Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Mixture toxicity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

Combinations of Azadirachta indica and Cedrus deodara oil with piperonyl butoxide, MGK-264 and Embelia ribes against Lymnaea acuminata.

The binary and tertiary combinations of plant-derived molluscicides Azadirachta indica and Cedrus deodara oil with synergists MGK-264, piperonyl butoxide (PB) and fruit powder of Embelia ribes were used against the Lymnaea acuminata. It was observed that the toxic effects of these mixtures were time- and dose-dependent. The binary and tertiary mixtures of plant-derived molluscicides with synergists were more toxic with respect to the single treatment of the plant-derived molluscicides. Maximum synergistic action in binary and tertiary combinations was found in A. indica + C. deodara oil and A. indica+ PB + C. deodara in 1:7 and 1:5:7 ratio, respectively.

Animals↗

Toxicity of the chlordane metabolite oxychlordane in female rats: clinical and histopathological changes.

Due to widespread usage of the pesticide chlordane until the 1980's, this toxic and persistent mixture has accumulated in the food chain. The Arctic acts as a global sink for these and other persistent organic pollutants, which bioaccumulate in the marine and freshwater food chains. As a result, humans consuming diets high in Arctic fish and marine mammal fat can ingest higher levels of chlordane contaminants than humans consuming "southern" diets. The most abundant constituents of the chlordane mixture are trans-chlordane, cis-chlordane, trans-nonachlor, cis-nonachlor and heptachlor; oxychlordane is the major metabolite of the chlordanes and nonachlors. In humans the predominant chlordane-related contaminants detected in breast milk and adipose tissues are trans-nonachlor and oxychlordane. The present studies were undertaken to provide toxicological data on oxychlordane for the purpose of clarifying target organ toxicity and risks to human health associated with ingesting contaminated foods. Female rats were gavaged with oxychlordane at doses ranging from 0.01 to 10 mg/kg body weight/day for up to 28 days. In terms of general toxicity oxychlordane had a steep dose-response curve: 10 mg/kg oxychlordane was acutely toxic and 1 mg/kg oxychlordane caused no measurable effects. Weight loss, reduced feed consumption and thymic atrophy were the hallmarks of acute oxychlordane toxicity. At lower doses rats showed signs of hepatic changes indicative of microsomal enzyme induction. Oxychlordane was more bioaccumulative and was toxic at levels approximately 8 times lower than trans-nonachlor and cis-nonachlor. Thus, ingestion of trans-nonachlor and related chlordane contaminants in foods results in the formation of a metabolite that is more toxic and bioaccumulative than the parent contaminants.

Administration, Oral↗

Targeting the over-expressed urokinase-type plasminogen activator receptor on glioblastoma multiforme.

A recombinant fusion protein targeting the urokinase-type plasminogen activator receptor (uPAR) and delivering a potent catalytic toxin has the advantage of simultaneously targeting both over-expressed uPAR on glioblastoma cells and on the tumor neovasculature. Such a hybrid protein was synthesized consisting of the noninternalizing amino-terminal fragment (ATF) of urokinase-type plasminogen activator (uPA) for binding, and the catalytic portion of diphtheria toxin (DT) for killing, and the translocation enhancing region (TER) of DT for internalization. The protein was highly selective for human glioblastoma in vitro and in vivo. In vivo, this DT/ATF hybrid called DTAT caused the regression of small subcutaneous uPAR-expressing tumors with minimal toxicity to critical organs. In vitro, DTAT killed only uPAR-positive glioblastoma cell lines and human endothelial cells in the form of the HUVEC cell line. Killing was selective and blockable with specific antibody. DTAT was highly effective against tumor cells cultured from glioblastoma multiforme patients and in vitro mixing experiments combining DTAT with DTIL13 another highly effective anti-glioblastoma agent showed that the mixture was as toxic as the most potent immunotoxin. In this article, we review our progress to date with DTAT.

Animals↗

Modeling of Copper(II), Cadmium(II), and Lead(II) Adsorption on Red Mud from Metal-EDTA Mixture Solutions.

