Environmental risk assessment of human pharmaceuticals in the European Union: A case study with the β‐blocker atenolol

Abstract

β-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 characterized in fish and other aquatic animals, so it can be expected that physiological processes regulated by these receptors in wild animals may be affected by the presence of β-blockers. Because 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. A 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, for 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 2-generation reproduction test with the waterflea Daphnia magna resulted in the most sensitive no-observed-effect concentration (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. 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 physicochemical characteristics and varying toxicological profiles in mammalian studies.

Comparative metabolism as a key driver of wildlife species sensitivity to human and veterinary pharmaceuticals

“…In some cases, however, environmental exposures of wildlife to pharmaceutical residues can have dramatic consequences on non-mammalian species, as seen in the case of diclofenac and vultures [56][57][58] or fish populations in ecosystems exposed to synthetic oestrogens [71] (also see [72]). These notable examples, together with evidence of the widespread presence of pharmaceuticals in the environment, have been widely recognized to support the need for predictive environmental risk assessments [73][74][75][76] and consideration of the API residues in cattle and other livestock species [77].…”

“…Specifically, together with prioritization through the predicted exposure concentration approach, an understanding of ADMET can play an important role in defining and predicting no-observed effect concentrations for freshwater, terrestrial and other environmental compartments, including predators [74,75,85]. In addition to this predictive aspect of pharmaceutical risk assessment, an understanding of ADMET can provide an important role for targeted monitoring of wildlife species of concern (e.g.…”

A farewell to Dr Thomas Knacker (* 29.04.1951 – † 30.10.2011): scientific contributions and personal memories

“…Recently, Thomas focused his activities on the outcome of the ERAPharm project [19][20][21][22][23]. Thomas Knacker dedicated most of his professional life to the science of ecotoxicology.…”

Role of organic matter, clay, and iron contents in the sorption of oxytetracycline on river sediments

“…Studies have shown that a large percentage of consumed antibiotics is excreted without change (2) into the hydrosphere. Many researchers have detected various antibiotics in water samples (3). Sewage treatment plants do not remove residual antibiotics from wastewater (4), and this contributes to the risk of new generations of bacteria with modified resistance to antibiotics being created (5,6).…”