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() Enantiomeric specific toxicity of propranolol to Daphnia magna.
Stanley, J1, Ramirez, A1, Dzialowski, E2, Chambliss, C1, Brooks, B1, 1 Baylor University, Waco, TX, USA2 University of North Texas, Denton, TX, USA
ABSTRACT- Propranolol is a non-selective 
-adrenergic receptor blocking agent that is primarily prescribed for the treatment of angina, hypertension, severe anxiety, and abnormal heart rhythms. Propranolol has been detected in municipal effluents at levels ranging from the low ppt to the low ppb range. Like many therapeutics and other aquatic contaminants, propranolol is distributed as a racemic mixture ((R/S)-propranolol hydrochloride). Although the S-enantiomer is known to be the most active form in mammals, no information is available on the enantiomeric toxicity of propranolol to aquatic organisms. Daphnia magna acute and chronic studies were conducted in order to determine enantiomeric specific toxicity of propranolol to a model invertebrate. Propranolol treatment levels were verified using by LC-MS; mean percent recovery was 106% (±8%). Average propranolol LC50s for the acute studies were similar ((S): 1399 ppb; (R): 1572 ppb; (R/S): 1665 ppb). Although the (S)-enantiomer was the most acutely toxic compound tested, chronic D. magna responses to propranolol enantiomers followed the relationship: (R)-enantiomer (most toxic) > (R/S) mixture > (S)-enantiomer (least toxic). Interestingly, the 197 and 51 ppb treatment levels of (R)-propranolol produced statistically significant increases in reproduction. While recent studies indicate that mammalian pharmacological safety information may be useful to predict fish responses to propranolol and other therapeutics, extrapolations of enantiomeric propranolol activity from vertebrates to predict standard ecotoxicity test responses in cladocerans, and potentially other invertebrates, are not warranted at this time.
Key words: enantiomer, propranolol, pharmaceuticals, Daphnia magna