Pharmaceuticals in the environment--Global occurrences and perspectives.

Pharmaceuticals are known to occur widely in the environment of industrialized countries. In developing countries, more monitoring results have recently become available, but a concise picture of measured environmental concentrations (MECs) is still elusive. Through a comprehensive literature review of 1016 original publications and 150 review articles, the authors collected MECs for human and veterinary pharmaceutical substances reported worldwide in surface water, groundwater, tap/drinking water, manure, soil, and other environmental matrices in a comprehensive database. Due to the heterogeneity of the data sources, a simplified data quality assessment was conducted. The database reveals that pharmaceuticals or their transformation products have been detected in the environment of 71 countries covering all continents. These countries were then grouped into the 5 regions recognized by the United Nations (UN). In total, 631 different pharmaceutical substances were found at MECs above the detection limit of the respective analytical methods employed, revealing distinct regional patterns. Sixteen substances were detected in each of the 5 UN regions. For example, the anti-inflammatory drug diclofenac has been detected in environmental matrices in 50 countries, and concentrations found in several locations exceeded predicted no-effect concentrations. Urban wastewater seems to be the dominant emission pathway for pharmaceuticals globally, although emissions from industrial production, hospitals, agriculture, and aquaculture are important locally. The authors conclude that pharmaceuticals are a global challenge calling for multistakeholder approaches to prevent, reduce, and manage their entry into and presence in the environment, such as those being discussed under the Strategic Approach to International Chemicals Management, a UN Environment Program.

Pharmaceuticals and personal care products in the environment: what are the big questions?

BACKGROUND: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. OBJECTIVE: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. DATA SOURCES: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. DATA SYNTHESIS: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f ) antibiotic resistance, and g) risk management. CONCLUSIONS: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.

Highly active human pharmaceuticals in aquatic systems: A concept for their identification based on their mode of action.

Widespread occurrence of traces of pharmaceuticals (ng/L to microg/L) has been reported in aquatic systems. However, their effects on the environment and their environmental risks remain elusive. Generally, the acute toxicity towards non-target organisms has been assessed in laboratory experiments, but chronic toxicity studies have been performed only rarely. The guideline issued by the European Medicines Agency in 2006 is aimed at estimating the potential environmental risks of human pharmaceuticals by a tiered approach. The predicted environmental concentration (PEC) of a compound is estimated in phase I, and pharmaceuticals having a PEC above or equal 10ng/L undergo phase II testing. Otherwise they are not expected to pose a risk to the environment. Because some highly active compounds (HC) such as 17-alpha-ethinylestradiol, equine estrogens, trenbolone and the progestin levonorgestrel display adverse effects at concentrations below 10ng/L the question arises, whether additional HC compounds exist, and how they can be identified for undergoing environmental risk assessment. We addressed this question by searching for HC in the literature, and by developing a concept for identification of HC. The suggested mode of action concept is based on (i) the mode of action of the pharmaceutical taking the available toxicological information into account, (ii) the degree of sequence homology between the human drug target and the potential target in aquatic organisms and (iii) the importance of pathways affected by the pharmaceutical. We evaluated the mode of action concept by comparison to existing approaches, the fish plasma model (Huggett et al., 2003) and a QSAR model, called VirtualTox Lab (www.biograf.ch). All concepts result in similar classifications of the selected pharmaceuticals. However, there are some differences not only in the model assumptions, but also in its results. Our study leads to the conclusion that the mode of action concept is most suitable for the identification of HC. A refinement can be achieved by complementing this concept by the QSAR model (VirtualTox Lab), whereas the fish plasma model seemed to be less suitable due to the necessity of environmental concentration above 10ng/L for the identification of a risk.