Suchergebnisse

AbstractHuman pharmaceuticals are extensively studied and assessed before marketing approval. Since 2006, this also includes an assessment of environmental risks. In the European Union, this is based on the guideline on the environmental risk assessment of medicinal products for human use (EMEA/CHMP/SWP/4447/00 corr 2), which is currently under revision. For Germany, the German Environment Agency (UBA) is tasked with the evaluation of environmental risks of human pharmaceuticals. Applicants seeking approval of medicinal products need to submit fate and effect data, in case predicted environmental concentrations (PECs) exceed 10 ng/L in surface waters, or the substance is of specific concern through its mode of action or physico-chemical characteristics.Over the last decade, this regulatory work resulted in an internal agency database containing effect data on approximately 300 active pharmaceutical ingredients (APIs). A considerable part of this data is currently not publicly available due to property rights held by the respective applicants. The database was evaluated to draw conclusions on how the current assessment approach may be improved.The evaluation of aquatic effect data shows considerable variation in ecotoxic effect concentrations, but supports the current use of 10 ng/L as PEC action limit. For endocrine-active substances and antibiotics, a clear sensitivity profile was observed, which allows a more targeted assessment in the future. The conclusions drawn from terrestrial effect data are less clear, as the database itself is biased because information is only available for substances with high sorption. Further adaptations of the terrestrial assessment strategy, including action triggers, appear necessary. Fate data show a high persistence of many APIs: approximately 43% of all APIs are classified as very persistent; 12% of these show DT50 values in a range where abiotic or biotic degradation is not expected.Overall, the evaluation has shown that improvements of the current guideline are possible.

Endocrine active therapeutics such as steroid hormones gain increasing focus in environmental research as it was reported that they cause endocrine disruption in aquatic organisms exposed to environmentally relevant concentrations. Data about occurrence and fate of steroid hormones are scare. In this study occurrence of about 60 steroids in wastewater treatment plant effluents and surface waters as well as the fate and biodegradability of corticosteroids and progestogens in activated sludge treatment were investigated. Corticosteroids and progestogens were prioritized in views of their high prescription and potency to impact endocrine-related functions. A reliable analytical method for the simultaneous determination of mineralocorticoids, glucocorticoids and progestogens in the aquatic environment was developed. Utilizing this method three mineralocorticoids, 23 glucocorticoids and 10 progestogens could be detected in the analyzed samples, many of them were detected for the first time in the environment, particularly in Germany and the EU. Moreover, biodegradation studies were designed to enable the comparison of the biodegradability and transformation processes in activated sludge treatment for structure-related steroids under standardized aerobic conditions. Half-lives ranged from 14 d suggesting large variations in the biodegradability. Transformations products were identified by LC-HRMS and transformation pathways were proposed. Based on these data relationships between structure and stability were elaborated. Several of the newly identified transformation products were persistent and some of them could be detected in wastewater treatment plant effluents and surface waters. Hence, these transformation products should be also included in environmental monitoring.

Since the last decades the increasing detections of pharmaceuticals in the aquatic environment and their risk potential for the aquatic life have become an urgent issue. Even though many pharmaceuticals are at least to some extent removed by sorption and biotransformation during conventional wastewater treatment, a quasi continues emission via wastewater treatment plants result in a so called "pseudo-persistence". Furthermore, metabolites and transformation products (TPs) can show comparable or even higher activities. Therefore, a higher prioritization of pharmaceuticals and their metabolites as well as TPs as environmental pollutants in the European Water Framework Directive and German surface waters regulation (Oberflächengewässerverordnung) would be desirable. Determination of pharmaceuticals in the aquatic environment is focused on the liquid phase. However, only a few standardized methods exist. Indeed, physicochemical parameters of some analytes let accumulation in sediment, suspended particular matter and biota seem to be likely. Hence, these matrices could be interesting alternative matrices for monitoring of pharmaceutical residues in surface waters. The aim of this project was the development, optimization, validation and benchmarking of analytical methods for quantification of selected active pharmaceutical ingredients, their metabolites and TPs in different environmental matrices (water, sediment, suspended particular matter and biota). Using these methods occurrence and distribution of the selected analytes in water, sediment, suspended particular matter and biota samples from different locations were determined. Additionally, samples from the German environmental specimen bank were analyzed to investigate possible time trends in concentrations of pharmaceuticals and to demonstrate the potential of the new methods. Finally, recommendations regarding optimal strategies for determination of pharmaceutical residues with different physicochemical properties in water systems were derived from during this project obtained new insights.

In preparation of the revision of Directive 2001/83/ EC and Regulation (EC) No 726/2004, the German Environment Agency (⁠UBA⁠) proposes legal changes to reduce pharmaceutical residues in the environment. The proposals are based on UBA's experiences as competent authority for the environmental risk assessment (ERA) of pharmaceuticals. Our overall aim is to ensure a comprehensive risk management system without compromising availability of medicines for patients. In this context we consider the recent EU strategy on pharmaceuticals and initiatives in connection with EU`s Green Deal particularly the Zero Pollution Ambition and the one substance one assessment approach.

