The Good, the Bad, and the Toxic: Approaching Hormesis in <i>Daphnia magna</i> Exposed to an Energetic Compound

A hormetic response is characterized by an opposite effect in small and large doses of chemical exposure, often resulting in seemingly beneficial effects at low doses. Here, we examined the potential mechanisms underlying the hormetic response of <i>Daphnia magna</i> to the energetic trinitrotoluene (TNT). <i>Daphnia magna</i> were exposed to TNT for 21 days, and a significant increase in adult length and number of neonates was identified at low concentrations (0.002–0.22 mg/L TNT), while toxic effects were identified at high concentrations (0.97 mg/L TNT and above). Microarray analysis of <i>D. magna</i> exposed to 0.004, 0.12, and 1.85 mg/L TNT identified effects on lipid metabolism as a potential mechanism underlying hormetic effects. Lipidomic analysis of exposed <i>D. magna</i> supported the hypothesis that TNT exposure affected lipid and fatty acid metabolism, showing that hormetic effects could be related to changes in polyunsaturated fatty acids known to be involved in <i>Daphnia</i> growth and reproduction. Our results show that <i>Daphnia</i> exposed to low levels of TNT presented hormetic growth and reproduction enhancement, while higher TNT concentrations had an opposite effect. Our results also show how a systems approach can help elucidate potential mechanisms of action and adverse outcomes