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

Abstract

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.

Fingerprinting groundwater pollution in catchments with contrasting contaminant sources using microorganic compounds

“…Because of the vast number of compounds, many studies have selected determinands according to priority lists taking into account consumption and predicted environmental concentrations as well as ecotoxicological, pharmacological and physicochemical data (Besse and Garric, 2008;Celiz et al, 2009;Crane et al, 2008;Fent et al, 2006;Hilton et al, 2003;Huschek et al, 2004). A systematic review of emerging contaminants in groundwater, by Lapworth et al (2012) highlighted the widespread contamination of resources worldwide.…”

Emerging organic contaminants in groundwater: A review of sources, fate and occurrence

“…Because of the vast array of possible compounds, many studies have selected EOCs according to priority lists established taking into account consumption, predicted environmental concentrations as well as ecotoxicological, pharmacological and physicochemical data (e.g. Hilton et al, 2003;Huschek et al, 2004;Fent et al, 2006;Crane et al, 2006;Besse and Garric, 2008;Celiz et al, 2009). …”

Ecotoxicological Classification of the Berlin River System Using Bioassays in Respect to the European Water Framework Directive

“…50-70 substances present. Beside the drug substances (Huschek et al, 2004) several polyaromatic substances are present in the River Havel sediments. In the Havel River sediments there were Tributyl-Sn (TBT) concentrations in the range of 1.600 ng/g oven-dry mass detected.…”

“…Beside the load of sediments by EDC there are several active drug substances used in large quantities for humans and livestock in industrialised countries, see Table III which have been frequently found in sewage treatment plants (STPs), in the surface waters (Huschek et al, 2004) and finally also TABLE II Selected biochemical responses for the assessment of environmental health of organisms and the biomarker methods used for their examination (Bresler et al, 1999) Method…”