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Results for “Mixture effects”

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PubMed2004

Toxicity of binary mixtures of cadmium-copper and carbendazim-copper to the nematode Caenorhabditis elegans.

For ecological risk assessment, the additive model may be used to empirically predict toxic mixture effects. Detailed toxicity tests were performed to determine whether effects of mixtures of copper-cadmium and copper-carbendazim on Caenorhabditis elegans were similar to the effects of the individual compounds. Effects on the course of reproduction, the length of the juvenile period, the length of the reproductive period, and body length were analyzed. Dose-response data were compared to the additive model and tested for four deviation patterns from additivity: No deviation, synergistic/antagonistic deviation, dose ratio-dependent deviation, dose level-dependent deviation. During the exposure, the cadmium-copper effect on reproduction changed from a synergistic, to a dose ratio-dependent deviation from additivity. More cadmium in the mixture decreased the toxicity and more copper increased the toxicity. The effect of copper-carbendazim on reproduction was synergistic at low dose levels and antagonistic at high dose levels and independent of time. Mixture effects on the juvenile and reproductive period were similar to single component effects. It was concluded that the observed time-dependence of toxic interactions was small and that interactions on the timing of reproduction were not found. The additive model underestimated mixture effects on reproduction and body length.

Animals↗

PubMed2006

Effect of pressure on molecular and ionic motions in ultraviscous acetaminophen-aspirin mixture.

Effect of pressure and temperature on molecular motions and dc conductivity in ultraviscous, 50 wt% acetaminophen-aspirin melt has been studied by dielectric relaxation spectroscopy. The spectra obtained over the pressure range, 5-300 MPa and temperature range, 295-320 K show a distribution of relaxation times greater than found in pure acetaminophen. The equilibrium dielectric permittivity and relaxation time, tau, of the melt increase with increase in pressure and decrease in temperature and the dc conductivity, sigma(dc), decreases. The pressure and temperature variation of the limiting high frequency permittivity shows significant contribution from infrared polarization. The volumes of activation for sigma(dc) and tau vary with both the pressure and temperature, indicating that there is also a structural effect that determine sigma(dc). This effect would add a non-linear term to the Debye-Stokes-Einstein equation for variation of sigma(dc) with tau. The ultraviscous liquid remains stable with time, and with change in temperature and pressure, suggesting that a more stable glassy state of a pharmaceutical may be obtained by mixing a second component.

Acetaminophen↗

PubMed2003

Effects of mixtures of lauric and myristic acid on rumen methanogens and methanogenesis in vitro.

AIMS: To identify the most effective mixture of non-esterified lauric (C12) and myristic (C14) acid in suppressing ruminal methanogenesis, and to investigate their effects on the methanogenic population. METHODS AND RESULTS: C12/C14 mixtures were incubated with rumen fluid using the Hohenheim gas test apparatus. Methane production and the numbers of Archaea declined with an increasing proportion of C12. With a 2 : 1 proportion of C12/C14, the maximum methane-suppressing effect (96%) was achieved similar to that with C12 alone. The proportions of the individual methanogenic orders of total methanogens were altered by varying the C12/C14 ratio. CONCLUSIONS: Although C14 alone had no effect on methanogenesis, C14 enhanced the methane-suppressing effect of C12 in certain mixtures. SIGNIFICANCE AND IMPACT OF THE STUDY: The results support strategies for an environment-friendly ruminant nutrition as it was demonstrated that part of the less palatable C12 could be replaced by C14 without losing its methane-suppressing potential.

Animals↗

PubMed2005

Different types of combination effects for the induction of micronuclei in mouse lymphoma cells by binary mixtures of the genotoxic agents MMS, MNU, and genistein.