The adsorption of toxic heavy metal cations, i.e., Cu(II), Cd(II), and Pb(II), from metal-EDTA mixture solutions on a composite adsorbent having a heterogeneous surface, i.e., bauxite waste red mud, has been investigated and modeled with the aid of a modified surface complexation approach in respect to pH and complexant dependency of heavy metal adsorption. EDTA was selected as the modeling ligand in view of its wide usage as an anthropogenic chelating agent and abundance in natural waters. The adsorption experiments were conducted for metal salts (nitrates), metal-EDTA complexes alone, or in mixtures containing (metal+metal-EDTA). The adsorption equilibrium constants for the metal ions and metal-EDTA complexes were calculated. For all studied cases, the solid adsorbent phase concentrations of the adsorbed metal and metal-EDTA complexes were found by using the derived model equations with excellent compatibility of experimental and theoretically generated adsorption isotherms. The model was useful for metal and metal-EDTA mixture solutions either at their natural pH of equilibration with the sorbent, or after pH elevation with NaOH titration up to a certain pH. Thus adsorption of every single species (M(2+) or MY(2-)) or of possible mixtures (M(2+)+MY(2-)) at natural pH or after NaOH titration could be calculated by the use of simple quadratic model equations, once the initial concentrations of the corresponding species, i.e., [M(2+)](0) or [MY(2-)](0), were known. The compatibility of theoretical and experimental data pairs of adsorbed species concentrations was verified by means of nonlinear regression analysis. The findings of this study can be further developed so as to serve environmental risk assessment concerning the expansion of a heavy metal contaminant plume with groundwater move ment in soil consisting of hydrated-oxide type minerals. Copyright 2000 Academic Press.

Journal Article↗

The effect of combinations of Fusarium mycotoxins (deoxynivalenol, zearalenone and fumonisin B1) on growth of brewing yeasts.

The interactive effect of combinations of the Fusarium mycotoxins deoxynivalenol (DON), zearalenone (ZEA) and fumonisin B1 (FB1) on growth of brewing yeasts was examined. Yeast growth was assessed by measurement of dry weight or relative growth, cell number, viability and conductance change of the growth medium using direct and indirect methods. The interactive effect of a combination of these mycotoxins was subject to the ratio of toxins in the mixture and the toxicity of individual toxins on yeast growth. When a combination of mycotoxins at low concentration was added into the growth medium, no significant inhibitory effect on growth was observed compared to controls. However, when a combination of high concentrations of DON and ZEA which individually inhibited yeast growth was examined, the interactive effect was shown to pass from antagonism to synergism depending on the ratio of the toxins in the mixture. As a synergistic interaction between these Fusarium mycotoxins was observed only at high concentrations, which were far higher than would be expected in good quality grain, they are not a concern when related to yeast growth under the brewing conditions studied.

Beer↗

Study on subchronic toxicity of chlorine dioxide and by-products in water.

Subchronic toxicity of the mixture of ClO2, ClO2- and ClO3- in water on rat was studied through feeding test for 90 days. Statistical analyses of variance on weight gained, food utilization efficiency, indexes of blood and serum, liver/bodyweight and kidney/bodyweight ratios, and histopathological examination on liver and kidney were carried out. The results showed that solution of ClO2 and its by-products ClO2- and ClO3- at a concentration of 553 mg/L was not toxic.

Alanine Transaminase↗

The genetic basis of adaptation to copper pollution in Drosophila melanogaster.

