Metabolomics discovers early-response metabolic biomarkers that can predict chronic reproductive fitness in individual daphnia magna

Research output: Contribution to journalArticlepeer-review

Authors

Colleges, School and Institutes

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.

Details

Original languageEnglish
Article number42
Number of pages19
JournalMetabolites
Volume8
Issue number3
Early online date23 Jul 2018
Publication statusPublished - 1 Sep 2018

Keywords

  • Adverse outcome, AOP, DIMS, Direct infusion mass spectrometry, Key event, MoA, OECD test guideline, Omics, PLS regression, Toxicogenomics