The release of Active Pharmaceutical Ingredients (APIs) to the environment is an issue of increasing importance which takes place for many years now. This happens mainly through the Urban Wastewater Treatment Plants effluents’ discharges in which multi-component mixtures (parent compounds, metabolites and transformation products) of APIs exist.

Because the importance of this diffuse pollution to the aquatic environment is now recognized, the European Medicines Agency has published a guideline on the environmental risk assessment of APIs for human use. Nevertheless, the number of studies dealing with the effects of APIs residues on aquatic organisms and risk assessment is still limited and scarce, particularly regarding long-term studies and only very few studies have observed the effects of mixtures. This issue


constitutes one of the major research gaps in the specific scientific field.

The study of chemical mixtures is limited for a number of reasons. It is much easier to study a single compound in an animal study and to obtain traditional dose – response information. An almost infinite number of combinations of contaminants is possible though, and often we do not know which is most important and environmentally relevant, or which ranges of doses should be investigated, or which biologic endpoints should be studied. Although relatively few studies have investigated the interactions of even two chemicals, in real life we are all exposed to multiple substances (chemical cocktails), and the biological effects of more than 20 different chemicals for example may be very different from those of just two.