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    Effect of vehicles and sodium lauryl sulphate on xenobiotic permeability and stratum corneum partitioning in porcine skin

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    Dermal contact with potentially toxic agricultural and industrial chemicals is a common hazard encountered in occupational, accidental spill and environmental contamination scenarios. Different solvents and chemical mixtures may influence dermal absorption. The effects of sodium lauryl sulphate (SLS) on the stratum corneum partitioning and permeability in porcine skin of 10 agricultural and industrial chemicals in water, ethanol and propylene glycol were investigated. The chemicals were phenol, p-nitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. SLS decreased partitioning into stratum corneum from water for lipophilic compounds, decreased partitioning from propylene glycol and did not alter partitioning from ethanol. SLS effects on permeability were less consistent, but generally decreased permeability from water, increased permeability from ethanol and had an inconsistent effect on permeability from propylene glycol. It was concluded that, for the compounds tested, partitioning into the stratum corneum was determined by the relative solubility of the solute in the donor solvent and the stratum corneum lipids. Permeability, however, reflected the result of successive, complex processes and was not predictable from stratum corneum partitioning alone. Addition of SLS to solvents altered partitioning and absorption characteristics across a range of compounds, which indicates that partition coefficients or skin permeability from neat chemical exposure should be used with caution in risk assessment procedures for chemical mixtures

    Cluster analysis of the dermal permeability and stratum corneum/solvent partitioning of ten chemicals in twenty-four chemical mixtures in porcine skin

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    Assumptions based on absorption from single solvent systems may be inappropriate for risk assessment when chemical mixtures are involved. We used K-means and hierarchical cluster analyses to identify clusters in stratum corneum partitioning and porcine skin permeability datasets that are distinct from each other based on mathematical indices of similarity and dissimilarity. Twenty four solvent systems consisting of combinations of water, ethanol, propylene glycol, methyl nicotinate and sodium lauryl sulphate were used with 10 solutes, including phenol, pnitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. Identifying the relationships between solvent systems that have similar effects on dermal absorption formed the bases for hypotheses generation. The determining influence of solvent polarity on the partitioning data structure supported the hypothesis that solvent polarity drives the partitioning of non-polar solutes. Solvent polarity could not be used to predict permeability because solvent effects on diffusivity masked the effects of partitioning on permeability. The consistent influence of the inclusion of propylene glycol in the solvent system supports the hypothesis that over saturation due to solvent evaporation has a marked effect on permeability. These results demonstrated the potential of using cluster analysis of large datasets to identify consistent solvent and chemical mixture effects

    Comparative studies on the effects of water, ethanol and water/ethanol mixtures on chemical partitioning into porcine stratum corneum and silastic membrane

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    The effects of water and ethanol vehicles on stratum corneum and silastic membrane partitioning of 11 industrial and agricultural compounds were studied to aid in characterizing and assessing risk from skin exposure. Zero percent, 50% and 100% aqueous ethanol solutions were used as solvents for 14C labeled phenol, 4-nitrophenol, pentachlorophenol, dimethyl parathion, parathion, chloropyrifos, fenthion, triazine, atrazine, simazine and propazine. Compound partitioning between the solvents and porcine stratum corneum/silastic membrane were estimated. Stratum corneum was exposed to aqueous ethanol ranging from 0% to 100% v/v ethanol in 20% increments and Fourier transform infrared spectroscopy (FT-IR) was used to obtain an index of lipid disorder. Gravimetry and FT-IR were used to demonstrate lipid extraction in aqueous ethanol solutions. Partitioning patterns in silastic membranes resembled those in stratum corneum and were correlated with octanol/water partitioning. Partitioning was highest in water and was higher from 50% ethanol than from 100% ethanol, except for parathion, 4-nitrophenol, atrazine and propazine. Correlation existed between molecular weight and partitioning in water, but not in ethanol and ethanol/water mixtures. Lipid order, as reflected in FTIR spectra, was not altered. These studies suggest that stratum corneum partitioning of the compounds tested is primarily determined by relative compound solubility between the stratum corneum lipids and the donor solvent. Linear relationships existed between octanol/water partitioning and stratum corneum partitioning. Partitioning was also correlated with molecular weight in water solvent systems, but not in ethanol and ethanol/water mixtures. Ethanol and ethanol/water mixtures altered the stratum corneum through lipid extraction, rather than through disruption of lipid order

    The Dermal Absorption of Selected Agricultural and Industrial Chemicals Through Porcine Skin with Emphasis on Chemical Mixture Effects

