title: Metabolic Effect Level Index Links Multivariate Metabolic Fingerprints to Ecotoxicological Effect Assessment.
abstract: A major goal of ecotoxicology is the prediction of adverse outcomes for populations from sensitive and early physiological responses. A snapshot of the physiological state of an organism can be provided by metabolic fingerprints. However, to inform chemical risk assessment, multivariate metabolic fingerprints need to be converted to readable end points suitable for effect estimation and comparison. The concentration- and time-dependent responsiveness of metabolic fingerprints to the PS-II inhibitor isoproturon was investigated by use of a Myriophyllum spicatum bioassay. Hydrophilic and lipophilic leaf extracts were analyzed with gas chromatography-mass spectrometry (GC-MS) and preprocessed with XCMS. Metabolic changes were aggregated in the quantitative metabolic effect level index (MELI), allowing effect estimation from Hill-based concentration-response models. Hereby, the most sensitive response on the concentration scale was revealed by the hydrophilic MELI, followed by photosynthetic efficiency and, 1 order of magnitude higher, by the lipophilic MELI and shoot length change. In the hydrophilic MELI, 50% change compares to 30% inhibition of photosynthetic efficiency and 10% inhibition of dry weight change, indicating effect development on different response levels. In conclusion, aggregated metabolic fingerprints provide quantitative estimates and span a broad response spectrum, potentially valuable for establishing adverse outcome pathways of chemicals in environmental risk assessment.
authors.affiliation: †Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
authors.forename: Janet
authors.initials: J
authors.lastname: Riedl
authors.affiliation: †Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Schreiber
authors.affiliation: ‡Technische Universität Bergakademie Freiberg, Leipziger Straße 29, 09599 Freiberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Otto
authors.affiliation: ‡Technische Universität Bergakademie Freiberg, Leipziger Straße 29, 09599 Freiberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Heilmeier
authors.affiliation: †Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Altenburger
authors.affiliation: †Helmholtz Centre for Environmental Research - UFZ, Permoserstraße 15, 04318 Leipzig, Germany.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Schmitt-Jansen
mesh_terms: D054750:Ecotoxicology; D019684:Magnoliopsida / Q000187:drug effects / Q000378:metabolism*; D055442:Metabolome / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D008962:Models, Theoretical; D015999:Multivariate Analysis; D010671:Phenylurea Compounds / Q000494:pharmacology; D010788:Photosynthesis / Q000187:drug effects; D025341:Principal Component Analysis
chemical_list: D010671:Phenylurea Compounds; C028904:isoproturon