Environmental risk assessment of medicinal products for human use according to European Commission recommendations

Presented here, based on new recommendations of the European Commission, is an environmental risk assessment (ERA) of a selected group of pharmaceuticals for Phase I, environmental exposure assessment, and Phase II Tier A, initial environmental fate and effect analysis. This pharmaceutical group is composed of the 111 highest-selling human drug substances that have annual sales in Germany of more than 5,000 kg. The data required for this ERA came from analyzing: (1) sales annually (in kg or IU) of the 2671 active pharmaceutical drug substances (2001) on the German market in all medicinal products sold by pharmacies (with and without prescriptions) and used in hospitals in 1996-2001; (2) the use pattern of drug substances as categorized according to Anatomical Therapeutic Chemical (ATC) classification indexes ATC3 and ATC7; (3) data for excretion, toxicity, and metabolites of the 111 selected human drug substances; (4) the physicochemical properties of these substances; and (5) the degradability of selected drug substances in sewage treatment plants (STPs) by using a validated and accredited liquid chromatography-electrospray ionization tandem mass spectrometry method. A correction factor for the pharmaceutical therapeutic (PT) activity of metabolites, the PT(Index) (excretion rate/100) for drug substances and PT active metabolites was established to refine the predicted environmental concentration (PEC(SURFACEWATER)). A refinement of the PEC(SURFACEWATER) was carried out with the market penetration factor of the human drug substances in Germany. In addition, for effect analysis the predicted no-effects concentration (PNEC) was calculated using assessment factors. The estimated PEC results were validated with the exposure results of effluents of the STPs. All results on ERA of drug substances have been documented in a Microsoft Access 2000 database.