Risk Assessment

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.

Photo by Filip Urban on Unsplash
VUVrije 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