (2) reinforce the view that concentration addition is a reasonable assumption for the predictive hazard assessment of groups of similarly acting herbicides.

Acetamides↗
PubMed1985

Interaction of solid-phase gangliosides with tetanus toxin and toxoid.

Tetanus toxin has been fractionated on a column of silica beads coated with a ganglioside mixture. Toxicity and affinity of the fractions for brain membranes increased with their affinity for the column. The toxicity recovered with the nonabsorbed fraction was less than 5% with respect to the unfractionated toxin or its firmly bound moiety. Tetanus toxoid yielded less toxic or nontoxic fractions with different affinities for the column. Accordingly, binding of tetanus toxoid to brain membranes was partially preserved under mild toxoiding with formaldehyde. It is concluded that binding to gangliosides is a necessary, but not a sufficient, precondition for the pharmacological activity of tetanus toxin and its derivatives.

Animals↗
PubMed1985

Sublethal effects of simulated pulp mill effluents on the respiration and energy metabolism of rainbow trout (Salmo gairdneri).

Rainbow trout were exposed to 0.08 X 96-hr LC50 concentration of simulated unbleached (KME-Sa) and bleached (KME-Sa + CP) kraft pulp mill effluents. A sulfate soap preparation (Sa) with and without added chlorophenols (CP) was used as the toxicant mixture. The lipid content of white muscle increased in both test groups, and its protein content decreased in the KME-Sa-treated group. The ammonia excretion rate also decreased in both test groups. These results show that there was a shift from protein to lipid metabolism. On the other hand, apart from a slight hypoglycemia, only minor changes were observed in the carbohydrate metabolism. The overall effects on blood respiratory properties were functionally insignificant. However, the effects of kraft mill effluent with and without chlorophenols were qualitatively dissimilar in several respects.

Animals↗
PubMed1988

Subchronic metabolic effects and toxicity of a simulated pulp mill effluent on juvenile lake trout, Salmo trutta m. lacustris.

Juvenile lake trout (Salmo trutta m. lacustris) were exposed for 7 weeks to 0.05X and 0.2X 96-hr LC50 concentrations of simulated bleached kraft pulp mill effluent (KME - Sa + CP). A sulfate soap preparation, composed mainly of resin and fatty acids, with added chlorophenols (CP, tri-, tetra-, and penta-CP) was used as the toxicant mixture. Concentrations of free CP in plasma and free and conjugated CP in bile were proportional to their concentrations in the water. The greatest total gradient between bile and water CP was 5.2 X 10(4) for pentachlorophenol. The activity of a liver polysubstrate monooxygenase (PSMO) system, assayed with three model substrates, increased 40 to 67% due to KME - Sa + CP. However, the increase was not directly dependent on the exposure concentration. In contrast to PSMO, activities of conjugating enzymes (p-nitrophenol UDP-glucuronosyl and glutathione transferases) were decreased in the liver. Increased concentration of glutathione was noted in the liver and kidney. In addition, a small (9%) but significant decrease in blood hemoglobin concentration was observed at the higher exposure concentration. Although growth rate of lake trout was markedly decreased due to KME - Sa + CP, hydromineral balance and carbohydrate metabolism in fish were unaffected, indicating possible physiological compensation. On the other hand, lethality tests with lake trout preexposed to KME - Sa + CP at 0.2 X LC50 revealed decreased tolerance, whereas at the lower exposure concentration it was unchanged. We therefore conclude that various physiological adjustments in trout during subchronic exposures were not adaptive in terms of short-term tolerance.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2006

The fathead minnow in aquatic toxicology: past, present and future.

This paper reviews the roles of the fathead minnow (Pimephales promelas) as a small fish model in the field of aquatic toxicology. The species has been (and is) extensively used both for regulatory testing and research, especially in North America. For example, tests with the fathead minnow, ranging from 48-h lethality through partial and full life-cycle assays, are routinely used for regulatory programs aimed at assessing potential risks of new chemicals such as high-production volume materials and pesticides, as well as impacts of complex mixtures like effluents. The species also has been used for a wide variety of research applications focused on topics like the development of quantitative structure-activity relationship models, mixture toxicity, extrapolation of the effects of chemicals across species, and understanding the results of laboratory assays relative to impacts in the field. Attributes of the fathead minnow also make it an excellent model for addressing new challenges in aquatic toxicology, including identification of sensitive life-stages/endpoints for chemicals with differing modes/mechanisms of action, predicting population-level effects based on data collected from lower levels of biological organization, and exploring/understanding the emerging role of genomics in research and regulation.

Animals↗
PubMed2006

Antagonistic effects of methyl-mercury and PCB153 on PC12 cells after a combined and simultaneous exposure.

The study of interactions for those substances which tend to accumulate in food and affect the nervous system appears to be a fundamental point to characterize the combined exposure in vitro. In this study we included two food contaminants which are known neurotoxicants: methyl-mercury (Me-Hg) and the ortho-substituted PCB 153. PC12 cells were treated with Me-Hg (range 1e-7, 2e-6 M) and PCB153 (range 1e-5, 4e-4 M) in single and combined synchronous experiments and a mathematical model was set up according to the Loewe additivity criterion to evaluate the level of interaction between toxicants, using viability as end-point. At some concentrations (Me-Hg 5e-7 M and PCB153 1e-4 and 2e-4 M; Me-Hg 1e-6M and PCB153 5e-5 M; Me-Hg 1e-7 M and PCB153 4e-4 M), a statistically significant antagonist effect was observed. No interaction was observed for other combinations. The analysis of other toxicological parameters known to be modified in single exposure experiments (TBARS and intra-cellular dopamine) confirmed the viability results. The results of our work represent a starting point to generate novel information on the interactions between PCB153 and Me-Hg in vitro, as well as a new relevant experimental and mathematical approach useful to investigate the effects of different toxicant mixtures.

Animals↗