Abstract
DEET is one of the most frequently detected insect repellents in the environment reaching concentrations of several μg L 1 in surface water. There is scarce information available regarding its mode of action in non-target organisms. Here, we have used an integrated metabolomic and transcriptomic approach to elucidate the possible adverse effects of DEET exposure in the marine fish gilthead sea bream (Sparus aurata). Individuals were exposed at an environmentally relevant concentration of DEET (10 μg L 1) for 22 days in a continuous flow-through system. Transcriptomic analysis revealed 250 differentially expressed genes in liver, while metabolomic analysis identified 190 differentially modulated features in liver and 98 in plasma. Multi-omic data integration and visualization allowed elucidation of the modes of action of DEET exposure, including: energy depletion through the disruption of carbohydrate and amino acids metabolisms, oxidative stress leading to DNA damage, lipid peroxidation, and damage to cell membrane and apoptosis. Activation of xenobiotic pathway as well as the inmune-inflammatory reaction was evidenced in the present work.