Introduction: Heavy metal pollutants can have long lasting negative impacts on ecosystem health and can shape the evolution of species. The persistent and ubiquitous nature of heavy metal pollution provides an opportunity to characterize the genetic mechanisms that contribute to metal resistance in natural populations. Methods: We examined variation in resistance to copper, a common heavy metal contaminant, using wild collections of the model organism Drosophila melanogaster. Flies were collected from multiple sites that varied in copper contamination risk. We characterized phenotypic variation in copper resistance within and among populations using bulked segregant analysis to identify regions of the genome that contribute to copper resistance. Results and Discussion: Copper resistance varied among wild populations with a clear correspondence between resistance level and historical exposure to copper. We identified 288 SNPs distributed across the genome associated with copper resistance. Many SNPs had population-specific effects, but some had consistent effects on copper resistance in all populations. Significant SNPs map to several novel candidate genes involved in refolding disrupted proteins, energy production, and mitochondrial function. We also identified one SNP with consistent effects on copper resistance in all populations near CG11825, a gene involved in copper homeostasis and copper resistance. We compared the genetic signatures of copper resistance in the wild-derived populations to genetic control of copper resistance in the Drosophila Synthetic Population Resource (DSPR) and the Drosophila Genetic Reference Panel (DGRP), two copper-naïve laboratory populations. In addition to CG11825, which was identified as a candidate gene in the wild-derived populations and previously in the DSPR, there was modest overlap of copper-associated SNPs between the wild-derived populations and laboratory populations. Thirty-one SNPs associated with copper resistance in wild-derived populations fell within regions of the genome that were associated with copper resistance in the DSPR in a prior study. Collectively, our results demonstrate that the genetic control of copper resistance is highly polygenic, and that several loci can be clearly linked to genes involved in heavy metal toxicity response. The mixture of parallel and population-specific SNPs points to a complex interplay between genetic background and the selection regime that modifies the effects of genetic variation on copper resistance.

Drosophila↗

Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment.

Commercial polychlorinated biphenyls (PCBs) and environmental extracts contain complex mixtures of congeners that can be unequivocally identified and quantitated. Some PCB mixtures elicit a spectrum of biochemical and toxic responses in humans and laboratory animals and many of these effects resemble those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic hydrocarbons, which act through the aryl hydrocarbon (Ah)-receptor signal transduction pathway. Structure-activity relationships developed for PCB congeners and metabolites have demonstrated that several structural classes of compounds exhibit diverse biochemical and toxic responses. Structure-toxicity studies suggest that the coplanar PCBs, namely, 3,3',4,4'-tetrachlorobiphenyl (tetraCB), 3,3',4,4',5-pentaCB, 3,3',4,4',5,5'-hexaCB, and their monoortho analogs are Ah-receptor agonists and contribute significantly to the toxicity of the PCB mixtures. Previous studies with TCDD and structurally related compounds have utilized a toxic equivalency factor (TEF) approach for the hazard and risk assessment of polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) congeners in which the TCDD or toxic TEQ = sigma([PCDFi x TEFi]n)+sigma([PCDDi x TEFi]n) equivalent (TEQ) of a mixture is related to the TEFs and concentrations of the individual (i) congeners as indicated in the equation (note: n = the number of congeners). Based on the results of quantitative structure-activity studies, the following TEF values have been estimated by making use of the data available for the coplanar and monoortho coplanar PCBs: 3,3',4,4',5-pentaCB, 0.1; 3,3',4,4',5,5'-hexaCB, 0.05; 3,3',4,4'-tetraCB, 0.01; 2,3,3',4,4'-pentaCB, 0.001; 2,3',4,4',5-pentaCB, 0.0001; 2,3,3',4,4',5-hexaCB, 0.0003; 2,3,3',4,4',5'-hexaCB, 0.0003; 2',3,4,4',5-pentaCB, 0.00005; and 2,3,4,4',5-pentaCB, 0.0002. Application of the TEF approach for the risk assessment of PCBs must be used with considerable caution. Analysis of the results of laboratory animal and wildlife studies suggests that the predictive value of TEQs for PCBs may be both species- and response-dependent because both additive and nonadditive (antagonistic) interactions have been observed with PCB mixtures. In the latter case, the TEF approach would significantly overestimate the toxicity of a PCB mixture. Analysis of the rodent carcinogenicity data for Aroclor 1260 using the TEF approach suggests that this response is primarily Ah-receptor-independent. Thus, risk assessment of PCB mixtures that uses cancer as the endpoint cannot solely utilize a TEF approach and requires more quantitative information on the individual congeners contributing to the tumor-promoter activity of PCB mixtures.

Adipose Tissue↗

Public health guidance values for chemical mixtures: current practice and future directions.

