Biodegradability and transformation of human pharmaceutical active ingredients in environmentally relevant test systems.

Human pharmaceutical active ingredients that are orally or parenterally administered may be metabolised in the body and after excretion may be further transformed in the receiving environmental compartments. The optimal outcome from an environmental point of view-complete mineralisation-is rarely observed. Small molecule pharmaceuticals are commonly not readily biodegradable according to Organisation for Economic Cooperation and Development (OECD) 301 tests. However, primary transformation is often observed. To gain information on the transformation of active ingredients in the environment, long-term studies like transformation in aquatic water/sediment systems according to OECD guideline 308 are required for the environmental risk assessment for human active pharmaceutical ingredients. Studies received until mid 2010 as part of the dossiers for marketing authorisation applications were evaluated concerning transformation products. The evaluation revealed that in 70% of the studies, at least one transformation product (TP) is formed above 10% of the originally applied dose, but in only 26% of the studies are all TP identified. The evaluation also revealed that some TP of pharmaceutical active ingredients show a considerably longer DT50 compared to the parent compound. An example is the TP (val)sartan acid that is formed from an antihypertensive compound.

Identification, assessment and management of "endocrine disruptors" in wildlife in the EU substance legislation--discussion paper from the German Federal Environment Agency (UBA).

A discussion paper was developed by a panel of experts of the German Federal Environment Agency (UBA) contributing to the on-going debate on the identification, assessment and management of endocrine disruptors with a view to protect wildlife according to the EU substance legislation (plant protection products, biocides, industrial chemicals). Based on a critical synthesis of the state-of-the-art regarding regulatory requirements, testing methods, assessment schemes, decision-making criteria and risk management options, we advise an appropriate and consistent implementation of this important subject into existing chemicals legislation in Europe. Our proposal for a balanced risk management of endocrine disruptors essentially advocates transparent regulatory decision making based on a scientifically robust weight of evidence approach and an adequate risk management consistent across different legislations. With respect to the latter, a more explicit consideration of the principle of proportionality of regulatory decision making and socio-economic benefits in the on-going debate is further encouraged.