Toxicity of Select Beta Adrenergic Receptor-Blocking Pharmaceuticals (B-Blockers) on Aquatic Organisms

Abstract

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.

Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment

“…Accordingly, the acute toxicity of propranolol, metoprolol and nadolol was assessed on the invertebrates H. azteca, D. magna, D. lumholtzi and C. dubia. Following a 48-h exposure to propranolol, LC50 values of 29.8, 1.6 and 0.8 mg L −1 were obtained for H. azteca, D. magna and C. dubia respectively [172] while acute exposure to nadolol did not affect the survival of the invertebrates [172]. Regarding meto-prolol, D. magna and C. dubia exhibited LC50 values of 63.9 and 8.8 mg L −1 , respectively [172].…”

“…However, Cleuvers [175] obtained a higher EC50 value (438 mg L −1 ) in an acute toxicity test performed on D. magna. Reproduction in invertebrates decreased following propranolol exposure with NOEC values of 1 and 125 µg L −1 for H. azteca and C. dubia respectively [172]. Propranolol inhibited the growth of the green algae Desmodesmus subspicatus, showing an EC50 of 7.7 mg L −1 [175] while atenolol almost failed to reg-ister a toxic effect (EC50 of 620 mg L −1 ).…”

“…Fish, like other vertebrates, possess �-receptors in the heart, liver and reproductive system [170,171] so that pro-longed exposure to drugs belonging to this therapeutic class may cause deleterious effects. From a two weeks study, it was observed that exposure to 500 µg L −1 of propranolol reduced growth rates of Japanese medaka [172]. Plasma steroid levels were altered in both male and female fish even at concentrations as low as 1 µg L −1 pro-pranolol.…”

“…Following a 48-h exposure to propranolol, LC50 values of 29.8, 1.6 and 0.8 mg L −1 were obtained for H. azteca, D. magna and C. dubia respectively [172] while acute exposure to nadolol did not affect the survival of the invertebrates [172]. Regarding meto-prolol, D. magna and C. dubia exhibited LC50 values of 63.9 and 8.8 mg L −1 , respectively [172]. However, Cleuvers [175] obtained a higher EC50 value (438 mg L −1 ) in an acute toxicity test performed on D. magna.…”

Repeating History: Pharmaceuticals in the Environment

“…Limited data for other MOA classes of pharmaceuticals suggest that this phenomenon is not restricted to HPG-active steroids. For example, Huggett et al (23) reported an ACR in fish of ~50,000 for propranolol, a -blocker. These examples illustrate that for pharmaceuticals with a targeted MOA in conserved biological pathways, acute toxicity test data can be inadequate for predicting ecological risks.…”