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Mixture Components (mixture + component)
Selected AbstractsCumulative effects of in utero administration of mixtures of reproductive toxicants that disrupt common target tissues via diverse mechanisms of toxicityINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010C. V. Rider Summary Although risk assessments are typically conducted on a chemical-by-chemical basis, the 1996 Food Quality Protection Act required the US Environmental Protection Agency to consider cumulative risk of chemicals that act via a common mechanism of toxicity. To this end, we are conducting studies with mixtures of chemicals to elucidate mechanisms of joint action at the systemic level with the goal of providing a framework for assessing the cumulative effects of reproductive toxicants. Previous mixture studies conducted with antiandrogenic chemicals are reviewed briefly and two new studies are described. In all binary mixture studies, rats were dosed during pregnancy with chemicals, singly or in pairs, at dosage levels equivalent to approximately one-half of the ED50 for hypospadias or epididymal agenesis. The binary mixtures included androgen receptor (AR) antagonists (vinclozolin plus procymidone), phthalate esters [di(n-butyl) phthalate (DBP) plus benzyl n-butyl phthalate (BBP) and diethyl hexyl phthalate (DEHP) plus DBP], a phthalate ester plus an AR antagonist (DBP plus procymidone), a mixed mechanism androgen signalling disruptor (linuron) plus BBP, and two chemicals which disrupt epididymal differentiation through entirely different toxicity pathways: DBP (AR pathway) plus 2,3,7,8 TCDD (AhR pathway). We also conducted multi-component mixture studies combining several ,antiandrogens'. In the first study, seven chemicals (four pesticides and three phthalates) that elicit antiandrogenic effects at two different sites in the androgen signalling pathway (i.e. AR antagonist or inhibition of androgen synthesis) were combined. In the second study, three additional phthalates were added to make a 10 chemical mixture. In both the binary mixture studies and the multi-component mixture studies, chemicals that targeted male reproductive tract development displayed cumulative effects that exceeded predictions based on a response-addition model and most often were in accordance with predictions based on dose-addition models. In summary, our results indicate that compounds that act by disparate mechanisms of toxicity to disrupt the dynamic interactions among the interconnected signalling pathways in differentiating tissues produce cumulative dose-additive effects, regardless of the mechanism or mode of action of the individual mixture component. [source] Effects of metal and organophosphate mixtures on Ceriodaphnia dubia survival and reproductionENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2005Amy M. Mahar Abstract The toxicity of mixtures of copper, zinc, and diazinon were determined for Ceriodaphnia dubia using 7-d survival and reproduction tests. Fifteen treatments, including combinations of the chemicals at 0, 25, 50, 75, and 100% of their individual median lethal concentrations, adding up to one toxic unit (TU) were tested. The TU was then used to classify each mixture response as additive, greater than additive, or less than additive. For survival, additive responses occurred in the 75% zinc plus 25% diazinon and the 50% copper plus 25% zinc plus 25% diazinon treatments. For reproduction, additive responses occurred in the 75% copper plus 25% zinc, 75% copper plus 25% diazinon, and 75% zinc plus 25% diazinon treatments. Copper and zinc played a greater role in toxicity than diazinon did. Less-than-additive interactions were found in all remaining mixtures, perhaps because of differences in mode of action between diazinon and metals. Consideration of dose-response curves can help to explain inconsistencies regarding toxic response in treatments with different ratios of the same chemicals. As TU percentages changed, mixture components were taken from different locations on differently shaped dose-response curves. Because most responses were less than additive, however, water-quality criteria based on individual concentrations probably are protective for most metal-organophosphate mixtures. [source] Algal toxicity of nitrobenzenes: Combined effect analysis as a pharmacological probe for similar modes of interactionENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2005Rolf Altenburger Abstract An analysis regarding the effects of the mixture toxicity of different nitrobenzenes on the reproduction of the green alga Scenedesmus vacuolatus was undertaken using the concepts of concentration addition