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Endocrine Effects of Selective Serotonin Reuptake Inhibitors (SSRIs) on Aquatic Organisms
Marsha C. Black1, Emily D. Rogers1, and Theodore B. Henry2
1University of Georgia, Athens, GA;
2University of Tennessee, Knoxville, TN

Pharmaceutical products can contaminate surface waters after their prescribed medical use and have the potential to negatively affect aquatic organisms. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat clinical depression. Fluoxetine has been detected in surface waters at subparts-per-billion concentrations and also has been found to accumulate in tissues of fish from effluent dominated streams. Serotonin is an important neurotransmitter, and increased endogenous levels of serotonin resulting from exposure to SSRIs may affect a number of endocrine-mediated processes, including spawning, reproduction, and thyroid-mediated development. Experiments designed to detect endocrine effects of fluoxetine exposure were conducted on two model aquatic species: a fish (western mosquitofish, Gambusia affinis) and an amphibian (Xenopus laevis). In acute and chronic experiments, neonate western mosquitofish were exposed to aqueous fluoxetine (0.06-6,000 ppb) and effects on survival, sex ratio, and time to sexual maturity were evaluated. Fluoxetine was acutely toxic, and the concentration estimated to kill 50 percent of exposed neonates within 7 days was 614 ppb. Chronic exposure to concentrations less than or equal to 60 ppb did not significantly affect survival or sex ratio. Development of adult sexual morphology, however, was significantly delayed at this concentration by 2-3 weeks relative to control fish. Similar indicators of delayed development were observed in preliminary experiments with the African clawed frog, X. laevis. Time to metamorphosis was significantly delayed relative to controls following chronic exposure of tadpoles to 29.5 ppb fluoxetine. Upon reaching metamorphosis, frogs were significantly smaller at all exposure concentrations including 0.059 ppb, which is an environmentally relevant concentration. These experiments show the potential for fluoxetine to disrupt endocrine processes in fish and frogs and demonstrate the need for more targeted studies with fluoxetine and other SSRIs that measure endocrine biomarkers (e.g., hormones, histopathology of gonads and thyroid glands) on the exposed organisms.

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