Agency for Toxic Substances and Disease Registry (ATSDR) utilizes chemical-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. The MRLs are derived based on the data compiled from current worldwide literature searches and presented in ATSDR's toxicological profiles. These documents profile not only individual chemicals, but also groups of chemically related compounds and chemical mixtures. ATSDR took several approaches when developing MRLs for chemical mixtures. In some instances, toxicity equivalency factors were used to estimate the toxicity of the whole mixture; in other instances, the most toxic chemical was assumed to drive the health assessment for the whole mixture. Another approach was to treat the mixture as one entity and develop a health guidance value for the whole mixture. In yet another approach, each chemical of the mixture was evaluated separately and several health guidance values were developed. In the future, ATSDR will evaluate priority chemical mixtures found at hazardous waste sites. A weight-of-evidence approach, physiologically based pharmacokinetic modeling and bench-mark dose modeling, and quantitative structure-activity relationships will have an impact on the development of MRLs and the assessment of chemical mixtures.

Forecasting↗

Protein and cDNA structures of an acidic phospholipase A2, the enzymatic part of an unusual, two-component toxin from Vipera palaestinae.

In the venom of Vipera palaestinae an unusual, two-component toxin was found. The two components of the toxin are an acidic phospholipase A2 (VpaPLA2) and a basic protein, both with an apparent molecular mass of about 15 kDa. Each component alone is not toxic; however, their mixture is lethal. We have determined the amino acid and cDNA sequences of VpaPLA2. The protein primary structure was solved by sequencing the peptides generated by chemical cleavage of the molecule using CNBr, formic acid and hydroxylamine-hydrochloride and by enzymatic fragmentation with trypsin and chymotrypsin. VpaPLA2 consists of 122 amino acid residues and has all the structural characteristics of subgroup IIA PLA2s. It shows the highest amino acid similarity to a non-toxic phospholipase A2 from Eristocophis macmahoni (82%), whereas the most similar toxic phospholipases A2 share about 70% of residues with VpaPLA2. The substitution of His20 for a hydrophobic residue (Leu) in VpaPLA2 might be one of the reasons that its complex with the basic protein could not be observed.

Amino Acid Sequence↗

alpha-Tocopherol, ascorbic acid, and rutin inhibit synergistically the copper-promoted LDL oxidation and the cytotoxicity of oxidized LDL to cultured endothelial cells.

Low-density lipoproteins (LDL) mildly oxidized by copper ions or UV radiations exhibit a cytotoxic effect to cultured endothelial cells. Rutin, a polyphenolic flavonoid, ascorbic acid, and alpha-tocopherol were able to inhibit the peroxidation of LDL and their subsequent cytotoxicity. The mixture of the three compounds (rutin/ascorbic acid/alpha-tocopherol, 4/4/1) exhibited a supra-additive antioxidant effect. The inhibition of the cytotoxic effect was well correlated with that of TBARS formation. Another important conclusion is that these antioxidants were able to prevent directly at the cellular level the cytotoxic effect of oxidized LDL, since cells preincubated with them were protected against the cytotoxic effect of previously oxidized LDL. The protective effect of antioxidants was limited because of their own toxicity. The antioxidant mixture permitted a maximal cytoprotective effect with relatively lower concentrations to be obtained and the cytotoxicity of high concentrations to be avoided. In conclusion, rutin, ascorbic acid, and alpha-tocopherol constitute two lines of defense in protecting cells against injury owing to oxidation of LDL (1) at the LDL level, by inhibiting the LDL oxidation and the subsequent cytotoxicity, and (2) at the cellular level, by protecting the cells directly, i.e., by increasing their resistance against the cytotoxic effect of oxidized LDL.

Animals↗

Developmental toxicity study of vegetable oil-derived stanol fatty acid esters.