and response addition. Using lipophilicity-based quantitative structure-activity relationship (QSAR) modeling for nitrobenzenes, the assumption is held that mononitrobenzenes may exert narcotic effects as a common type of action, whereas dinitrobenzenes show a somewhat greater toxicity. From the literature, QSARs based on quantum chemical parameters suggest that some mononitrobenzenes may be effective through additional other modes of action. The toxicity of a mixture of 14 nitrobenzenes clearly exceeds the predicted combined effects, as expected for the sum of toxic units from a uniform narcotic mode of action. Moreover, the observed combined effect is smaller than that predicted from similarly acting compounds calculated on the basis of the parameterized dose-response functions using concentration addition. Further modeling of the combined effect, joining the models of concentration addition for components with anticipated similar modes of action and of response addition for those with independent action, led us to propose that not all nitrobenzenes follow the same mode of action. This idea is in line with the hypothesis derived from quantum chemical QSAR considerations. Most interestingly, the methodology introduced here uses combined effect analysis as a pharmacological probe to test for similarity in the mode of action of mixture components. [source] Bauxite manufacturing residues from Gardanne (France) and Portovesme (Italy) exert different patterns of pollution and toxicity to sea urchin embryosENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2002Giovanni Pagano Abstract This study was designed to investigate the composition and toxicity of solid residues from bauxite manufacturing plants. Soil and dust samples were collected in the proximity of two bauxite plants (Gardanne, France, and Portovesme, Italy). Samples were analyzed for their content of some selected inorganic contaminants by means of inductively coupled plasma optical emission spectroscopy (ICP-OES) either following acid digestion procedures or by seawater release of soluble components. Toxicity was tested by sea urchin bioassays to evaluate a set of toxicity endpoints including acute embryotoxicity, developmental defects, changes in sperm fertilization success, transmissible damage from sperm to the offspring, and cytogenetic abnormalities. Inorganic analysis showed two distinct sets of inorganic contaminants in Gardanne versus Portovesme, including Al, Cr, Cu, Fe, Mn, Pb, Ti, and Zn; sample composition (seawater-soluble cotaminants) and toxicity showed a noteworthy association. The most severe toxicity to embryogenesis and to sperm fertilization success was exerted by some Portovesme samples (0.03,0.5% w/v), with a significant association between toxicity and dose-related seawater release of Zn, Pb, and Mn. Seawater extraction of a toxic dust sample (G20) from the Gardanne factory showed increasing seawater release of Al, Fe, and Mn; the G20 sample, at the level of 0.5%, affected both developing sea urchin embryos and sperm (offspring quality). Soil samples around the Gardanne factory showed the highest frequency of toxic soil sites eastward from the factory. The present data point to solid deposition from bauxite plants as a potential subject of environmental health concern. The results suggest that extraction methods for evaluating the toxicity of complex mixtures should be based on the environmental availability of mixture components. The differences in sample toxicity among the tested sites, however, suggest possible site-to-site variability in geochemical and/or technological parameters. [source] Interactive curve resolution by using latent projections in polar coordinatesJOURNAL OF CHEMOMETRICS, Issue 1-2 2007J. von Frese Abstract The problem of resolving bilinear two-way data into the contributions from the underlying mixture components is of great interest for all hyphenated analytical techniques. The fact that the optimal solution to this problem at least to some extent depends on the nature of the data under study has lead to a numerous different approaches. One of the seminal publications in this area was contributed by Olav M. Kvalheim and Yi-Zeng Liang in 1992. They not only provided valuable Heuristic Evolving Latent Projections (HELP) but also enlightened many important aspects of curve resolution in this and numerous subsequent publications. Here we extend their key concept of HELP, that is the use of latent projective graphs for identifying one-component regions, by using polar coordinates for these analyses and thereby creating a simple, intuitive exploratory tool for directly solving the curve resolution problem for two and three