Distinction between dose addition and response addition for the analysis of the toxicity of mixtures may allow differentiation of the components regarding similar versus independent mode of action. For nonlinear dose responses for the components, curves of dose addition and response addition differ and embrace an "envelope of additivity." Synergistic or antagonistic interaction may then be postulated only if the mixture effect is outside this surface. This situation was analyzed for the induction of micronuclei in L5178Y mouse lymphoma cells by the two methylating agents methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (MNU) and the topoisomerase-II inhibitor genistein (GEN). All three chemicals reproducibly generated sublinear (upward convex) dose-response relationships. For the analysis of mixture effects, these genotoxic agents were investigated in the three binary combinations. Statistical testing for dose addition along parallel exponential dose responses was performed by linear regression with interaction based on the logarithm of the number of cells that contain micronuclei. For MMS+MNU, the mixture effect was compatible with dose addition (i.e., significantly larger than calculated for the addition of net responses). For MMS+GEN, the measured effect was larger than for response addition but smaller than for dose addition. For MNU+GEN, the measured effect was below response addition, indicative of true antagonism. In the absence of knowledge on the sublinear dose-response relationships for the individual components, a synergistic effect of MMS on both MNU and GEN would have been postulated erroneously. The observed difference between MMS and MNU when combined with GEN would not have been predicted on the basis of a simplistic interpretation of DNA methylation as the mode of action and may be due to differences in the profile of DNA methylations and/or epigenetic effects. We conclude that knowledge of nonlinearities of the dose-response curves of individual components of a mixture can be crucial to analyze for synergism or antagonism and that an in-depth mechanistic knowledge is useful for a prediction of similarity or independence of action.

Alkylating Agents↗

PubMed2005

Effect of biogenic substrate concentration on the performance of sequencing batch reactor treating 4-CP and 2,4-DCP mixtures.

Effect of a biogenic substrate (peptone) concentration on the performance of sequencing batch reactor (SBR) treating 220 mg/l 4-chlorophenol (4-CP) and 110 mg/l 2,4-dichlorophenol (2,4-DCP) mixtures was investigated. In this context, peptone concentration was gradually decreased from 300 mg/l to null in which chlorophenols were fed to the reactor as sole carbon and energy sources. By this way, the effect of peptone concentration on observed yield coefficient (Y), biomass concentration, chlorophenols and COD removal performances were investigated. Decreasing peptone concentration accompanied with lower biomass concentration led to increase in peak chlorophenol and COD concentrations within the reactor during each SBR cycle. This, in turn, caused noteworthy declines in the removal rates as chlorophenol degradations followed Haldane substrate inhibition model. Also, increased peak chlorophenol concentrations led to the accumulation of 5-chloro-2-hydroxymuconic semialdehyde (CHMS), which is -meta cleavage product of 4-CP. Despite the decreased removal rates, complete chlorophenols and CHMS degradation, in addition to high COD removal efficiencies (>90%), were observed for all studied conditions, even chlorophenols were added as sole carbon and energy sources. Another significant point is that 2,4-DCP at slightly elevated concentrations (>20 mg/l) within the reactor caused a strong competitive inhibition on 4-CP degradation. In SBR, feeding the influent to the reactor within a certain period (i.e. filling period) provided dilution of coming wastewater, which decreased the chlorophenols concentrations to which microorganisms were exposed. Therefore, use of SBR may help to avoid both self and competitive inhibitions in the treatment of 4-CP and 2,4-DCP mixture especially in the presence high biogenic substrate concentrations. In addition, isolation and identification studies have indicated that Pseudomonas sp. and Pseudomonas stutzeri were dominant species in the acclimated mixed culture.

Biodegradation, Environmental↗

PubMed1998

[The acid-base status of preserved blood before and after processing with an oxygen-ozone mixture].

Effects were studied of oxygen and ozone mixture on the indices for the contained donor blood acid-base state. Ozonation of blood in 9 donors was carried out in different concentrations of ozone in the oxygen and ozone mixture. Revealed in blood after ozonation was increase in oxygen concentration and decrease in CO2 dissoluble fraction, with pH of blood, the content of bicarbonate being unchanged. There was no relatedness of the ozonized blood saturation with oxygen to the concentration of ozone in the oxygen and ozone mixture.

Acid-Base Equilibrium↗

PubMed2001

Mixture component effects on the in vitro dermal absorption of pentachlorophenol.

Interactions between chemicals in a mixture and interactions of mixture components with the skin can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous disposition of a topically applied chemical. The predictive ability of dermal absorption models, and consequently the dermal risk assessment process, would be greatly improved by the elucidation and characterization of these interactions. Pentachlorophenol (PCP), a compound known to penetrate the skin readily, was used as a marker compound to examine mixture component effects using in vitro porcine skin models. PCP was administered in ethanol or in a 40% ethanol/60% water mixture or a 40% ethanol/60% water mixture containing either the rubefacient methyl nicotinate (MNA) or the surfactant sodium lauryl sulfate (SLS), or both MNA and SLS. Experiments were also conducted with 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB). Maximal PCP absorption was 14.12% of the applied dose from the mixture containing SLS, MNA, ethanol and water. However, when PCP was administered in ethanol only, absorption was only 1.12% of the applied dose. There were also qualitative differences among the absorption profiles for the different PCP mixtures. In contrast with the PCP results, absorption of TCB or PCB was negligible in perfused porcine skin, with only 0.14% of the applied TCB dose and 0.05% of the applied PCB dose being maximally absorbed. The low absorption levels for the PCB congeners precluded the identification of mixture component effects. These results suggest that dermal absorption estimates from a single chemical exposure may not reflect absorption seen after exposure as a chemical mixture and that absorption of both TCB and PCB are minimal in this model system.

