Novel approaches to toxicity testing in Daphnia magna

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http://eprints.org/relation/isVolatileVersionOf http://etheses.bham.ac.uk/id/document/1627 http://eprints.org/relation/ispreviewThumbnailVersionOf http://etheses.bham.ac.uk/id/document/1627 http://eprints.org/relation/isVersionOf http://etheses.bham.ac.uk/id/document/1627 archive 4031 disk0/00/00/06/68 2010-05-19 10:33:38 2019-01-23 09:52:36 2011-07-19 16:21:14 thesis show 0 Taylor Nadine Suzanne Viant Mark University of Birmingham Novel approaches to toxicity testing in Daphnia magna unpub QH301 10col_life Current regulatory risk assessment strategies have several limitations, such as linking subcellular changes to higher-level biological effects, and an improved knowledge-based approach is needed. Ecotoxicogenomic techniques have been proposed as having the potential to overcome the current limitations, providing greater mechanistic information for ecotoxicological testing. In this thesis, metabolomics is explored as a novel method for toxicity testing using Daphnia magna. Initially I evaluated the potential application of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) based metabolomics for use in regulatory toxicity testing. Subsequently, I aimed to use this approach to discriminate between toxicant modes of action (MOA) and to link toxicant induced metabolic effects to reduced reproductive output in D. magna. FT-ICR MS metabolomics was determined to be a feasible approach for toxicity testing of both whole-organism homogenates and haemolymph of D. magna. It is capable of discriminating between life-stages of D. magna as well as determining toxicant-induced metabolic effects. Highly predictive multivariate classification models were capable of significantly discriminating between four different toxicant MOAs; achievable in both haemolymph and whole-organism extracts, with the latter being the more information-rich sample type. Multivariate regression models were predictive of reduced reproductive output in D. magna following toxicant exposure, and determined that a metabolic biomarker signature was significantly able to predict the reproductive output of D. magna. Ultimately this research has concluded that an FT-ICR MS metabolomics approach for use in regulatory toxicity testing using Daphnia magna is both viable and can provide valuable information. 2010-07 2010-03 graduation eng author unchecked This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. public 330 University of Birmingham School of Biosciences d_ph nerc 2010-07 graduation