Prioritize

A recent survey concluded there were 350 000 chemicals and mixtures of chemicals on the global chemical market. The number of these chemicals that are persistent and mobile substances as well as their emissions, is unknown. To date, the most comprehensive assessment of persistent and mobile substances on the global market has been carried out for the entire REACH registered substance list of May 2017. The list consisted of a mere 15 469 chemical substances that were manufactured or imported into the EU at 1 tonn/year or more. The study concluded that 122 substances were of highest priority when considering toxicological hazards and potential likelihood for widespread exposure, based on production volumes, usage, or monitoring studies. Screening and prioritizing chemicals used by industry by ranking them according to their exposure and hazard potential is an efficient, transparent and robust path towards achieving zero pollution, as it identifies those persistent and mobile substances to focus efforts on first.

The need to manage entire groups of persistent and mobile substances, rather than individual ones as part of policy or market strategies has been highlighted. An example is the Chemicals Strategy which calls to group all PFAS as similarly hazardous, in addition to many of them being potentially mobile or toxic. ZeroPM will thus strive to group all persistent and mobile substances on the global chemical market and their transformation products in a meaningful way, based on molecular substructure and other considerations. The performance of the grouping approach developed for prioritizing substances will be evaluated via the second hypothesis of ZeroPM:

ZeroPM’s hypothesis – Grouping persistent and mobile substances based on specific molecular substructures will support persistent and mobile substance prioritization and directed risk assessment procedures

To ground-truth this hypothesis, it is necessary to characterize the potential risks of the persistent and mobile substance groups to the environment or human health; and if demonstrated, subsequently, prioritize which persistent and mobile substances and substance groups require the most attention. The risk of a persistent and mobile substance is quantified through its exposure and hazards.

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. This work will be the basis of hypothesis three:

ZeroPM’s hypothesis – Identifying which PM substance groups pose the most risk through NAMs for exposure assessment and toxicity testing will indicate at least one or more persistent and mobile substance group where exposure needs to be reduced to protect the environment and human health (excluding PFAS)

ZeroPM will advance ways to priortize persistent and mobile substance groups through two work packages:

WP5 Substance Grouping will prioritize persistent and mobile substances and substance groups on the global chemical market for prevention and removal.

WP6 Risk Assessment will to characterise and quantify impacts of persistent and mobile substances on human health and the environment.

The two “prioritize” work packages