Administration, Topical↗

PubMed1998

Lack of suppressive effects of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDS), polychlorinated dibenzofurans (PCDFS), and aroclor biphenyls (PCBS) on mixed lymphocyte reaction, phagocytic, and natural killer cell activities of rat leukocytes in vitro.

Rat splenocyte mixed leukocyte reaction (MLR), splenic natural killer (NK) cell activity, and phagocytic activities of splenic, peritoneal, and peripheral blood leukocytes (PBLs) were evaluated in vitro to determine the immunotoxicity of mixtures containing low levels of methylmercury (MeHg), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and Aroclor polychlorinated biphenyls (PCBs). The mixtures were based on the concentrations of the chemicals in fish flesh. Leukocytes from male Fischer rats were exposed to MeHg (0.1-2 microg/ml), PCDD/PCDF mixtures (1-15 pg/ml) of three PCDDs (2,3,7,8-tetrachlorodibenzo-p-dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin, and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin) and two PCDFs (2,3,7,8-tetrachlorodibenzofuran and 1,2,3,7,8-pentachlorodibenzofuran), three Aroclor PCB (Aroclor 1242, 1254, and 1260) mixtures (0.01-0.5 microg/ml), or combinations of MeHg/PCB/PCDD/PCDF mixtures for 24 or 72 h before immunological assays. Phagocytosis and NK cell cytotoxicity were evaluated with a flow cytometer, and MLR of Fischer rat responder splenocytes cultured with mitomycin C-treated Long-Evans splenocytes by [3H]thymidine uptake. Exposure to MeHg (2 microg/ml) alone or with PCB/ PCDD/PCDF resulted in significant cytolethality in rat splenocytes, peritoneal leukocytes, and PBLs at 24 h exposure. Treatment with Aroclor PCB mixtures, PCDD/PCDF mixtures, 0.1 microg MeHg/ml (noncytolethal), or PCB/PCDD/PCDF mixtures with 0.1 microg MeHg/ml caused no suppression of splenocyte MLR response, splenic NK cell-mediated lysis of Yac-l cells, or phagocytosis of fluorescent beads by splenic, peritoneal, and peripheral blood phagocytic cells. The results indicate that in vitro exposure of rat leukocytes to low levels of MeHg, Aroclor PCB mixtures, PCDD/PCDF mixtures, or MeHg/PCB/PCDD/PCDF mixtures had no suppressive effects on the immune functions assayed, and thus produced no additive immunotoxicity. However, in order to predict the potential risk of these chemical mixtures to the human immune system, in vivo animal studies with blood (tissue) levels compatible with the levels of MeHg, PCBs, and PCDDs/PCDFs in exposed human populations should be evaluated.

Animals↗

PubMed2007

The mirror effect and mixture signal detection theory.

The mirror effect for word frequency refers to the finding that low-frequency words have higher hit rates and lower false alarm rates than high-frequency words. This result is typically interpreted in terms of conventional signal detection theory (SDT), in which case it indicates that the order of the underlying old item distributions mirrors the order of the new item distributions. However, when viewed in terms of a mixture version of SDT, the order of hits and false alarms does not necessarily imply the same order in the underlying distributions because of possible effects of mixing. A reversal in underlying distributions did not appear for fits of mixture SDT models to data from 4 experiments.

Attention↗

PubMed1981

Additive and non-additive effects of mixtures of short-acting intravenous anaesthetic agents and their significance for theories of anaesthesia.

