Unveiling Subthreshold Hormesis of Antibiotics in Global Waters

Low-dose antibiotics may pose ecological risk by inducing hormesis, an emerging concern largely overlooked by ecological risk assessment (ERA) guidelines worldwide. This study compiled data sets on antibiotic-induced hormesis and water concentrations to integrate hormesis into the ERA of antibiotics and explore its global implications. A hormesis data set comprising 3,149 dose-response observations was gathered, covering 57 antibiotics and 72 aquatic species. The standardized hormetic amplitudes followed a three-parameter log-normal distribution and were mainly driven by the species tested. Further comparison revealed overlaps between hormesis-triggered doses and predicted no-effect concentrations (PNECs), highlighting the unrecognized subthreshold effects. Promisingly, a pathway for incorporating hormesis into ERA was proposed, introducing two hormesis-based risk thresholds, the predicted no-stimulation concentration (PNSC) and the predicted no-inhibition concentration (PNIC). Realistically, 89,612 antibiotic records were identified in global waters for compounds inducing hormesis, with 8% reaching the lowest induction doses. Global risk assessment indicated that antibiotic concentrations were generally below the conventional PNEC, while regions exceeding the PNSC and PNIC were widespread, with the spatial distribution of risk areas expanded under more stringent assessment factors. Collectively, the integration of hormesis into ERA enhances the characterization of subthreshold risks and facilitates the detection of early warning signals from low-dose antibiotic contamination.