Sertraline Hydrochloride Exposure Leads to Reactive Oxygen Species Burst in Model Microalgae Species ( <i>Raphidocelis subcapitata</i> )

Microalgae play important ecological roles and serve as useful models for assessing the impacts of environmental contaminants on lower trophic aquatic organisms. Sertraline, a commonly prescribed selective serotonin reuptake inhibitor (SSRI) found in urban waters, has been observed to induce chlorosis in <i>Raphidocelis subcapitata</i> close to environmentally relevant concentrations. This study estimated potentially hazardous concentrations of sertraline hydrochloride by deriving transcriptomic and metabolomic points of departure (tPODs and mPODs) below which chronic adverse effects would not be expected. Additionally, an Adverse Outcome Pathway describing the mechanism by which sertraline hydrochloride impacted <i>R. subcapitata</i> was proposed using a multiomics approach. The mPOD derived from nontargeted metabolomics was comparable to the tPOD (455 vs 690 μg/L), and annotated dysregulated metabolites along with reduced photosynthetic capability indicated that uncoupling of the cyclic electron flow required for photosynthesis led to a reactive oxygen species (ROS) burst. This probable ROS burst altered cell membrane composition and downregulated genes associated with protoporphyrinogen IX and heme biosynthesis pathways. This research highlights the molecular mechanisms underlying pharmaceutical-induced chlorosis in a model microalgae species and demonstrates the utility of integrating metabolomics and transcriptomics for assessing the potential ecological risks of SSRIs.