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    The stratum corneum is the primary barrier to dermal absorption and the processes of absorption include partitioning into, and diffusion through, the lipid matrix of the stratum corneum. These studies were aimed at furthering our understanding of these processes and modeling dermal absorption. We used 11 industrial and agricultural compounds, including 14C labeled phenol, 4-nitrophenol, pentachlorophenol, dimethyl parathion, parathion, chloropyrifos, fenthion, triazine, atrazine, simazine and propazine, and 24 solvent mixtures consisting of combinations of water, ethanol, propylene glycol, sodium lauryl sulphate and methyl nicotinate. Study methods included in vitro partitioning using isolated stratum corneum and permeability studies, Fourier transform infrared spectroscopy, multivariate clustering techniques, transmission electron microscopy and light microscopy. A model of dermal absorption was developed using a physiological-based (PBPK) approach. Ethanol and ethanol/water mixtures altered the stratum corneum through lipid extraction, rather than through disruption of lipid order. Partitioning was primarily determined by relative compound solubility between the stratum corneum lipids and the donor solvent. Permeability reflected the result of successive, complex processes and was not consistently correlated with stratum corneum partitioning. These results demonstrated the potential of using large datasets to identify consistent solvent and chemical mixture effects. Diffusion cell studies were conducted to validate the PBPK model under a variety of conditions including different dose ranges (6.3-106.9 mg/cm2 for parathion; 0.8-23.6 mg/cm2 for fenthion; 1.6-39.3 mg/cm2 for methyl parathion), different solvents (ethanol, 2-propanol and acetone), different solvent volumes (5-120 ml for ethanol; 20-80 ml for 2-propanol and acetone), occlusion versus open to atmosphere dosing, and corneocyte removal by tape-stripping. The study demonstrated the utility of PBPK models for studying dermal absorption, which can be useful as explanatory and predictive tools; and may be used for in silico hypotheses generation and limited hypotheses testing. These data have direct relevance to topical chemical exposure risk assessments

    Use of ethnoveterinary medicinal plants in cattle by Setswana-speaking people in the Madikwe area of the North West Province

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    Dissertation (MSc)--University of Pretoria, 2000.The role of plants in the treatment of disease and enhancement of production in animals in South African rural communities is poorly documented. Rapid Rural Appraisal (RRA) methods were employed to describe the use of ethnoveterinary medicinal plants in cattle by Setswana-speaking people in the Madikwe area of the North West Province of South Africa. Information was gathered from key spokespersons through individual interviews, group interviews, guided field walks and observations. Ethnoveterinary uses in cattle of 46 plant species representing 24 families were recorded. Plants were used in 84 % of the total number of ethnoveterinary remedies. These plants were used alone (64 %) or in mixtures (36 %) for 43 indications. The most important indications for the use of ethnoveterinary remedies were retained placenta, diarrhoea, gallsickness, fractures, eye inflammation, general ailments, fertility enhancement, general gastrointestinal problems, heartwater, internal parasites, coughing, redwater and the reduction of tick burdens. Plant materials were prepared in various ways including, infusion (36 %), decoction (33 %), infusion or decoction (13 %), ground fresh material (6 %), sap expressed from fresh material (3 %), charred (2 %) and dried (1 %). Unprocessed, fresh material was used in 6 % of remedies. The most common dosage form was a liquid for oral dosing (83 %). Other dosage forms included, drops, licks, ointments, lotions and powders. Liquid remedies for oral dosing were administered using a bottle. The study indicated that Setswana-speaking people in the North West Province have a rich heritage of ethnoveterinary knowledge, which includes all aspects of ethnoveterinary medicinal plant use. The impact of ethnoveterinary medicinal plant use on medicinal plant population densities was also assessed through a comparison of the medicinal plant densities inside and outside the Madikwe Game Reserve. Belt transects were used in a stratified trial design to record plant densities. No statistically significant differences in medicinal plant densities that could be attributed to medicinal plant use, were found.Paraclinical SciencesUnrestricte

    Using small unmanned aircraft systems for high spatial and temporal resolution characterizations of harmful algal blooms

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    Harmful algal blooms (HABs) are of toxicological interest because several genera of cyanobacteria, also known as blue‐green algae, have the ability to produce potent toxins that affect people, livestock, pets, and wildlife. Risk assessments based on traditional sampling methods are hampered by the sparseness of data points, and delays between sampling and the availability of results. These shortcomings of traditional sampling methods are highly significant when there is a need for actionable information at the spatial resolution of animal or human interactions with specific areas of a lake surface or lake shoreline, and within a timeframe that is relevant given the rapidly changing spatial distribution of algal blooms. Small unmanned aircraft systems (sUAS) provide a means of collecting spatially high resolution data on the surface densities of algae. Digital color‐infrared image data collected by an sUAS can be rapidly processed into information useful for risk assessment and risk management by converting image data into an index of algae density. In a proof‐of‐concept project, color‐infrared aerial images were collected using an sUAS fitted with a color‐infrared sensor, at three time points, from a section of Lake Centralia in Kansas, during a HAB formed by Microcystis aeruginosa cyanobacteria. The results revealed a high level of spatial and temporal variability in the HAB, and it clearly demonstrated the applicability of sUAS‐based aerial imaging to HAB characterization, at spatial and temporal resolutions relevant to localized and timely risk assessments

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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