components graphically. Our approach is demonstrated with simulated data, an example from reaction monitoring with broadband ultrafast spectroscopy and one chemometric standard data set. Copyright © 2007 John Wiley & Sons, Ltd. [source] Preparative separation of a multicomponent peptide mixture by mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 2 2006Xinli Yang Abstract We report on the first multiplex preparative separation by mass spectrometry of bio-organic molecules in the 200,350 Da mass range that is typical for synthetic drugs. A five-component mixture consisting of two di- and three tripeptides has been separated by mass using a specially designed mass spectrometer. The instrument for preparative separations consists of an electrospray ionization (ESI) source, ion transfer optics, an electrostatic sector, and an inhomogeneous-field magnetic mass analyzer that achieves linear mass dispersion of ion beams. Protonated peptides produced by electrospray were separated, nondestructively landed on a 16-channel array of dry collector plates, and reconstituted in solution. The preparation procedures and the instrumental conditions have been optimized to maximize the ion currents. The significant features of the special mass spectrometer are high ion currents and simultaneous separation and collection of mixture components. Copyright © 2006 John Wiley & Sons, Ltd. [source] Hybrid Dirichlet mixture models for functional dataJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 4 2009Sonia Petrone Summary., In functional data analysis, curves or surfaces are observed, up to measurement error, at a finite set of locations, for, say, a sample of n individuals. Often, the curves are homogeneous, except perhaps for individual-specific regions that provide heterogeneous behaviour (e.g. ,damaged' areas of irregular shape on an otherwise smooth surface). Motivated by applications with functional data of this nature, we propose a Bayesian mixture model, with the aim of dimension reduction, by representing the sample of n curves through a smaller set of canonical curves. We propose a novel prior on the space of probability measures for a random curve which extends the popular Dirichlet priors by allowing local clustering: non-homogeneous portions of a curve can be allocated to different clusters and the n individual curves can be represented as recombinations (hybrids) of a few canonical curves. More precisely, the prior proposed envisions a conceptual hidden factor with k -levels that acts locally on each curve. We discuss several models incorporating this prior and illustrate its performance with simulated and real data sets. We examine theoretical properties of the proposed finite hybrid Dirichlet mixtures, specifically, their behaviour as the number of the mixture components goes to , and their connection with Dirichlet process mixtures. [source] Web server suite for complex mixture analysis by covariance NMRMAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2009Fengli Zhang Abstract Elucidation of the chemical composition of biological samples is a main focus of systems biology and metabolomics. Their comprehensive study requires reliable, efficient, and automatable methods to identify and quantify the underlying metabolites. Because nuclear magnetic resonance (NMR) spectroscopy is a rich source of molecular information, it has a unique potential for this task. Here we present a suite of public web servers (http://spinportal.magnet.fsu.edu), termed COLMAR, which facilitates complex mixture analysis by NMR. The COLMAR web portal presently consists of three servers: COLMAR covariance calculates the covariance NMR spectrum from an NMR input dataset, such as a TOCSY spectrum; COLMAR DemixC method decomposes the 2D covariance TOCSY spectrum into a reduced set of nonredundant 1D cross sections or traces, which belong to individual mixture components; and COLMAR query screens the traces against a NMR spectral database to identify individual compounds. Examples are presented that illustrate the utility of this web server suite for complex mixture analysis. Copyright © 2009 John Wiley & Sons, Ltd. [source] The design of an on-line semi-preparative LC,SPE,NMR system for trace analysis,MAGNETIC RESONANCE IN CHEMISTRY, Issue 9 2005Feng Xu Abstract This paper reports the design of an on-line semi-preparative LC,SPE,NMR system and its use in the structural analysis of mixture components at the 0.02,1% level. The combination provides at least a five fold mass sensitivity increase over that obtained from typical analytical LC,SPE systems and a >30-fold total NMR sensitivity enhancement over analysis by LC,NMR. This is accomplished by using a novel