Department Environmental Toxicology

Effect-directed analysis

Effect-directed analysis links chemical analysis with biological effects testing. This allows focusing on environmental samples that actually affect biological systems. We have been using this approach to identify endocrine disruptors in various matrices (wastewater, treated effluent, surface waters, sediments, bile, adipose and muscle tissue).We are currently investigating the environmental impact of synthetic glucocorticoids (GCs), widely used anti-inflammatory and immunosuppressant pharmaceuticals. GCs mimic cortisol, the natural stress hormone, by acting through the glucocorticoid receptor (GR) and altering related gene expression patterns. GCs have been detected in the aquatic environment, and their predicted concentration range is 10-1000 ng/L (0.03-3 nM) in surface waters.

The immunosuppressive effects of GCs was examined in zebrafish embryos exposed to a model GC, then challenging them with bacterial lipopolysaccharides. The results indicate that GCs cause significant immunosuppression already at low nanomolar concentrations in fish. Based on an in-house developed broad-spectrum LC-MS/MS analysis method for endocrine disruptors targeting corticosteroid signaling (GCs), combined with an in vitro assay, we demonstrated the presence and activity of such compounds in various Czech and Swiss waters (effluent and river). Introducing the “cortisol equivalents fish plasma concentration” approach, we estimated an increase in fish glucocorticoid plasma level comparable to 0.9-83 ng/mL cortisol after exposure to river water. These results indicate that these chemicals may indeed impact wild fish.

As part of the EDA-EMERGE project, the same in vitro assay was used to identify GR-active sites in four European river catchments in Germany, Switzerland, the Czech Republic, Slovakia, Hungary and Croatia. Indeed, activity was found in all four catchments, mostly at sites impacted by wastewater treatment plants (WWTPs). A higher-tier EDA (HT-EDA) study (in collaboration with INERIS and the Department of Environmental Chemistry) is conducted at the GR-active Swiss site in order to identify the compounds responsible for the biological effect by fractionating the most active sample and examining the fractions with the bioassay. We are currently developing a GC-specific and sensitive biomarker-based assay using zebrafish embryos in order to replace the used in vitro assay which is human cell line based.

Publications

Schulze, T.; Ahel, M.; Ahlheim, J.; Aït-Aïssa, S.; Brion, F.; Di Paolo, C.; Froment, J.; Hidasi, A. O.; Hollender, J.; Hollert, H.; Hu, M.; Kloß, A.; Koprivica, S.; Krauss, M.; Muz, M.; Oswald, P.; Petre, M.; Schollée, J. E.; Seiler, T.-B.; Shao, Y.; Slobodnik, J.; Sonavane, M.; Suter, M. J. F.; Tollefsen, K. E.; Tousova, Z.; Walz, K.-H.; Brack, W. (2017) Assessment of a novel device for onsite integrative large-volume solid phase extraction of water samples to enable a comprehensive chemical and effect-based analysis, Science of the Total Environment, 581, 350-358, doi:10.1016/j.scitotenv.2016.12.140, Institutional Repository
Ammann, A. A.; Macikova, P.; Groh, K. J.; Schirmer, K.; Suter, M. J. F. (2014) LC-MS/MS determination of potential endocrine disruptors of cortico signalling in rivers and wastewaters, Analytical and Bioanalytical Chemistry, 406(29), 7653-7665, doi:10.1007/s00216-014-8206-9, Institutional Repository
Macikova, P.; Groh, K. J.; Ammann, A. A.; Schirmer, K.; Suter, M. J. -F. (2014) Endocrine disrupting compounds affecting corticosteroid signaling pathways in Czech and Swiss waters: potential impact on fish, Environmental Science and Technology, 48(21), 12902-12911, doi:10.1021/es502711c, Institutional Repository