Since the last decades the increasing currency of pharmaceuticals in the aquatic environment and their risk potential for the aquatic life has become an urgent issue. The number of pharmaceuticals detectable in the low μg/L range in the environment is rising each day. Against this background the aim of this project was the development, optimization, validation and comparison of analytical methods for quantification of selected pharmaceuticals in different environmental matrices (water, sediment, suspended particular matter and biota). High sensitive LC-MS-MS methods for determination of extreme polar, polar and hormonal pharmaceuticals in water samples were developed and validated. Using these methods occurrence and distribution of the selected pharmaceuticals in water with different waste water content were determined. For analysis of pharmaceuticals in particular matter and biota samples extraction and clean-up procedures were tested, but method development is still in process. Furthermore a monitoring campaign was set up and water samples, suspended particular matter and biota (fish) samples from six different sampling sites were taken.

Derzeit ist das Wissen um den Verbleib von Arzneimittelrückständen in der Umwelt und deren negativen Umweltauswirkungen vielen Personen aus Fachkreisen im Gesundheitswesen kaum bekannt bzw. in Lehre, Fort- und Weiterbildungen nur rudimentär enthalten. Durch ihren vielschichtigen Kontakt mit Patienten*Patientinnen sind Apotheker- und Ärzteschaft als wichtige Multiplikatoren in der Lage, im direkten Kontakt Fachwissen an Patienten*Patientinnen und Kunden*Kundinnen weiterzugeben. Ein verbessertes Wissen zu dieser Thematik kann es sowohl Apotheker*innen und Ärzteschaft als auch Patienten*Patientinnen ermöglichen, ihr Verhalten bei Verschreibung, Verbrauch und Entsorgung von Medikamenten umweltfreundlicher zu gestalten. Dieser Bericht stellt einen Arbeitsplan für die Verankerung der Thematik Arzneimittelrückstände in der Umwelt in der Lehre medizinischer und pharmazeutischer Berufe in Deutschland vor. Er liefert zuerst eine Bestandsaufnahme der relevanten Strukturen in Lehre und Ausbildung medizinischer und pharmazeutischer Berufe. In einem zweiten Schritt listet er konkrete Empfehlungen zur Integration der Thematik in Lehre (Studium und Ausbildung), Fort- und Weiterbildungen wie auch zur Verbreitung der Inhalte und der im Projekt zu entwickelnden Lehrmaterialien auf.

Übergeordnetes Ziel des Vorhabens "Umwelteinträge von Arzneimittelwirkstoffen – Bilanzierung der Emissionen sowie Konsequenzen für Risikobewertung und -management" ist, Eintragsquellen von Arzneimittelwirkstoffen realistisch einschätzen und so die gültigen Expositionsverfahren überprüfen zu können. Die Ergebnisse sollen insbesondere in Berechnungsmodelle neuer Eintragspfade einfließen, um so eine bessere Umweltfolgenabschätzung zu ermöglichen - entsprechend des strategischen Ansatzes der Europäischen Kommission zu Arzneistoffen in der Umwelt. Die erforderlichen Daten sollen über Erhebungen gewonnen werden. Auf Basis der hierdurch gewonnenen Erkenntnisse können Strategien zur Verminderung von Arzneistoffeinträgen in die Umwelt konkretisiert werden. Im Fokus des Vorhabens stehen Arzneistoffverbräuche bei Lebensmittel liefernden Tieren, bei Nicht-Lebensmittel liefernden Tieren sowie wichtige emissionsrelevante Angaben von Arzneimittelproduktionsstandorten in Deutschland. In Teilvorhaben I, Konzepterstellung der Befragungen, werden für eine entsprechend notwendige Erhebung sinnvolle Konzepte beschrieben, mit deren Ergebnissen die Emissionen aus den drei genannten Bereichen in Deutschland besser abgeschätzt werden können. Auf Basis der erarbeiteten Konzepte zur Erhebung von Umwelteinträgen durch Tierarzneimittel und Arzneistoffproduktionsstandorte sind nachfolgend konkrete Erhebungen, Auswertungen und Strategiekonzepte zur Stoffeintragsreduktion durchzuführen. Die Erhebungskonzepte umfassen, je nach Fokus, interviewgestützte Erhebungen in ausgewählten repräsentativen Landkreisen, eine Befragung von Privathaushalten sowie Datenerhebungen bei Herstellern.

Parasiticides are veterinary pharmaceuticals very frequently used in pasture animals. Particularly substances of the classes of avermectins and milbemycins are very common. These substances are highly toxic to non-target organisms, often stable in the environment (persistent) and may potentially accumulative in organisms. The present project contributes to filling environmental data gaps for avermectins and milbemycins. In addition, risk management strategies for parasiticides used in pasture animals were evaluated with regard to their efficacy and practicability reducing the risk to dung or soil organisms.