In a standard developmental toxicity study, a mixture of vegetable oil-derived stanol fatty acid esters was administered in the diet to groups of 28 mated female HsdCpb:WU Wistar rats at concentrations that provided 0, 1, 2.5, and 5% total stanols (equivalent to 0, 1.75, 4.38, and 8.76% plant stanol esters). Test diets were adjusted with rapeseed oil to maintain an equivalent caloric content of fatty acids at each of the treatment levels. The treatment period extended from day 0 to 21 of gestation. No compound-related toxicity or clinical effects were seen in any of the treated groups. No statistically significant differences were seen in body weights or body weight gain in the low- or mid-dose groups, although slight but statistically significant decreases in mean body weight relative to controls were seen at gestation days 7 and 14 in the high-dose group. The decreases in body weight in the high-dose group may be attributable to the virtual lack of absorption of the dietary stanols. Body weight gains were equivalent to controls throughout the study except for a statistically significant decrease seen only in the 0- to 7-day gestation period in the high-dose group. No significant effects were seen on food consumption in terms of g/rat/day, but a slight, statistically significant increase was seen in the mid-dose group during gestation days 7-14. A significant increase was seen in the high-dose group during the 7- to 21-day period of gestation. Reproductive performance was not affected by the treatment. There were no statistically significant differences in uterine weight, placental weight, fetal weight, number of fetuses, number of implantation sites, number of corpora lutea, and early/late resorptions between the treated and control groups. In addition, there was no biologically meaningful effect on fetal sex ratio. Visceral and skeletal examinations did not show any significant increases in the incidence of malformations, anomalies, or variations that were considered to be treatment related. Dietary plant (8.76% plant stanol esters) stanol esters at concentrations up to 5% total stanols were concluded to have no adverse effects on reproduction or development.

Animals↗

Use of fluidizing bed aerosol generators to establish a dust mixture of two substances at a fixed ratio for inhalation toxicity studies.

A method was developed to use two fluidizing bed generators to deliver a mixture of 1 mg cobalt + 15 mg tungsten carbide/m3 to an inhalation exposure chamber with the output from the cobalt generator split to provide the same cobalt concentration to a cobalt-only chamber. To provide a more uniform delivery of material and to minimize the amount of starting dust needed, a subsystem that produced timed bursts of compressed air was used to prevent the accumulation of dust along the aerosol transport tubes. The addition of an electrostatic precipitator placed in the exhaust lines reduced the amount of dust delivered to the high-efficiency particulate air filters, thereby reducing the number of filter changes.

Aerosols↗

Purification and characterization of two components of botulinum C2 toxin.

Two dissimilar proteins, designated as components I and II, of botulinum C2 toxin elaborated by strain 92-13 were purified to a homogeneous state. The molecular weights determined by sodium dodecyl sulfate gel electrophoresis were 55,000 for component I and 105,000 for component II. Whereas each component showed no or feeble toxicity even after being treated with trypsin, the toxicity was elicited when these two components were mixed and trypsinized. The toxicity of the mixture of components I and II at a ratio of 1:2.5 on a protein basis was 2.2 X 10(4) mouse intraperitoneal 50% lethal doses per mg of protein and increased by 2,000 times or more when treated with trypsin. These results indicate that the molecular characteristics of botulinum C2 toxin differ from those of the toxin of Clostridium botulinum types A through F in that C2 toxin is constructed with two separate protein components, which are not covalently held together, and that its toxicity is elicited by cooperation of the two components.

Botulinum Toxins↗

Dose-additive inhibition of chinook salmon acetylcholinesterase activity by mixtures of organophosphate and carbamate insecticides.

Organophosphate and carbamate insecticides are widely detected in surface waters of the western United States. These chemicals interfere with acetylcholine-mediated synaptic transmission in the nervous systems of fish and other aquatic animals via the inhibition of AChE (acetylcholinesterase) enzyme activity. Anticholinesterase insecticides commonly co-occur in the environment. This raises the possibility of antagonistic, additive, or synergistic neurotoxicity in exposed fish, including threatened and endangered species of Pacific salmon. We extracted AChE from the olfactory nervous system of chinook salmon (Oncorhynchus tshawytscha) and investigated the inhibitory effects of organophosphates (the oxon derivatives of diazinon, chlorpyrifos, and malathion) and carbamates (carbaryl and carbofuran), alone and in two-way combinations. We found that the joint toxicity of anticholinesterase mixtures can be accurately predicted from the inhibitory potencies of individual chemicals within a mixture. This indicates that organophosphate and carbamate insecticides are noninteractive in terms of AChE inhibition and that it might be possible to estimate the cumulative neurotoxicity of mixtures by simple dose addition. Because organophosphates and carbamates are likely to have additive effects on the neurobehavior of salmon under natural exposure conditions, ecological risk assessments that focus on individual anticholinesterases might underestimate the actual risk to salmon in watersheds in which mixtures of these chemicals occur.