on-line device to store, dilute (1,100-fold) and deliver (at an optimized flow-rate) the isolated component of interest to an SPE trap unit. The SPE unit consists of two cartridges connected in parallel to increase the overall SPE capacity and also to decrease the flow-rate through each trap for enhanced trapping efficiency. As the coupling of semi-preparative LC with NMR (through SPE) is well matched in terms of optimal mass loading for both techniques, only one LC,SPE cycle is required to enrich a 50 µg ml,1 component (1% in a 5 mg ml,1 mixture) for the acquisition of heteronuclear 1H,13C NMR data using a conventional NMR flow probe. Furthermore, analytes at the 0.02% level (,1 µg ml,1) can be studied using 2D 1H NMR techniques if peak cuts from replicate sample injections (,3) are accumulated into the storage/dilution unit and the resulting solution processed by just one SPE trap and elute cycle. Copyright © 2005 John Wiley & Sons, Ltd. [source] Mixture and mixture,process variable experiments for pharmaceutical applicationsPHARMACEUTICAL STATISTICS: THE JOURNAL OF APPLIED STATISTICS IN THE PHARMACEUTICAL INDUSTRY, Issue 4 2004Christine M. Anderson-Cook Abstract Many experiments in research and development in the pharmaceutical industry involve mixture components. These are experiments in which the experimental factors are the ingredients of a mixture and the response variable is a function of the relative proportion of each ingredient, not its absolute amount. Thus the mixture ingredients cannot be varied independently. A common variation of the mixture experiment occurs when there are also one or more process factors that can be varied independently of each other and of the mixture components, leading to a mixture,process variable experiment. We discuss the design and analysis of these types of experiments, using tablet formulation as an example. Our objective is to encourage greater utilization of these techniques in pharmaceutical research and development. Copyright © 2004 John Wiley & Sons Ltd. [source] Liquid chromatography ion trap mass spectrometric analysis of oligosaccharides using permethylated derivativesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 5 2001Jeannine Delaney Reversed phase liquid chromatography was combined with the multiple stage mass analysis capability of an ion trap mass spectrometer for the characterization of permethylated oligosaccharide mixtures. The new method was used to separate the components of an unlabeled permethylated maltooligomer ladder, a 2-aminobenzamide-labeled (2-AB) maltooligomer ladder, a complex mixture of 2AB-labeled bi- (B), tri- (T), and tetraantennary (Q) standards, and a mixture of recombinant glycoprotein carbohydrates from soluble CD4 with varying sialic acid (S) content. Using reversed phase HPLC, permethylated mixture components including , and , anomers were separated based on their structures. Fluorescent labeling with 2-aminobenzamide prior to permethylation was employed for off-line method development, but was not necessarily required for mass spectral analysis, as permethylation alone improved the ionization and fragmentation characteristics of the molecules. Antennae composition of permethylated derivatives was determined in MS2 where the fragmentation patterns of the Y- and B-ion series predominated, and then further evaluated in MS3, which provided additional information on branching obtained from A and X cross-ring fragmentation. Copyright © 2001 John Wiley & Sons, Ltd. [source] ESTIMATING COMPONENTS IN FINITE MIXTURES AND HIDDEN MARKOV MODELSAUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS, Issue 3 2005D.S. Poskitt Summary When the unobservable Markov chain in a hidden Markov model is stationary the marginal distribution of the observations is a finite mixture with the number of terms equal to the number of the states of the Markov chain. This suggests the number of states of the unobservable Markov chain can be estimated by determining the number of mixture components in the marginal distribution. This paper presents new methods for estimating the number of states in a hidden Markov model, and coincidentally the unknown number of components in a finite mixture, based on penalized quasi-likelihood and generalized quasi-likelihood ratio methods constructed from the marginal distribution. The procedures advocated are simple to calculate, and results obtained in empirical applications indicate that they are as effective as current available methods based on the full likelihood. Under fairly general regularity conditions, the methods proposed generate strongly consistent estimates of the unknown number of states or components. [source] | |||||||||||||