10/30/2008

Identification and evaluation of selected pharmaceuticals and their metabolites in the water cycle

German Federal Environment Agency, FZK 206 61 202, project duration 11/2006 - 10/2008

Sponsor

German Federal Environment Agency, Dessau (FKZ 206 61 202)

Realisation

Environmental Medicine and Hospital Epidemiology, Freiburg University, Prof. Dr. Klaus Kümmerer (project management)
Water Technology Center, Karlsruhe, Dr. Carsten Schmidt
FoBIG GmbH, Freiburg, Dr. Klaus Schneider
Hydrotox GmbH, Freiburg, Stefan Gartiser Hydrotox GmbH

Project duration

November 2006 – October 2008

Project description

In this project, all originally applied substances are denoted as active ingredients or mother substances (MS); hence, all substances having undergone modification in the human body are referred to as metabolites (ME) and all subsequently arising products are referred to as transformation products (TP); these may be bacterial TP, abiotic TP or technical TP, resulting for example from drinking water purification. The main focus of the project is whether persisting MS and ME can lead to mutagenic/genotoxic TP if drinking water purification includes an ozonation process. First, we developed a method to identify potentially problematic MS and ME. Next, selected substances were tested in respect of their biodegradability and fate during drinking-water-ozonation. The Ames-test to identify mutagenic activity was performed using the original solutions of the biodegradability tests and the same solutions after ozonation – here we interposed solid-phase extraction (SPE) to concentrate substances before the Ames-test. From a total number of 706 balanced MS, we selected 19 MS known to undergo intensive metabolisation and identified 36 isomeric MS and 84 ME. These 120 substances were screened for their toxicological and environmental relevance. We considered literature as well as QSAR-models, computing the end-points biodegradability, mobility and mutagenicity/genotoxicity. The laboratory study included the ME 4-acetamidoantipyrine, 4-formylaminoantipyrine and sulfapyridine as well as the MS metformin and piracetam, which are excreted without metabolisation. We also ozonated guanylurea, a recently identified dead-end TP of metformin. With the exception of piracetam, all the tested substances were only incompletely biodegradable, suggesting formation of stable bacterial TP. Metformin, piracetam and guanylurea could not be removed completely by the ozonation process. We received some evidence that technical TP are formed by ozonation of metformin and piracetam, whereas all tested ME were completely degraded by this treatment. None of the experiments showed an increase n mutagenicity in the Ames-test. The adequacy and sensitivity of the methodology need to be further investigated.

Further Informationen

The final report (in German) has been published as UBA-Texte 46/2011 and can be downloaded from the UBA website.

Contact person

Dr. Stefan Gartiser
Mail: Gartiser(at)hydrotox.de
Tel: +49-(0)761-45512-24

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