CytoThreat addresses the need to assess the risks of pharmaceuticals released in the environment, focusing on cytostatic drugs because they are highly hazardous compounds due to their genotoxic properties which may cause unexpected long term effects. Their release in the environment may lead to systemic ecological effects and increased cancer incidence, reduced fertility and malformations in the offspring in humans. The occurrence, distribution and fate of selected widely used cytostatics in different aquatic matrices, their acute and chronic toxicity and impact on the stability of the genetic material in a variety of aquatic organisms representing different trophic levels is addressed to provide data sets necessary for scientifically based risk assessment. Special emphasis is put on the combined effects of environmentally relevant mixtures. A combination of state-of-the art analytical chemistry, in vivo and in vitro systems, and ‘OMICS’ technologies is applied. In vivo studies with zebrafish models aim at identifying linkages between the genomic profiles, exposure conditions and adverse effects in vertebrates to identify molecular biomarkers for adverse effects of specific groups of cytostatics to be used as diagnostic markers and for predicting synergistic effects of combined exposures. Comparative in vitro genotoxicity and transcriptomic studies with zebrafish and human derived cells will provide additional information for the extrapolation of toxicological data to humans. Comparisons with the hazardous effects of other groups of pharmaceuticals will provide knowledge on the magnitude of the problem. CytoThreat will generate new knowledge on environmental and health risks of cytostatics and provide objective arguments for recommendations and regulations. Partners form 5 member states and 2 associated countries with complementary expertise in analytical chemistry, aquatic and genetic toxicology, and genomics and bioinformatics are involved.
1. To develop new analytical methods for assessment of the occurrence and fate of cytostatic pharmaceuticals, their metabolites and transformation products in water treatment systems and in the environment.
2. To explore potential delayed and irreversible effects of cytostatic pharmaceuticals at environmentally relevant concentrations in aquatic experimental models, and compare the data to those obtained in human experimental models.
3. To explore combined effects of mixtures of cytostatic pharmaceuticals, their excreted metabolites and transformation products formed in the environment and/or waste water treatment.
4. To develop, based on the obtained results, guidance on how to improve the environmental and human risk assessment of cytostatics released into the environment.