BACKGROUND

Global contamination of soil and aquatic ecosystems by pharmaceutical and microbiological pollutants (such as antimicrobial-resistant microorganisms and/or pathogens) raises severe concerns about impacts on ecosystem health and repercussions on humans and animals. Preserving ecosystems from adverse ecotoxicological effects of pharmaceuticals and their transformation products, and limiting the environmental spread of antimicrobial resistance and pathogens is imperative to reach several UN Sustainable Development Goals as well as the European Green Deal, Water Framework Directive and Biodiversity Strategy for 2030. In this context, the main scientific objective of Pharm-ERA is to develop and implement innovative concepts, methods and strategies to improve the monitoring and assessment of the environmental effects and risks of pharmaceuticals, their transformation products, antimicrobial resistances and pathogens from terrestrial to aquatic environments. The ultimate goal is to provide scientific evidence and expertise to contribute to reducing the environmental spread and impact of these chemical and microbiological contaminants and to preserve microbial diversity and functions across the soil-water-sediment continuum.

DESCRIPTION OF THE PhD PROJECT

Pharmaceuticals are widespread in aquatic ecosystems and are known to potentially affect aquatic organisms (Hejna et al., 2022; Cannata et al., 2024), depending on their behaviour in the environment. The hazard assessment of a pharmaceutical in the environment is commonly performed in the laboratory, under controlled conditions and based on biological organism testing amongst others. However, these studies are usually very time-consuming and costly and there is a need for a more efficient and rapid process to evaluate the toxicity and fate of potentially dangerous chemicals. Furthermore, we are now in the era of the 3Rs (reduction, replacement, refinement of vertebrate animal testing) where regulators are increasingly calling for new alternative methodologies (NAMs) to reduce the number of organisms involved in ecotoxicological testing (OECD, 2020). A promising solution is the use of in silico methodologies which consist of using existing data like effect concentrations or water solubility values, among others, to predict biological and chemical properties (e.g. toxicity, bioaccumulation, biodegradability).
The aim of this PhD project is to understand the behaviour of a set of pharmaceutical compounds in aquatic ecosystems and their toxicity to aquatic organisms, to ultimately reliably predict their ecotoxicity based on their mechanism of toxic action. Thus, this project lies at the interface of analytical and environmental chemistry, ecotoxicology and regulation and involves both laboratory experiments and model developments. Once the set of pharmaceuticals and potentially related transformation products (TPs) is defined, the first objective of the project is to characterise the fate and behaviour (especially in terms of TPs occurrence) of the selected pharmaceuticals in sediment and surface waters following OECD test guidelines. The detection and identification of potential TPs will be carried out by liquid chromatography coupled with high-resolution mass spectrometry LC-HRMS using an approach implemented at INRAE (Rocco et al. 2022). A second objective is to assess acute and chronic effects of the selected pharmaceuticals including also potentially the TPs to sediment and surface water organisms using single-species bioassays (e.g. Lumbriculus, chironomids, algae, ostracods, gammarids, daphnids, fish). In silico approaches developed at KREATiS are strongly anchored into the mechanistic understanding of chemical effects on biological organisms (Bauer et al., 2018). Therefore, the third objective is to understand the mechanism of toxic action of the selected chemicals on organisms in different trophic levels using existing data to support the development of predictive ecotoxicological models for pharmaceuticals and develop structural alerts. Finally, the fourth objective of the project is to develop models (e.g. (Quantitative) Structure-Activity Relationship, sophisticated machine learning approach) to predict quantitatively the toxicity of certain pharmaceutical structures, including also the relevant TPs, on water and sediment organisms.