One class of pharmaceutical compounds identified in U.S. and European waters are the B-adrenergic receptor blocking compounds (B-blockers). However, little information is available on the potential aquatic toxicity of these compounds. Therefore, Hyalella azteca, Daphnia magna, Ceriodaphnia dubia, and Oryias latipes (Japanese medaka) were exposed to metoprolol, nadolol, and propranolol to determine potential toxicity. Average 48-h LC(50) for propranolol to H. azteca was 29.8 mg/L. The no-observed-effects concentration (NOEC) and lowest-observed-effects concentration (LOEC) for propranolol affecting reproduction of H. azteca were 0.001 and 0.1 mg/L, respectively. The average propranolol and metoprolol 48-h LC(50)s for D. magna were 1.6 and 63.9 mg/L, respectively. C. dubia 48-h LC(50)s were 0.85 and 8.8 mg/L for propranolol and metoprolol, respectively. The NOEC and LOEC of propranolol affecting reproduction in C. dubia were 0.125 and 0.25 mg/L, respectively. In O. latipes, the propranolol 48-h LC(50) was 24.3 mg/L. Medaka growth was decreased at 0.5 mg/L propranolol. A 2-week medaka reproductive study indicated significant changes in plasma steroid levels; however, no changes in the average number of eggs produced or number of viable eggs which hatched was observed. In a 4-week follow-up propranolol exposure, the total number of eggs produced by medaka and the number of viable eggs that hatched were decreased at concentrations as low as 0.5 microg/L. Based on this study and the expected aqueous environmental exposure levels, adverse effects of propranolol to invertebrate populations is unlikely; however, further reproductive studies are need to elucidate the risk to teleosts.
The occurrence of environmental pharmaceutical products has recently received considerable attention, but impacts on the aquatic environment are largely unknown. Fluoxetine is a widely prescribed antidepressant and acts physiologically as a selective serotonin reuptake inhibitor (SSRI). To determine its potential to disrupt teleost reproductive function, Japanese medaka (Oryzias latipes) were exposed to fluoxetine at aqueous nominal concentrations of 0, 0.1, 0.5, 1 and 5 microg/L for 4 weeks. The last 14 days of this exposure included a reproductive assessment in which no significant changes were observed in egg production, rate of fertilization and spawning, or hatching success of fertilized eggs. A low incidence (1.97-2.53%; 4.02-5.16-fold greater than controls) of developmental abnormalities was observed in offspring from all fluoxetine treatments. Adult gonadal somatic index, hepatic vitellogenin, and ex vivo gonadal steroidogenesis were also unaffected. Circulating plasma estradiol levels in females were significantly increased by 0.1 and 0.5 microg/L treatments. Our study provides novel information on fish biochemical, physiological, and reproduction responses to environmentally realistic fluoxetine concentrations.
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