A new approach to toxicity testing in Daphnia magna: application of high throughput FT-ICR mass spectrometry metabolomics

作者：Taylor Nadine S; Weber Ralf J M; Southam Andrew D; Payne Tristan G; Hrydziuszko Olga; Arvanitis Theodoros N; Viant Mark R^*

来源：Metabolomics, 2009, 5(1): 44-58.

DOI：10.1007/s11306-008-0133-3

• Metabonomics
• Environmental metabolomics
• Water flea
• Tiered testing
• Risk assessment
• SIM-stitching

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 mu g dry mass) or a single adult daphnid (301 mu g dry mass). An OECD 24 h acute toxicity test was conducted with neonates at copper concentrations of 0, 5, 10, 25, 50 mu g 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.

• 出版日期2009-3