1 The potency of a series of short-acting anaesthetics was established by measuring the duration of the loss of righting reflex following a single bolus injection into the tail vein of male Wistar rats. The agents were, in order of potency, etomidate, alphaxalone, methohexitone, alphadalone acetate and propanidid.2 The potency of binary mixtures of these agents was also assessed to see whether the anaesthetic effects of different agents were additive as classical theories of anaesthesia suggest. Mixtures of alphaxalone and alphadalone acetate, alphaxalone and propanidid and methohexitone and propanidid all showed simple additive effects. Mixtures of alphaxalone and etomidate and of alphaxalone and methohexitone showed a greater potency than would be expected if their effects were simply additive. Mixtures of etomidate and methohexitone were not examined.3 Mixtures of alphaxalone and either methohexitone or pentobarbitone produced a greater depression of synaptic transmission in in vitro preparations of guinea-pig olfactory cortex than would have been expected from the sum of the activities of the individual anaesthetics. Other combinations of anaesthetics did not show similar effects although the interaction between alphaxalone and etomidate was not examined.4 Neither alphaxalone nor pentobarbitone affected the membrane: buffer partition coefficient of the other for a model membrane system.5 These results are interpreted as evidence against the classical unitary hypotheses of anaesthetic action based on correlations of anaesthetic potency with lipid solubility and as supporting the view that different anaesthetics act on different structures in the neuronal membranes to produce anaesthesia.

Anesthesia, Intravenous↗

PubMed2006

Modeling effects of mixtures of endocrine disrupting chemicals at the river catchment scale.

For endocrine disrupting chemicals in the environment, concerns arise primarily from the effects that may be induced in wildlife. A well studied example is estrogenic chemicals in the aquatic environment and their effects on fish. Directly measuring effects, in fieldwork studies, is an expensive and time-consuming approach that is fraught with many difficulties, ranging from study design right through to data analysis and interpretation. An alternative approach would be to predict the scale of effect(s) using suitable modeling techniques. We have attempted to do this using estrogenic chemicals as an example. We chose this group of aquatic pollutants because of the current considerable interest in them and the wealth of biological data available on them. Using the established GREAT-ER hydrological model,we have first predicted the concentrations and then the estrogenic effects on fish, of estrone, estradiol, ethinyl estradiol, and nonylphenol individually throughout an entire river catchment. We then show that knowledge of the biological responses of fish to mixtures of these chemicals can be used to predict the effect of environmentally realistic mixtures of them. To determine the degree of risk posed by this group of chemicals, it was necessary to take into account mixture effects: assessment on a chemical by chemical basis led to underestimations of the risk. Finally, we show that the approach can be used to predict how the risk will be affected by changes in the concentration of one chemical in the mixture. Although we have used only one endpoint (vitellogenin induction as an estrogenic response) and one group of similarly acting chemicals, we suggest that this general approach could prove extremely useful to regulatory authorities and other parties charged with protecting aquatic wildlife from adverse effects caused by chemicals in their environment.

Endocrine Disruptors↗

PubMed1994

Hypocholesterolemic effects of mixture Da Huai on experimental rats and treatment of a homozygous FH child.

This study observes the hypocholesterolemic effects of Mixture Da Huai--a drug of enhancing monocyte macrophage system--on experimental rats, and the treatment of a homozygous familial hypercholesterolemia (FH) child. The results show that TC, VLDL-C and LDL-C in Mixture Da Huai group were significantly reduced and HDL-C was significantly increased. Fractional clearance rates for 125I-GLC-LDL, and the 125I-GLD-LDL uptake of rat peritoneal macrophages were significantly increased. Excretions of total sterol and acidic sterol in feces were also increased. After treatment for 3 months, serum TC and LDL-C of a homozygous FH child were significantly decreased. Tendon and cutaneous xanthomas were limited. This study indicates that by promoting the monocyte macrophage system to degrade LDL, a promising prevention and treatment of hypercholesterolemia and atherosclerosis might be provided, especially in the treatment of homozygous FH.

Animals↗

PubMed2003

Mass spectrometric analysis of DNA mixtures: instrumental effects responsible for decreased sensitivity with increasing mass.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has demonstrated great potential to replace gel electrophoresis for DNA sequence analysis. A current limitation in this method is, however, the decreased sensitivity with increasing mass of DNA molecules. In the present study, instrumental effects on the mass analysis of DNA molecules were investigated quantitatively using an equimolar DNA mixture. It is shown that detection efficiency, detector saturation, and ion beam divergence account for the entirety of the observed falloff in signal intensity with increasing mass. Although the present study focused upon the analysis of DNA mixtures, the instrumental effects observed apply equally to other macromolecular mixtures (e.g., proteins, polymers).

Algorithms↗

PubMed1978

A new model for health effects of air pollutants: evidence for synergistic effects of mixtures of ozone and sulfuric acid aerosols on rat lungs.

