Metabolomic analysis predicted changes in growth rate in Daphnia magna exposed to acetaminophen

As urbanization and the global population increases, pollutants associated with municipal wastewater such as pharmaceuticals are becoming more prevalent in aquatic environments. Acetaminophen (paracetamol) is a widely used drug worldwide and one of the most frequently detected pharmaceuticals in freshwater ecosystems. This study investigated the impact of acetaminophen on the metabolite profile of Daphnia magna at two life stages; and used these metabolomic findings to hypothesize a potential impact at a higher organismal level which was subsequently tested experimentally. Targeted polar metabolite analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure changes in the concentration of 51 metabolites in the neonate (> 24 h old) and adult (8 day-old) daphnids following a 48-h exposure to sub-lethal concentrations of acetaminophen. The impact of acetaminophen on the metabolic profile of neonates was widely different from adults. Also, acetaminophen exposure perturbed the abundance of nucleotides more extensively than other metabolites. The acute metabolomic experimental results led to the hypotheses that exposure to sub-lethal concentrations of acetaminophen upregulates protein synthesis in D. magna and subsequently increases growth during early life stages and has an opposite impact on adults. Accordingly, a 10 day growth rate experiment indicated that exposure to acetaminophen elevated biomass production in neonates but not in adults. These novel findings demonstrate that a targeted analysis and interpretation of the changes in the polar metabolic profile of organisms in response to environmental stressors could be used as a tool to predict changes at higher biological levels. As such, this study further emphasizes the incorporation of molecular-level platforms as critical and robust tools in environmental assessment frameworks and biomonitoring of aquatic ecosystems.