Use of hazard assessment tools of increasing level of complexity for 2 pharmaceuticals : biological and ecological relevance

Alice James (1) , Anis Amara (1) , Rémy Beaudouin (1) , Anne Bado-Nilles (1, 2) , Gaëlle Daniele , Emmanuelle Vulliet , Olivier Palluel (1, 2) , Alain Geffard (2) , Jean-Marc Porcher (1, 2) , Sandrine Andres (1)

1 INERIS - Institut National de l'Environnement Industriel et des Risques
2 SEBIO - Stress Environnementaux et BIOsurveillance des milieux aquatiques

Use of pharmaceuticals and their subsequent indirect emissions as unchanged parent, metabolized drugs or degradation products in aquatic ecosystems implies to increase the scientific knowledge on their likely ecotoxicological impacts and the improvement of the tools to assess them. This is the goal of the DOREMIPHARM project, which aims at developing robust hazard assessment tools for pharmaceutical substances. As these substances are biologically active and might be persistent, toxic effects on organisms are suspected at low concentrations. The project involves different partners and their corresponding skills in order to implement a large number of tools allowing the testing of various scales of experimentation (in vitro, ex vivo, in vivo and mesocosms study) and different level of biological responses. In order to assess whether the current regulatory requirements were sufficient to assess the ecotoxicity of pharmaceuticals, conventional and non conventional endpoints (from a regulatory viewpoint) were tested. The aim of this work is to give an overview of the possible levels of assessment that may be taken on board for environmental hazard assessment of pharmaceuticals, focusing on the work done on diclofenac sodium and carbamazepine. Traditional and regulatory Predicted No Effect Concentrations (PNECs) based on the so-called “conventional” endpoints such as mortality and sublethal endpoints (e.g. growth, reproduction, development) were calculated. These values are derived from standardised laboratory tests on 3 trophic levels: primary producers (algae), primary consumer (invertebrates) and secondary consumers (fish). They were used to compare how the inclusion of less conventional endpoints may drive differently the hazard assessment. These endpoints depict different complexity scales as regards space (laboratory versus mesocosm data) and as regards biological organisation (community, population, individuals, cellular, histological findings, biochemical responses, including immunotoxicity and endocrine activity). It is shown that the concentrations at which effects occur cover several orders of magnitude. Applying this methodology, the so-called early-warning endpoints are compared to effects observed at community or populational level. Then, different PNECs are derived and presented : “traditional PNECs” covers conventional endpoints for at least three trophic levels (algae, crustaceans and fish), while “non conventional PNECs” may take account of the mesocosm study data obtained during the project but also of biomarkers response (e.g. biomarkers of effects such as immunotoxicological or respiratory burst effects). the ecological relevance of various enpoint is discussed.

Domaines: Toxicologie; Ecotoxicologie

Alice James, Anis Amara, Rémy Beaudouin, Anne Bado-Nilles, Gaëlle Daniele, et al.. Use of hazard assessment tools of increasing level of complexity for 2 pharmaceuticals : biological and ecological relevance. 1st International conference on risk assessment of pharmaceuticals in the environment (ICRAPHE), Sep 2016, Paris, France. ⟨ineris-01854270⟩