ERAPharm - Environmental risk assessment of pharmaceuticals

EC contribution: : € 2.797.198
Duration: : 36 months
Starting date: : 01/10/2004
Funding scheme: : Specific Targeted Research Project
Keywords: : human and veterinary pharmaceuticals, antibiotics
Contract/Grant agreement number: : SSPI-CT-2003-511135
Project web-site: : http://www.erapharm.org/

Background:

Project logo ERAPharm aimed to improve existing knowledge and methods for evaluating potential risks posed by human and veterinary pharmaceuticals to the environment. The consortium addressed the different aspects of environmental risk assessment (ERA) of pharmaceuticals, including exposure modelling as well as effects on microorganisms, aquatic and terrestrial invertebrates and fish. Based on the results of the fate and effect studies, recommendations have been provided on how to improve current European ERA procedures for human and veterinary pharmaceuticals.

ERAPharm has been grouped into eight interdependent Work Packages

Problem:

A large variety of pharmaceuticals is used in the treatment and prevention of diseases. Following administration to humans or animals, these pharmaceuticals are released to the environment mainly via sewage effluents and via application of sewage sludge and manure to land. The widespread detection of pharmaceuticals in surface waters, soils and groundwater worldwide has raised major concerns about the potential impact of these bioactive substances on the environment. European regulatory guidelines for assessing the environmental risks of pharmaceuticals have been established. However, there are still considerable gaps in the current knowledge on fate and effects of pharmaceuticals in the environment, including the occurrence of antibiotic resistance in the environment.

Aim:

The overall aim of ERAPharm is to advance existing knowledge and procedures for the environmental risk assessment of human and veterinary pharmaceuticals. This aim has been addressed by a consortium consisting of 14 partners from six EU member states, one associated state and Canada. ERAPharm has addressed the following aspects:

To investigate previously unstudied major routes leading to exposure of the terrestrial and aquatic environment and factors and processes affecting the subsequent fate of pharmaceuticals in soils, sediments and surface water.
To further develop testing approaches for evaluating the fate of pharmaceuticals.
To develop a scenario-based exposure assessment system for predicting the concentrations of pharmaceuticals in soils, surface water and sediments.
To explore to what extent in vitro and low complexity bioassays can be used to provide a first hazard characterisation and mode-of-action classification.
To investigate whether and to what extent environmentally relevant concentrations of pharmaceuticals cause effects in the environment.
To study the effects of antibiotics on structure and function of microbial communities and on antibiotic resistance in environmental compartments.
To evaluate how information on pharmacodynamics and toxicodynamics in mammals can be used to guide the evaluation of potential sublethal effects in fish.
To modify and refine test methods in order to detect the effects of long-term, low-level exposure to pharmaceuticals.
To provide recommendations on how to improve current European environmental risk assessment procedures for pharmaceuticals.

DGGEs (denaturing gradient gel electrophoresis of 16S rRNA) reveal shifts in bacterial populations in soil after exposure to antibiotics

DGGEs (denaturing gradient gel electrophoresis of 16S rRNA) reveal shifts in bacterial populations in soil after exposure to antibiotics

Expected and obtained results:

Analytical methods were developed and adapted to determine selected pharma-ceuticals in various environmental matrices. In laboratory, semi-field and field studies, data on sorption, partitioning, transformation and biodegradation of human and veterinary pharmaceuticals were generated.
Three new scenarios were identified as being insufficiently covered in the existing framework for the ERA of veterinary pharmaceuticals, despite being relevant for veterinary pharmaceuticals. Existing models to predict physico-chemical properties and fate of pesticides were evaluated and adapted for use with pharmaceuticals.
The effects of a set of human and veterinary pharmaceuticals were studied: (1) in in vitro and low complexity bioassays, and (2) on aquatic and terrestrial organisms, at single species, population and community level using laboratory, micro- and meso-cosm and field studies.
The effects of antibiotics were investigated in terrestrial and aquatic microbial microcosm studies. Structural changes detected at the molecular level were observed at antibiotic concentrations where only slight functional changes were apparent, whereas the potential of antibiotics to increase the level of antibiotic resistance in the test systems appeared to be low, especially at environmentally realistic concentrations.
Recommendations are provided on how to improve existing test strategies and environmental risk assessment procedures for human and veterinary pharmaceuticals.

Potential applications:

Improved modelling and testing methods will contribute to an improved fate and effects assessment of pharmaceuticals, especially at higher tiers of the environmental risk assessment. Overall, the knowledge that is generated by ERAPharm will result in a more accurate assessment of the risks posed by pharmaceutical products to the environment and will provide a better basis to select appropriate risk mitigation measures. ERAPharm is expected to contribute to the establishment of more targeted and more standardised environmental risk assessment procedures for pharmaceuticals.

ERAPharm members have been involved in international committees such as advisory groups of the Society of Environmental Toxicology and Chemistry (SETAC) and Pellston workshops. Advanced test protocols for assessing fate and effects of pharmaceuticals were developed, e.g. within the Organisation for Economic Co-operation and Development (OECD). Specific input was also provided by submitting proposals on improvements of the ERA of pharmaceuticals to working groups of the European Food Safety Authority (EFSA) and the European Medicines Agency (EMEA).

Coordinator:

Dr Thomas Knacker
ECT Oekotoxikologie GmbH
Böttgerstrasse 2-14
65439 Flörsheim/M., Germany
Tel.+49 6145956411
Fax +49 6145956499
th-knacker@ect.de

European Commission