Final Report Summary - ERAPHARM (Environmental risk assessment of pharmaceuticals)
The ultimate aim of the ERAPHARM project was to further advance the existing knowledge and procedures for the Environmental risk assessment (ERA) of human and veterinary pharmaceuticals. The specific objectives of the project were to:
- investigate previously unexplored major exposure routes of pharmaceuticals in the terrestrial and aquatic environment;
- investigate factors and processes affecting the fate of pharmaceuticals in soils, sediments and surface water;
- develop a scenario-based exposure assessment system for pharmaceuticals;
- explore the use of bioassays for an initial hazard screening and mode-of-action classification;
- evaluate how information on pharmacodynamics and toxicodynamics in mammals could be used to guide the evaluation of effects on organisms in the environment;
- modify and refine test methods in order to detect the effects of long-term, low-level exposure to pharmaceuticals on aquatic and terrestrial organisms;
- investigate whether and to what extent environmentally relevant concentrations of selected pharmaceuticals cause effects in environmental organisms;
- develop pragmatic approaches for assessing transformation products;
- provide recommendations on how to improve current European environmental risk assessment procedures for pharmaceuticals.
The work addressing the specific objectives of ERAPHARM mainly focused on how to target the ERA by using information from mammalian studies and higher-tier test approaches, how to better assess, model and consider partition and persistence of pharmaceuticals in the environment. Furthermore, it proposed improvements on how to identify pharmaceuticals likely to pose a high risk and use alternative endpoints in the ERA, as well as how to identify transformation products and assess their effects and exposure.
Fate and exposure of human and veterinary pharmaceuticals were investigated by using methods of analytical chemistry for both radio-labelled and non-labelled compounds, and modelling approaches. For selected pharmaceuticals, analytical methods were developed and adapted for various environmental matrices, i.e. water, soil, sediment, dung, manure, invertebrate tissue, and fish plasma, and were validated by inter-laboratory comparison studies for surface water, sediment, wastewater and soil. The established methods were used to study sorption, partitioning, transformation and biodegradation at the laboratory scale with water, marine and freshwater sediments, soil and sludge. Based on these results, recommendations were proposed on how to improve current standard guidelines for the fate assessment of pharmaceuticals.
To explore methods for an initial hazard screening of pharmaceuticals, various v-blockers and parasiticides were tested in a mode-of-action based battery of bioassays which included estimation of baseline toxicity, uncoupling of energy transduction, specific effects on photosynthesis, estrogenic and androgenic activity, reactive toxicity and genotoxicity. To explore effects on bacterial communities and potential development of resistance due to low-level long-term exposure, methods to perform both terrestrial and aquatic microbial microcosm studies were established and applied to test antibiotics from different structural classes.
A scientific opinion paper was prepared which summarised in a concise way the recommendations regarding the ERA of pharmaceuticals. A targeted ERA of pharmaceuticals was proposed by pursuing the same principles as for already established ERAs (e.g. risk characterisation by comparing compartment specific exposure and effects) but by taking advantage of the available non-environmental data and the specific properties of pharmaceuticals such as the biologically active substances. Furthermore, a potential scheme for assessing the risks of transformation products in a timely and cost-effective manner was developed.
- investigate previously unexplored major exposure routes of pharmaceuticals in the terrestrial and aquatic environment;
- investigate factors and processes affecting the fate of pharmaceuticals in soils, sediments and surface water;
- develop a scenario-based exposure assessment system for pharmaceuticals;
- explore the use of bioassays for an initial hazard screening and mode-of-action classification;
- evaluate how information on pharmacodynamics and toxicodynamics in mammals could be used to guide the evaluation of effects on organisms in the environment;
- modify and refine test methods in order to detect the effects of long-term, low-level exposure to pharmaceuticals on aquatic and terrestrial organisms;
- investigate whether and to what extent environmentally relevant concentrations of selected pharmaceuticals cause effects in environmental organisms;
- develop pragmatic approaches for assessing transformation products;
- provide recommendations on how to improve current European environmental risk assessment procedures for pharmaceuticals.
The work addressing the specific objectives of ERAPHARM mainly focused on how to target the ERA by using information from mammalian studies and higher-tier test approaches, how to better assess, model and consider partition and persistence of pharmaceuticals in the environment. Furthermore, it proposed improvements on how to identify pharmaceuticals likely to pose a high risk and use alternative endpoints in the ERA, as well as how to identify transformation products and assess their effects and exposure.
Fate and exposure of human and veterinary pharmaceuticals were investigated by using methods of analytical chemistry for both radio-labelled and non-labelled compounds, and modelling approaches. For selected pharmaceuticals, analytical methods were developed and adapted for various environmental matrices, i.e. water, soil, sediment, dung, manure, invertebrate tissue, and fish plasma, and were validated by inter-laboratory comparison studies for surface water, sediment, wastewater and soil. The established methods were used to study sorption, partitioning, transformation and biodegradation at the laboratory scale with water, marine and freshwater sediments, soil and sludge. Based on these results, recommendations were proposed on how to improve current standard guidelines for the fate assessment of pharmaceuticals.
To explore methods for an initial hazard screening of pharmaceuticals, various v-blockers and parasiticides were tested in a mode-of-action based battery of bioassays which included estimation of baseline toxicity, uncoupling of energy transduction, specific effects on photosynthesis, estrogenic and androgenic activity, reactive toxicity and genotoxicity. To explore effects on bacterial communities and potential development of resistance due to low-level long-term exposure, methods to perform both terrestrial and aquatic microbial microcosm studies were established and applied to test antibiotics from different structural classes.
A scientific opinion paper was prepared which summarised in a concise way the recommendations regarding the ERA of pharmaceuticals. A targeted ERA of pharmaceuticals was proposed by pursuing the same principles as for already established ERAs (e.g. risk characterisation by comparing compartment specific exposure and effects) but by taking advantage of the available non-environmental data and the specific properties of pharmaceuticals such as the biologically active substances. Furthermore, a potential scheme for assessing the risks of transformation products in a timely and cost-effective manner was developed.
