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Metabolites 2018, 8(3), 42; https://doi.org/10.3390/metabo8030042

Metabolomics Discovers Early-Response Metabolic Biomarkers that Can Predict Chronic Reproductive Fitness in Individual Daphnia magna

School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
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Received: 30 May 2018 / Revised: 9 July 2018 / Accepted: 18 July 2018 / Published: 23 July 2018
(This article belongs to the Special Issue Metabolomics in Toxicology)
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Abstract

Chemical risk assessment remains entrenched in chronic toxicity tests that set safety thresholds based on animal pathology or fitness. Chronic tests are resource expensive and lack mechanistic insight. Discovering a chemical’s mode-of-action can in principle provide predictive molecular biomarkers for a toxicity endpoint. Furthermore, since molecular perturbations precede pathology, early-response molecular biomarkers may enable shorter, more resource efficient testing that can predict chronic animal fitness. This study applied untargeted metabolomics to attempt to discover early-response metabolic biomarkers that can predict reproductive fitness of Daphnia magna, an internationally-recognized test species. First, we measured the reproductive toxicities of cadmium, 2,4-dinitrophenol and propranolol to individual Daphnia in 21-day OECD toxicity tests, then measured the metabolic profiles of these animals using mass spectrometry. Multivariate regression successfully discovered putative metabolic biomarkers that strongly predict reproductive impairment by each chemical, and for all chemicals combined. The non-chemical-specific metabolic biomarkers were then applied to metabolite data from Daphnia 24-h acute toxicity tests and correctly predicted that significant decreases in reproductive fitness would occur if these animals were exposed to cadmium, 2,4-dinitrophenol or propranolol for 21 days. While the applicability of these findings is limited to three chemicals, they provide proof-of-principle that early-response metabolic biomarkers of chronic animal fitness can be discovered for regulatory toxicity testing. View Full-Text
Keywords: DIMS; direct infusion mass spectrometry; omics; toxicogenomics; OECD test guideline; AOP; key event; adverse outcome; MoA; PLS regression DIMS; direct infusion mass spectrometry; omics; toxicogenomics; OECD test guideline; AOP; key event; adverse outcome; MoA; PLS regression
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Taylor, N.S.; Gavin, A.; Viant, M.R. Metabolomics Discovers Early-Response Metabolic Biomarkers that Can Predict Chronic Reproductive Fitness in Individual Daphnia magna. Metabolites 2018, 8, 42.

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