Validation of metabolomics for toxic mechanism of action screening with the earthworm Lumbricus rubellus

Guo, Qi; Sidhu, Jasmin K.; Ebbels, Timothy M.D.; Rana, Faisal; Spurgeon, David J. ORCID:; Svendsen, Claus ORCID:; Sturzenbaum, Stephen R.; Kille, Peter; Morgan, A. John; Bundy, Jacob G.. 2009 Validation of metabolomics for toxic mechanism of action screening with the earthworm Lumbricus rubellus. Metabolomics, 5 (1). 72-83.

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One of the promises of environmental metabolomics, together with other ecotoxicogenomic approaches, is that it can give information on toxic compound mechanism of action (MOA), by providing a specific response profile or fingerprint. This could then be used either for screening in the context of chemical risk assessment, or potentially in contaminated site assessment for determining what compound classes were causing a toxic effect. However for either of these two ends to be achievable, it is first necessary to know if different compounds do indeed elicit specific and distinct metabolic profile responses. Such a comparative study has not yet been carried out for the earthworm Lumbricus rubellus. We exposed L. rubellus to sub-lethal concentrations of three very different toxicants (CdCl2, atrazine, and fluoranthene, representing three compound classes with different expected MOA), by semi-chronic exposures in a laboratory test, and used NMR spectroscopy to obtain metabolic profiles. We were able to use simple multivariate pattern-recognition analyses to distinguish different compounds to some degree. In addition, following the ranking of individual spectral bins according to their mutual information with compound concentrations, it was possible to identify both general and specific metabolite responses to different toxic compounds, and to relate these to concentration levels causing reproductive effects in the worms.

Item Type: Publication - Article
Digital Object Identifier (DOI):
Programmes: CEH Topics & Objectives 2009 - 2012 > Biogeochemistry > BGC Topic 3 - Managing Threats to Environment and Health
UKCEH and CEH Sections/Science Areas: Hails
ISSN: 1573-3882
Additional Keywords: Environmental biomarker, Atrazine, Cadmium, Fluoranthene, Ecotoxicogenomics, Metabonomics
NORA Subject Terms: Biology and Microbiology
Ecology and Environment
Date made live: 28 Apr 2009 09:29 +0 (UTC)

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