Acetylcholinesterase↗

Molecular basis for the cross-reactivity of antibodies elicited by a natural anatoxin with alpha- and beta-toxins from the venom of Tityus serrulatus scorpion.

A non-toxic protein (TsNTxP) isolated from the venom of the noxious scorpion Tityus serrulatus (Ts) induces polyclonal antibodies cross-reactive with several toxins from the venom, in sharp contrast to anti-toxin antibodies which are toxin specific. To try to uncover the molecular basis for these unusual properties, peptide scanning experiments were performed and indicated that the N- and C-terminal parts of TsNTxP enclose continuous epitopes (residues 1-15 and 47-61). Antibodies raised against peptides corresponding to these two regions were found to have neutralizing properties against a mixture of all toxic proteins from the T. serrulatus venom, indicating that residues 1-15 and 47-61 correspond to neutralizing epitopes. The identification of key antigenic residues within these two epitopes revealed that several of them are well conserved in the amino-acid sequences of the three main toxins (Ts II, Ts IV and Ts VII) from the venom: Glu 3, Tyr 5, Asp 8, Asp 50, Trp 55 and Lys 61. A single key-residue (Glu 58) is unique to TsNTxP. By using homology modeling, a model of the three-dimensional structure of TsNTxP was obtained. The antigenically important residues from TsNTxP were found to be surface exposed, with five of them clustered on the facet of the protein reported to enclose the active site of toxins. Residues equivalent to the seven key-residues of the anatoxin were also found to be exposed in the active toxins from T. serrulatus venom. These results show that antibodies elicited by the non-toxic protein TsNTxP recognized, within the N- and C-terminal parts of toxins of T. serrulatus, conserved and surface exposed residues which might also be involved in the toxic action of the proteins.

Amino Acid Sequence↗

A comparative study of the acute inhalation toxicity of smoke from TiO2-hexachloroethane and Zn-hexachloroethane pyrotechnic mixtures.

Rats was exposed to white smoke generated from mixtures of titanium dioxide-hexachloroethane (TiO2-HC) and zinc-hexachloroethane (Zn-HC), respectively, in an inhalation chamber operated in the static mode. The dose was varied by varying the amount of smoke mixture and/or the exposure time. The acute inhalation toxicity of TiO2-HC smoke was much lower than the Zn-HC smoke. Thus, the animals survived exposure to TiO2-HC smoke, even at relatively high smoke concentrations. This smoke was irritating to the animals and minor, acute inflammatory changes were seen in lung tissue. In contrast, Zn-HC smoke was very toxic and caused lethal injuries to the experimental animals, even at relatively low concentrations. Pulmonary injuries were extensive and death was due to blood congestion with pulmonary oedema. Since the TiO2-HC and Zn-HC mixtures form TiCl4 and ZnCl2, respectively, a separate study was performed in which rats were exposed to TiCl4 gas or ZnCl2 aerosol. No animals died from exposure to TiCl4 at concentrations between 370 and 2900 mg/m3 for 10 min. The LC50 of ZnCl2 was found to be around 2000 mg/m3 during a 10-min exposure period. The difference between the two types of smoke is explained by the difference in toxicity between TiCl4 and ZnCl2.

Acute Disease↗

Eliminating toxic compounds by composting olive mill wastewater-straw mixtures.

The present work studies the changes occurring in organic matter, phenols and biotoxicity on composting olive mill wastewater with barley straw. The total organic matter decreased, a drop of 25% was reached after the stabilization phase and 52% at the end of the maturation phase. Degradation of the phenols reached 54% and 95%, respectively, after these periods. The toxicity of the water extract, evaluated by the Photobacterium phosphoreum fluorescence, decreased to disappear after only 2 months of composting. This trend was confirmed by the tight correlation between the physico-chemical and toxicity parameters, indicating that the degradation of organic matter leads to a strong reduction of the C/N ratio and of toxicity. The results obtained indicate a normal process of humification occurring during the composting of the formerly highly toxic olive mill wastewater-straw mixture and resulting in a product, which has good agricultural properties as organic fertilizer.

Fertilizers↗