Environmental Risk Assessment of Human Pharmaceuticals in the European Union: A Case Study with the beta-blocker Atenolol - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Article Dans Une Revue Integrated Environmental Assessment and Management Année : 2010

Environmental Risk Assessment of Human Pharmaceuticals in the European Union: A Case Study with the beta-blocker Atenolol

Evaluation du risque environnemental des substances pharmaceutique dans l'Union Européenne : étude du cas du beta-bloquant Atenolol

Résumé

Beta-adrenergic receptor blockers (β-blockers) are applied to treat high blood pressure, ischemic heart disease and heart rhythm disturbances. Due to their widespread use and limited human metabolism β-blockers are widely detected in sewage effluents and surface waters. β-adrenergic receptors have been characterised in fish and other aquatic animals and, therefore, it can be expected that physiological processes regulated by these receptors in wild animals may be affected by the presence of β-blockers. As ecotoxicological data on β-blockers are scarce, it was decided to choose the β-blocker atenolol as a case study pharmaceutical within the project ERAPharm. Starting point for the assessment of potential environmental risks was the European guideline on the environmental risk assessment of medicinal products for human use. In Phase I of the risk assessment, the initial predicted environmental concentration (PEC) of atenolol in surface water (500 ng L-1) exceeded the action limit of 10 ng L-1. Thus, a phase II risk assessment was conducted showing acceptable risks for surface water, groundwater and for aquatic microorganisms. Furthermore, atenolol showed a low potential for bioaccumulation as indicated by its low lipophilicity (log Kow = 0.16), a low potential for exposure of the terrestrial compartment via sludge (log Koc = 2.17) and a low affinity for sorption to the sediment. Thus, the risk assessment according to Phase II-Tier A did not reveal any unacceptable risk for atenolol. Beyond the requirements of the guideline, additional data on effects and fate were generated within ERAPharm. A two-generation reproduction test with the waterflea Daphnia magna resulted in the most sensitive NOEC of 1.8 mg L-1. However, even with this NOEC a risk quotient of 0.003 was calculated, which is still well below the risk threshold limit of 1. The additional studies confirm the outcome of the environmental risk assessment according to EMEA/CHMP (2006). However, atenolol should not be considered as representative for other β-blockers, such as metoprolol, oxprenolol and propranolol some of which show significantly different physico-chemical characteristics and varying toxicological profiles in mammalian studies.
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Dates et versions

hal-02594488 , version 1 (15-05-2020)

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Citer

Alice Kuster, A.C. Alder, B. Escher, K. Duis, Kathrin Fenner, et al.. Environmental Risk Assessment of Human Pharmaceuticals in the European Union: A Case Study with the beta-blocker Atenolol. Integrated Environmental Assessment and Management, 2010, 6 (Suppl. 1), pp.514-532. ⟨10.1897/IEAM-2009-050.1⟩. ⟨hal-02594488⟩

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