TY - JOUR
T1 - Environmental risk assessment of human pharmaceuticals in the European union
T2 - A case study with the β-blocker atenolol
AU - Küster, Anette
AU - Alder, Alfredo C.
AU - Escher, Beate I.
AU - Duis, Karen
AU - Fenner, Kathrin
AU - Garric, Jeanne
AU - Hutchinson, Thomas H.
AU - Lapen, David R.
AU - Péry, Alexandre
AU - Römbke, Jörg
AU - Snape, Jason
AU - Ternes, Thomas
AU - Topp, Ed
AU - Wehrhan, Anne
AU - Knackerk, Thomas
PY - 2010/7
Y1 - 2010/7
N2 - β-Adrenergic receptor blockers (b-blockers) are applied to treat high blood pressure, ischemic heart disease, and heart rhythm disturbances. Due to their widespread use and limited human metabolism, b-blockers are widely detected in sewage effluents and surface waters. b-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 bblockers. Because ecotoxicological data on b-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 forhumanuse. 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 KOW0.16), a low potential for exposure of the terrestrial compartment via sludge (log KOC2.17), 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. A2-generation reproduction test with the waterflea Daphnia magna resulted in the most sensitive no-observed-effect concentration (NOEC) of 1.8mg 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 b-blockers, such as metoprolol, oxprenolol, and propranolol, some of which show significantly different physicochemical characteristics and varying toxicological profiles in mammalian studies. Integr Environ Assess Manag 2010;6:514523.
AB - β-Adrenergic receptor blockers (b-blockers) are applied to treat high blood pressure, ischemic heart disease, and heart rhythm disturbances. Due to their widespread use and limited human metabolism, b-blockers are widely detected in sewage effluents and surface waters. b-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 bblockers. Because ecotoxicological data on b-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 forhumanuse. 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 KOW0.16), a low potential for exposure of the terrestrial compartment via sludge (log KOC2.17), 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. A2-generation reproduction test with the waterflea Daphnia magna resulted in the most sensitive no-observed-effect concentration (NOEC) of 1.8mg 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 b-blockers, such as metoprolol, oxprenolol, and propranolol, some of which show significantly different physicochemical characteristics and varying toxicological profiles in mammalian studies. Integr Environ Assess Manag 2010;6:514523.
KW - β-Blocker
KW - Atenolol
KW - Environmental risk assessment
KW - Human pharmaceutical
UR - http://www.scopus.com/inward/record.url?scp=77956372587&partnerID=8YFLogxK
U2 - 10.1897/IEAM-2009-050.1
DO - 10.1897/IEAM-2009-050.1
M3 - Article
C2 - 19886730
AN - SCOPUS:77956372587
SN - 1551-3793
VL - 6
SP - 514
EP - 523
JO - Integrated Environmental Assessment and Management
JF - Integrated Environmental Assessment and Management
IS - SUPPL. 1
ER -