Toxicity and enantiospecific differences of two β-blockers, propranolol and metoprolol, in the embryos and larvae of zebrafish (Danio rerio).
Propranolol is a widely prescribed, nonselective beta-adrenergic receptor-blocking agent. Propranolol has been detected in municipal effluents from the ng/L to the low-microg/L range. Like many therapeutics and other aquatic contaminants, propranolol is distributed as a racemic mixture ((R,S)-propranolol hydrochloride). Although the (S)-enantiomer is the most active form in mammals (up to 100-fold difference), no information is available regarding the enantiospecific toxicity of propranolol to aquatic organisms. Acute and chronic studies were conducted with Daphnia magna and Pimephales promelas to determine enantiospecific toxicity of propranolol to a model aquatic invertebrate and vertebrate, respectively. Also, enantiospecific effects of propranolol on D. magna heart rate were examined. Propranolol treatment levels were verified using high-performance liquid chromatography/mass spectrometry. Acute (48-h) responses of both organisms were similar for all enantiomer treatments. Chronic P. promelas responses to propranolol enantiomers followed the hypothesized relationship of (S)-propranolol being more toxic than (R)-propranolol, but chronic D. magna responses did not. This is potentially the result of a lack of beta-type receptors in cladocerans. No enantiospecific effects on daphnid heart rate were observed in acute exposures. Interestingly, some propranolol enantiomer treatments produced significant increases in reproduction before causing reproduction to decrease at higher treatment levels. To our knowledge, this research represents the first study of enantiospecific toxicity of chiral pharmaceutical pollutants.