Chronic respiratory disease-free rats were exposed to relatively low levels of ozone (0.4 to 0.5 ppm) and H2SO4 aerosols (11 to 3,000 microgram/m3) and to mixtures of these pollutants. We independently evaluated exposure effects on conducting airway metabolism as rate of secretion of mucus glycoproteins by tracheal explants and on lung homogenates (predominantly lung parenchyma) by various chemical assays. True synergism was observed in that the response to the mixture of gases exceeded the sum of effects observed with the same concentration of either gas alone. Wet to dry weight ratios; DNA, protein, and RNA content; and the activities various lysosomal hydrolases in the lung homogenate all increased upon exposure to O3-H2-SO4 mixtures concomitant with observed increases in the rate of secretion of mucus glycoproteins by tracheal explants from the same rats. Preliminary experiments suggest that all of these effects are reversible when rats are allowed to recover after exposure. We conclude that the lack of toxicity noted upon exposure of experimental animals to individual pollutant gases at near-ambient levels should be interpreted with caution, since there is now epidemiological, physiological, and biochemical evidence that mixtures of pollutant gases may show synergistic effects.

Aerosols↗

PubMedDate not supplied

Differential effects of mixtures of cholesterol oxidation products on bovine aortic endothelial cells and human monocytic U937 cells.

Cholesterol oxidation products or oxysterols are of interest due to their hypothesized role in the development of atherosclerosis. The objective of the present study was to assess the cytotoxic effects of mixtures of oxysterols: 25-hydroxycholesterol (25-OHC), 7beta-hydroxycholesterol (7beta -OHC), and cholesterol-5beta,6beta -epoxide (beta -epox) on two cell types associated with the atherosclerotic process, bovine aortic endothelial (BAE) cells and human monocytic U937 cells. Cells were exposed to 25-OHC, 7beta -OHC, or beta -epox, or equimolar mixtures (30 mu M) of 25-OHC and 7beta -OHC, 25-OHC and beta-epox, or 7beta-OHC and beta -epox for 48 h. Cell viability was assessed using the fluorescein diacetate/ethidium bromide (FDA/ EtBr) assay and nuclear morphology following staining with Hoechst 33342. 25-OHC was the least toxic of the oxysterols and did not induce apoptosis in either cell line. Both 7beta-OHC and beta -epox treatments were cytotoxic and induced apoptosis in the cells. Cotreatment with 25-OHC did not alter the toxicity of 7beta -OHC and beta -epox in U937 cells but did decrease the percentage apoptotic cell death. In contrast, in the BAE cells cotreatment with 25-OHC had a slight protective effect on 7beta -OHC and beta-epox-induced toxicities and a marked decrease in apoptotic cell death. The 7beta -OHC and beta -epox mixture induced a significant increase in apoptotic cell death in U937 cells but decreased this mode of cell death in the BAE cells. The effects of oxysterols on glutathione levels also differed between the cells with changes noted in U937 and not in BAE cells. Results demonstrate interactive effects when oxysterols are studied as mixtures rather than single compounds in vitro.

Animals↗

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↗

PubMed1992

Effect of mixture of surfactants and adsorbents on anaerobic digestion of water hyacinth-cattle dung.

In an effort to improve the anaerobic digestion of water hyacinth-cattle dung with enriched methane content, the effects of mixtures of surfactant-surfactant, adsorbent-adsorbent and surfactant-adsorbent have been studied in various combinations. Among the combinations tested, bentonite and gelatin, gelatin and Tegoprens 43, sodium lauryl sulfate and Tegoprens 42, and Tegoprens 47 and Tegoprens 63 showed more than a 100% increase in gas production with higher methane yield.

Adsorption↗

PubMed2004

Metabolic effects of mixture containing branched-chain amino acids and taurine during subchronic poisoning with barbiturates.

We studied the effect of a mixture containing branched-chain amino acids and taurine on the pool of free amino acids and their derivatives during chronic phenobarbital poisoning. Subchronic barbiturate poisoning produced by daily intraperitoneal injection of phenobarbital caused imbalance in the content of some amino acids in blood plasma and liver of rats. Treatment with the mixture of branched-chain amino acids and taurine normalized the content of amino acids in the liver and blood plasma of animals with subchronic phenobarbital poisoning. The mixture of branched-chain amino acids and taurine corrects metabolic processes and normalized the peripheral pool of amino acids. Our findings extend the range for application of amino acids in clinical practice.

Amino Acids↗