A new approach to toxicity testing in Daphnia magna: application of high throughput FT-ICR mass spectrometry metabolomics |
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Authors: | Nadine S Taylor Ralf J M Weber Andrew D Southam Tristan G Payne Olga Hrydziuszko Theodoros N Arvanitis Mark R Viant |
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Institution: | (1) School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK;(2) Centre for Systems Biology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK;(3) School of Electronic, Electrical & Computer Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK |
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Abstract: | Currently there is a surge of interest in exploiting toxicogenomics to screen the toxicity of chemicals, enabling rapid and
accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further testing. Direct
infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only
15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna, is an OECD test species and is utilised internationally for toxicity testing. However, no metabolomics studies of this species
have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for toxicity
testing in D. magna. We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (<24 h old; 224 μg dry mass) or a
single adult daphnid (301 μg dry mass). An OECD 24 h acute toxicity test was conducted with neonates at copper concentrations
of 0, 5, 10, 25, 50 μg l−1. A total of 5447 unique peaks were detected reproducibly, of which 4768 were assigned at least one empirical formula and
1017 were putatively identified based upon accurate mass measurements. Significant copper-induced changes to the daphnid metabolome,
consistent with the documented MOA of copper, were detected thereby validating the approach. In addition, N-acetylspermidine was putatively identified as a novel biomarker of copper toxicity. Collectively, our results highlight the
excellent sensitivity, reproducibility and mass accuracy of FT-ICR mass spectrometry, and provide strong evidence for its
applicability to high-throughput screening of chemical toxicity in D. magna.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. |
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Keywords: | Metabonomics Environmental metabolomics Water flea Tiered testing Risk assessment SIM-stitching |
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