Evaluation of pesticide toxicity: a hierarchical QSAR approach to model the acute aquatic toxicity and avian oral toxicity of pesticides

The thesis aimed to extract information relevant to the hazard and risk assessment of pesticides. In particular, quantitative structure-activity relationship (QSAR) approaches have been used to build up a mathematical model able to predict the aquatic acute toxicity, LC50, and the avian oral toxicity, LD50, for pesticides. Ecotoxicological values were collected from several databases, and screened according to quality criteria. A hierarchical QSAR approach was applied for the prediction of acute aquatic toxicity. Chemical structures were encoded into molecular descriptors by an automated, seamless procedure available within the OpenMolGRID system. Different linear and non-linear regression techniques were used to obtain reliable and thoroughly validated QSARs. The final model was developed by a counter-propagation neural network coupled with genetic algorithms for variable selection. The proposed QSAR is consistent with McFarland's principle for biological activity and makes use of seven molecular descriptors. The model was assessed thoroughly in test (R2 = 0.8) and validation sets (R2 = 0.72), the y-scrambling test and a sensitivity/stability test. The second endpoint considered in this thesis was avian oral toxicity. As previously, the chemical description of chemicals was generated automatically by the OpenMolGRID system. The best classification model was chosen on the basis of the performances on a validation set of 19 data points, and was obtained from a support vector machine using 94 data points and nine variables selected by genetic algorithms (Error Ratetraining = 0.021, Error Ratevalidation = 0.158). The model allowed for a mechanistic estimation of the toxicological action. In fact, several descriptors selected for the final classification model encode for the interaction of the pesticides with other molecules. The presence of hetero-atoms, e.g. sulphur atoms, is correlated with the toxicity, and the pool of descriptor selected is generally dependent from the 3D conformation of the structures. These suggest that, in the case of avian oral toxicity, pesticides probably exert their toxic action through the interaction with some macromolecule and/or protein of the biological system

Developmental neurotoxicity testing of chemical mixtures in zebrafish embryos

Developmental neurotoxicity (DNT) is an understudied problem. Every day, people are exposed to complex mixtures of several chemical substances via food intake, inhalation and dermal contact. Nevertheless, risk assessment is performed on single compounds only under the assumption that the individual exposure levels (below no observed adverse effect levels, NOAELs) are predictive of the mixture effect. In the EuroMix project, a method has been developed to evaluate the effects of mixtures of substances, even at or below NOAELs. This method follows the strategy proposed by the European Food Safety Authority (EFSA), and further implements the Adverse Outcome Pathway (AOP) concept as a basis. Currently, assessment of the DNT potential of compounds is performed in costly and time-consuming in vivo rodent studies involving a large number of animals studied over more than one generation. Therefore, from a 3Rs (Replacement, Reduction, Refinement) perspective an alternative approach is needed. The zebrafish (Danio rerio) embryo (ZFE) provides an interesting and potentially useful model to study DNT as neurodevelopment occurs fast with a large resemblance to the higher vertebrate including the human system. Also, from a legal perspective, experimental work with zebrafish embryos within 120 hours post-fertilization, is not considered an animal experiment. Combined with the ease of culture and the high reproduction rate this renders the ZFE a suitable model for high throughput DNT testing in vitro. One of the suitable readouts for DNT testing is neurobehavior since it provides integrated information on the functionality/status of the full nervous system of the embryo. Within 120 hpf the embryo develops from a fertilized egg to a fully functional embryo responsive to environmental stimuli such as light and sound (vibration). The present Ph.D. study investigated the potential human health risk caused by the simultaneous exposure of chemical substances and the need to include the mixtures in the risk assessment. To obtain a real-life picture ofenvironmental pollution by chemical mixtures, an UHPLC-MS/MS-MRM method was developed and validated for screeining pesticide residues on raw and processed tomatoes. Then, the attention was focused on the potential use of the zebrafish model for assessing the chemical mixtures effects in DNT. Recognised that pharmaceuticals display a well-known MOA and are known to cause DNT, their use as model compounds instead of pesticides was preferred. Therefore, the combined effect of three psychoactive pharmaceuticals of concern, Carbamazepine (CBZ), Fluoxetine (FLX), Venlafaxine (VNX) and their main metabolites, Carbamazepine 10,11 -epoxide (CBZ 10,11E), Norfluoxetine (norFLX), and Desvenlafaxine (desVNX), was studied using the zebrafish embryos as a study model. At first, single-compound concentration-effect relationships were assessed as input for dose-response modelling following the benchmark approach leading to a classification of compounds based on potency. Subsequently, a binary mixture was composed based on the relative potency of the individual compounds and tested for their effect on neurological development. To support the assessment of developmental neurotoxicity, the gene expression of three specific DNT markers was investigated

Undergraduate and Graduate Course Descriptions, 2008 Summer

Wright State University undergraduate and graduate course descriptions from Summer 2008

Information retrieval and text mining technologies for chemistry

Efficient access to chemical information contained in scientific literature, patents, technical reports, or the web is a pressing need shared by researchers and patent attorneys from different chemical disciplines. Retrieval of important chemical information in most cases starts with finding relevant documents for a particular chemical compound or family. Targeted retrieval of chemical documents is closely connected to the automatic recognition of chemical entities in the text, which commonly involves the extraction of the entire list of chemicals mentioned in a document, including any associated information. In this Review, we provide a comprehensive and in-depth description of fundamental concepts, technical implementations, and current technologies for meeting these information demands. A strong focus is placed on community challenges addressing systems performance, more particularly CHEMDNER and CHEMDNER patents tasks of BioCreative IV and V, respectively. Considering the growing interest in the construction of automatically annotated chemical knowledge bases that integrate chemical information and biological data, cheminformatics approaches for mapping the extracted chemical names into chemical structures and their subsequent annotation together with text mining applications for linking chemistry with biological information are also presented. Finally, future trends and current challenges are highlighted as a roadmap proposal for research in this emerging field.A.V. and M.K. acknowledge funding from the European Community’s Horizon 2020 Program (project reference: 654021 - OpenMinted). M.K. additionally acknowledges the Encomienda MINETAD-CNIO as part of the Plan for the Advancement of Language Technology. O.R. and J.O. thank the Foundation for Applied Medical Research (FIMA), University of Navarra (Pamplona, Spain). This work was partially funded by Consellería de Cultura, Educación e Ordenación Universitaria (Xunta de Galicia), and FEDER (European Union), and the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684). We thank Iñigo Garciá -Yoldi for useful feedback and discussions during the preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Undergraduate and Graduate Course Descriptions, 2006 Fall

Wright State University undergraduate and graduate course descriptions from Fall 2006

Undergraduate and Graduate Course Descriptions, 2007 Fall

Wright State University undergraduate and graduate course descriptions from Fall 2007

Undergraduate and Graduate Course Descriptions, 2007 Winter

Wright State University undergraduate and graduate course descriptions from Winter 2007

General Catalog 2009-2010

Contains course descriptions, University college calendar, and college administrationhttps://digitalcommons.usu.edu/universitycatalogs/1128/thumbnail.jp

Aerospace medicine and biology: A cumulative index to the 1986 issues (supplement 293)

This publication is a cumulative index to the abstracts contained in the Supplements 281 through 292 of Aerospace Medicine and Biology: A Continuing Bibliography. It includes seven indexes - subject, personal author, corporate source, foreign technology, contract number, report number, and accession number