Press Release

Press release: The EC-FP7 funded project Fate and effects of cytostatic pharmaceuticals in the environment and identification of biomarkers for an improved risk assessment on environmental exposure (CytoThreat - FP7-ENV-2010, No. 265264)

Submited by CytoThreat Consortium - http://www.cytothreat.eu/

 

press release fig01

 

"This project received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n. 265264"

 

Anticancer drugs in the aquatic environment: sources and effects

The development of pharmaceuticals together with the progress of modern medicine brought enormous benefits to humans in terms of healthier and longer lives. It is estimated that in Europe more than 3000 different pharmaceuticals are in use which represents consumption of around 100 000 tons per year. Part of these compounds is released to the aquatic environment predominantly through patients' excretion either in form of the parent drugs or as metabolites. The crucial question is what happens to pharmaceuticals after they have been used. Are they degraded in wastewater treatment plants? Do active forms reach rivers and drinking water? What are the concentrations and do they affect aquatic organisms or even human health? A group of pharmaceuticals which is of particular concern are anticancer drugs, also termed as cytostatics or antineoplastics, that are used for treatment of cancer. These drugs have been designed to kill cancer cells, for example by interfering with the genetic material and the processes governing their replication. However, these effects are not restricted to cancer cells because the organisation of genetic material as well as the mechanisms of cell replication remained through the evolution highly conserved and are thus similar in different organisms. Therefore, if present in the aquatic environment, the residues of these compounds can potentially harm aquatic organisms in particular during the expected chronic exposure.

The EC-FP7 funded project CytoThreat focuses on the evaluation of the environment and human health risks posed by cytostatic pharmaceuticals released into aquatic environment. The researchers make use of advanced both chemical and biological techniques to assess the presence and distribution of selected cytostatics and their degradation products in the ecosystem as well as their adverse effects as single compounds and in mixtures to aquatic organisms and to human cell lines. Based on consumption data and simple modelling they predicted cytostatics environmental concentrations and thus identified the compounds most likely to occur in the aquatic environment. For determination of these compounds in the water cycle the analytical groups participating in Cytothreat have developed different high sensitivity methodologies, and among them a fully automated method based on on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS. These methodologies are capable of detecting the targeted cytostatic pharmaceuticals, metabolites and transformation products at the very low concentrations at which they can be present (and eventually active) in the aquatic environment. These methods are currently being used to determine their occurrence, distribution and fate in wastewaters and surface waters and to see whether the predicted concentrations conform with the levels measured in real samples.

In the course of the project four compounds belonging to different groups of cytostatics (the antimetabolite 5-fluorouracil; the metal based alkylating agent cisplatin, the topoisomerase inhibitor etoposide, and the tyrosin kinase inhibitor imatinib mesilate) were selected for comprehensive toxicological studies in aquatic organisms from various trophic levels, including algae, bacteria, crustaceans, mussels, higher plants and zebrafish (representing the vertebrates). The results indicated distinct differences in the sensitivity both, among the species and with respect to the tested cytostatic compounds. Of particular concern is chronic exposure as adverse effects of certain compounds were observed at concentrations which are close to those detected in waste waters. In addition, all four compounds caused in crustacea, mussel and higher plants DNA damage. It is known that the release of compounds which affect the integrity of genetic material can affect the fertility of wild species – and may lead to adverse effects in ecosystems. To explore which processes are affected during the chronic exposure the researches applied state-of the art toxicogenomic analysis. In zebrafish exposed to 5-fluorouracil through two generations changes in expression of different genes at very low exposure concentrations were observed and these data are now being used to try to identify early markers of the effects of chronic exposure. These parameters may be used for early prediction of delayed effects in further studies with other compounds, their metabolites, degradation products, and mixtures of them.

The project, which has been running for two and a half years now, is conducted by a highly inter-disciplinary group with partners form Slovenia, Spain, Italy, Austria, Hungary, Croatia and Serbia. By the end of the project in 2014 it is expected that the obtained results will fill important knowledge gaps regarding the adverse effects of cytostatics to aquatic organisms. In addition, the determination of the concentrations and of the distribution of these hazardous compounds in the aqueous environment may have important impact on water quality management programmes. Taken together, Cytothreat is expected to play a major role in safeguarding the public from toxic pharmaceuticals and their by-products.