(PM273) Daphnia magna responses to Fluoxetine and Propranolol mixtures.

Glidewell, E1, Ramirez, A1, Chambliss, C1, Brooks, B1, 1 Baylor University, Waco, Tx, USA

ABSTRACT- Environmental effects data for many pharmaceuticals is limited and is typically based on traditional, relatively short term ecotoxicological studies. This approach may not be best suited for determination of potential effects from environmental pharmaceutical exposure, as pharmaceuticals in effluent-dominated streams present low level, relatively continuous exposure to complex mixtures. Of particular interest is potential mixture effects of compounds utilizing similar metabolic pathways, such as Cytochrome P450s. Fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor, and Propranolol, a commonly prescribed beta adrenergic blocker, are not co-prescribed in humans because both compounds are metabolized by CYP450 2D6. Fluoxetine is known to inhibit this isoenzyme, thus influencing metabolism and clearance rates of Propranolol. To assess potential responses of Daphnia magna to mixtures of these compounds, traditional 96 hr acute tests and 21 day chronic survival, growth and reproduction tests were performed. Nominal treatment levels were verified by LC-MS. Fluoxetine and Propranolol LC50s at 48 and 96 hrs were estimated to be 2350 and 650 g/L, and 1723 and 1121g/L, respectively. Interestingly, the addition of 125, 250, and 500 g/L Fluoxetine to acute Propranolol toxicity tests decreased the average 96 hr LC50 from 1121 g/L (Propranolol only) to 497, 462 and 157 g/L, respectively. Our results indicate that interactive toxicity should be considered when assessing environmental hazard of pharmaceuticals. Further, future studies should investigate responses of aquatic invertebrates to pharmaceutical mixtures.

Key words: fluoxetine, pharmaceutical mixtures, propranolol , Daphnia magna

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