Occurrence, ecotoxicological effects and risk assessment of antihypertensive pharmaceutical residues in the aquatic environment--A review.

This study presents a review of the investigated antihypertensives in different aquatic compartments. It aims to compare these data with those regarding ecotoxicity effects in order to find out ecotoxicological data gaps for these pharmaceuticals and to point out the need for future studies. In addition, part of this article is dedicated to the risk assessment of the parent compounds atenolol, metoprolol, propranolol and verapamil, which are of great environmental concern in terms of contamination levels and for which there are sufficient ecotoxicological data available. 79 articles were retrieved presenting quantization data for 34 different antihypertensives and/or their metabolites. Only 43 articles were found regarding acute and chronic ecotoxicological effects of antihypertensive drugs. The results indicated that the beta-blockers atenolol, metoprolol and propranolol are the antihypertensives most frequently detected in the aquatic environment. They are also the drugs which reached the highest maximum concentrations in surface waters in the data reported in the literature. The highest percentages of ecotoxicity data regarding antihypertensives were also related to these beta-blockers. On the other hand, there is clearly a lack of ecotoxicity data, especially the chronic ones, regarding other antihypertensives. The environmental risk assessment (ERA) showed that all three of the evaluated beta-blockers can pose a potential long-term risk for non-target organisms of both fresh and marine water species. However, more meaningful ecotoxicity data for antihypertensives, including saltwater species, are required to refine and enlarge these results. Additional studies focusing on potential interactions between pharmaceutical mixtures, including antihypertensives, are also an urgent need.

Ecotoxicological evaluation of propranolol hydrochloride and losartan potassium to Lemna minor L. (1753) individually and in binary mixtures.

Antihypertensive pharmaceuticals, including the beta-blockers, are one of the most detected therapeutic classes in the environment. The ecotoxicity of propranolol hydrochloride and losartan potassium was evaluated, both individually and combined in a binary mixture, by using the Lemna minor growth inhibition test. The endpoints evaluated in the single-pharmaceutical tests were frond number, total frond area and fresh weight. For the evaluation of the mixture toxicity, the selected endpoint was frond number. Water quality criteria values (WQC) were derived for the protection of freshwater and saltwater pelagic communities regarding the effects induced by propranolol and losartan using ecotoxicological data from the literature, including our data. The risks associated with both pharmaceutical effects on non-target organisms were quantified through the measured environmental concentration (MEC)/predicted-no-effect concentration (PNEC) ratios. For propranolol, the total frond area was the most sensitive endpoint (EC50 = 77.3 mg L(-1)), while for losartan there was no statistically significant difference between the endpoints. Losartan is only slightly more toxic than propranolol. Both concentration addition and independent action models overestimated the mixture toxicity of the pharmaceuticals at all the effect concentration levels evaluated. The joint action of both pharmaceuticals showed an antagonistic interaction to L. minor. Derived WQC assumed lower values for propranolol than for losartan. The MEC/PNEC ratios showed that propranolol may pose a risk for the most sensitive aquatic species, while acceptable risks posed by losartan were estimated for most of aquatic matrices. To the authors knowledge these are the first data about losartan toxicity for L. minor.