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Innovative tools to study the impact and mode of action of micro and nanoplastics on human health: towards a knowledge base for risk assessment

Periodic Reporting for period 1 - PLASTICHEAL (Innovative tools to study the impact and mode of action of micro and nanoplastics on human health: towards a knowledge base for risk assessment)

Reporting period: 2021-04-01 to 2022-09-30

Humans are exposed to micro and nanoplastics (MNPLs) due to their ubiquitous presence in the environment, but there is only very limited information on the potential impact of this exposure on human health. Therefore, the current regulatory framework cannot ensure that MNPLs present in the air, and in food and beverage products are at safe levels for the population.
In this context, the PLASTICHEAL project aims at providing new methodologies and evidence to regulators by combining the use of breakthrough research and reliable test methods to set the knowledge basis for adequate risk assessment of MNPLs.
The project will first generate human exposure estimates after identification, measurement, and characterization of MNPLs present in the environmental air, water, and food sources, as well as in human biological samples of population groups with potentially high MNPLs exposure levels. Then a variety of complementary experimental models and methodologies will be applied to screen for several potential MNPLs-induced effects. The data generated will be processed by integrative analysis methods to obtain MNPLs mechanistic insight, and to identify key events with the potential to be consolidated as novel biomarkers of MNPLs long-term effects. The knowledge gained and the methodology developed in PLASTICHEAL will permit the identification and management of safety issues related to human exposure to MNPLs.
PLASTICHEAL, which has received 6 million euros from the European Union’s Horizon 2020 Research and Innovation Programme, is coordinated by the Autonomous University of Barcelona and has the participation of 10 universities and research centres from Finland, The Netherlands, Denmark, France, Spain, United Kingdom and Germany.
The work carried out during this first reporting period has covered the different proposed tasks, as well as the planned objectives. Thus, regarding the genesis of reference MNPL materials, PET, PE, and PLA were synthesized using an up-down approach. Furthermore, true-to-life materials (PET from water-plastic bottles; titanium-dopped PET from milk bottles; and PLA from tea bags) were also obtained/characterized and used. In parallel, the tools to identify such MNPLs in environmental/biological matrices are going on.
Fate and in vivo (mice and Drosophila) distribution of selected MNPLs is going on and their uptake and in vitro distribution have also been done in a wide set of cell lines. Results indicate an important internalization in all the models. The potentially harmful effects of the obtained MNPLs have been determined using a wide set of biomarkers, including those detecting immunological changes, genotoxicity, and carcinogenicity; these last biomarkers use long-term exposure approaches. Slight, but significant effects have been observed for some of these biomarkers. Furthermore, complex barrier models of the GIT and RT, and lung organoids have been established showing the uptake of the used MNPLs .
Biomonitoring studies are ready to start. The ethical aspects have been overcome, the agreement of the participants/employers has also been reached, and the aspects related to the environmental/biological samples discussed inside the consortium. Next February/March sampling will start.
It is important to point out that the obtained results have been already published in 13 papers and 1 book chapter. Furthermore, 9 more papers have been already sent for their future publication. PLASTICHEAL members have spread their work in multiple conferences and meetings as well as in other different media.
Although with a bit of delay, due to the complexity of the task, the new reference-MNPLs generated by PLASTICHEAL will be relevant for further hazard assessment. Especially relevant are the true-to-live MNPLs that have changed the initial paradigm moving from the pristine synthetic MNPLs which are not representative of the environmental secondary MNPLs. Other relevant results will be the in vivo studies which will permit us to determine their fate in exposed humans. Barrier model studies have moved on from the classical models, by incorporating new models as primary nasal and endothelial barriers, in addition to the lung organoid models, which better mimicry structure and functionality. The carcinogenic risk of MNPLs is an unexplored field. PLASTICHEAL research using NAMs approaches evaluating a wide set of cancer hallmarks will apport useful data to decipher the relevance of this potential risk.
Finally, we are confident that human biomonitoring data will apport definitive data for the risk assessment of MNPLs, as the ultimate aim of PLASTICHEAL
Confocal Raman Microscopy images of polystyrene beads in mouse lungs
Project overview
Red stained nanoPET in Drosophila larvae
Polystyrene beads (green) internalization by Raji-B cells
Polystyrene beads (green) internalization by J774A murine macrophages
Polystyrene beads (green) internalization by Caco-2 cells