Fish on Prozac (and Zoloft): ten years later.

A decade has now passed since our research group initially reported several adverse effects of fluoxetine to aquatic organisms commonly employed for developing environmental quality criteria, evaluating whole effluent toxicity, and monitoring ambient toxicity of surface waters and sediments. Our subsequent observation of fluoxetine, sertraline and their active metabolites (norfluoxetine and desmethylsertraline, respectively) accumulating in muscle, liver and brain tissues of three different fish species from an effluent-dominated stream was termed "Fish on Prozac." Here I briefly review some scientific lessons learned from our study of antidepressants and the environment, including opportunities for research, management, environmental education and public outreach. Intrinsic chemical properties of antidepressants and other pharmaceuticals have afforded research in areas ranging from analytical chemistry and comparative pharmacology, to influences of ionization, chirality and adverse outcome pathways on hazard and risk assessment, and further promises to support sustainable molecular design of less hazardous chemicals. Using probabilistic hazard assessment and fish plasma modeling approaches, selective serotonin reuptake inhibitors and tricyclic antidepressants are predicted to result in therapeutic hazard to fish (internal fish plasma level equaling mammalian therapeutic dose) when exposed to water (inhalational) at or below 1μg/L, a common trigger value for environmental assessments. Though many questions remain unanswered, studies of antidepressants in urbanizing aquatic systems have provided, and will continue to develop, an advanced understanding of environmental hazards and risks from pharmaceuticals and other contaminants.