Original Article

Metabolomics

, Volume 5, Issue 1, pp 72-83

First online:

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

  • Qi GuoAffiliated withDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology, and Anaesthetics, Faculty of Medicine, Imperial College London
  • , Jasmin K. SidhuAffiliated withDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology, and Anaesthetics, Faculty of Medicine, Imperial College London
  • , Timothy M. D. EbbelsAffiliated withDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology, and Anaesthetics, Faculty of Medicine, Imperial College London
  • , Faisal RanaAffiliated withDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology, and Anaesthetics, Faculty of Medicine, Imperial College London
  • , David J. SpurgeonAffiliated withCentre for Ecology and Hydrology
  • , Claus SvendsenAffiliated withCentre for Ecology and Hydrology
  • , Stephen R. StürzenbaumAffiliated withPharmaceutical Science Division, King’s College London, School of Biomedical & Health Sciences
  • , Peter KilleAffiliated withUniversity of Cardiff, School of Biosciences
  • , A. John MorganAffiliated withUniversity of Cardiff, School of Biosciences
    • , Jacob G. BundyAffiliated withDepartment of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology, and Anaesthetics, Faculty of Medicine, Imperial College London Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

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.

Keywords

Environmental biomarker Atrazine Cadmium Fluoranthene Ecotoxicogenomics Metabonomics