Objectives
The main objective of WP6-Risk Assessment is to characterise and quantify impacts of persistent and mobile substances on human health and the environment.
This will be achieved by developing the following:
▼ Better models for external human exposure to persistent and mobile substances
▼ Models translating in vitro effect concentrations ↔ human relevant internal doses ↔ external exposure scenarios
▼ Toolbox for persistent and mobile hazard assessment (main toxicological endpoints)
▼ Risk matrix for screening and prioritization of persistent and mobile substances
▼ Identification of bioactive persistent and mobile contaminants of emerging concern
There is currently limited understanding related to the risks associated with long term chronic exposure to persistent and mobile substances in drinking water or the environment, and how to foresee these hazards or risks. Existing tools used for chemical exposure assessment in regulatory guidelines are likely inappropriate to predict exposure concentrations of persistent and mobile substances in drinking water, as they do not account for key exposure pathways, like groundwater extraction or bank filtration. Methods are needed to improve and expand the applicability domain of existing environmental fate and exposure models, that take into consideration the intrinsic persistent and mobile substance properties, including ionic interactions. For mobile substances, robust hazard assessment frameworks are also urgently needed, incorporating innovative human-relevant methods to facilitate a refined understanding of the persistent and mobile substance’s mechanisms of toxicity. This paradigm shift is partly fueled by the need to reduce, refine and replace animal testing for ethical reasons (i.e. the 3R principle), but also for scientific reasons. New approach methodologies (NAMs) rely on integrated approaches for effects testing and assessment which combine data from a battery of human in vitro and in silico models to inform the hazard assessment. For the risk assessment of persistent and mobile substance groups, an understanding of the mode of action regarding shared toxicodynamic and toxicokinetic properties is thus needed. Human in vitro methods can elucidate mechanisms of adverse health effects, such as via the quantification of changes in cellular signaling pathways in human-relevant cells or tissues. In ZeroPM, NAMs will be integrated and used to leverage the read-across framework to investigate the hazards of substances grouped and prioritized.
The Team
WP6 is lead by Dr. Timo Hamers (VU) along with Dr. Marjorie van Duursen (VU), and will be a collaboration with many experts. These include Dr. Todd Gouin (TGER) who will lead external exposure assessment work (with WP5), Dr. Sylvia Escher (ITEM) who will lead the PBPK modelling and assist with databases and data mining (also with WP5), colleagues at VU who will lead the development of in silico, in vitro and in vivo toolboxes for persistent and mobile substance hazard assessment, Dr. Stefan Hahn and Dr. Annette Bitsch who will lead the development of a risk matrix for screening and prioritization, and finally the inclusion of EDA analysis from technical solutions (WP7) will be assisted by Dr. Marcel Riegel and Lukas Lesmeister to identify transformation products.
VU | Vrije Universiteit Amsterdam (VU) De Boelelaan 1105 1081 HV Amsterdam, Netherlands |
 | Dr. Timo Hamers WP6 leader |
 | Dr. Marjorie van Duursen |
| PhD student/postdoc | |
 | Fraunhofer Institute for Toxicology and Experimental Medicine ( ITEM) Nikolai-Fuchs-Straße 1 30625 Hannover, Germany |
 | Dr. Sylvia Escher |
 | Dr. Annette Bitsch |
 | Dr. Stefan Hahn |
| Norman Nowack (PhD student) | |
 | TG Environmental Research (TGER) 18 Wellpond Close Sharnbrook, Bedford, England MK44 1PL, United Kingdom |
 | Dr. Todd Gouin |
 | DVGW-Technologiezentrum Wasser (TZW) Karlsruher Straße 84 76139 Karlsruhe |
 | Dr. Marcel Riegel |
 | Lukas Lesmeister PhD student |