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Strategies for health protection, pollution Control and Elimination of Next generAtion RefractIve Organic chemicals from Soil, vadose zone and water. (SCENARIOS)

11/2021-10/2025

Funding programme / funding institution: Europäische Union

Grant number: 101037509

Project homepage: -

Project description:

Poly- and perfluorinated compounds (PFAS) are industrial chemicals that are used for a large number of products with water and dirt-repellent properties. The group of PFAS currently consists of more than 5000 different compounds, for most of which little or no data are available regarding their distribution, use and toxicological properties. PFAS are extremely stable compounds and, due to their persistence, are considered to be global environmental contaminants in soil, water and the air. As part of its Green Deal program, the EU is funding the SCENARIOS project, in which 19 project partners are working on innovative solutions to the global problems associated with the manufacture and use of PFAS. The aims of the joint project are (i) the development of fast and inexpensive methods for the detection and quantification of PFAS in environmental and biological samples, (ii) the development of integrated approaches to testing and assessment (IATA) of PFAS, especially with regard to their human toxicity and ecotoxicity, and (iii) the development and implementation of innovative technical solutions for the remediation of PFAS-contaminated soils and waters.

In the SCENARIOS project, the BfR leads the work package that deals with the assessment of the risks of PFAS for both the environment and human health. The following tasks are to be tackled together with various project partners in the SCENARIOS consortium:

1. Since not all of the currently more than 5000 different PFAS compounds can be comprehensively characterized, strategies for PFAS prioritization should be developed. Prioritization should include published data on PFAS levels in soil, water and the air (environmental sector), in food and drinking water (external exposure of humans) and in human blood samples (internal exposure). Literature data will also be screened with regard to PFAS toxicity, and computer models (QSAR, read across) will be employed for toxicity prediction. The aim is to identify those PFAS which, due to their distribution and their toxicological properties, have to be examined and evaluated with high priority, thereby having a focus on those compounds for which little or no data are available (poor-data PFAS).
2. On the basis of this prioritization, high-priority PFAS should be examined in detail experimentally. This should be done using well-established, simple and fast in vitro test systems that also allow high throughput screening. The aim is to investigate numerous endpoints which are associated with a variety of diseases of liver, lung, thyroid, endocrine system and immune system, thereby including intestine and skin as additional organs. The aim is to generate in vitro data on dose-effect relationships for various endpoints, which are to be used for modeling (point 5) and finally for deriving toxicological reference points (e.g. in vitro point of departure). In addition to individual compounds, various relevant PFAS mixtures should also be examined in order to map the real exposure of the consumer to mixtures of PFAS.
3. In the SCENARIOS consortium, various three-dimensional (3D) cell culture systems are established as models for the organs lung, intestine and skin. By using various omics methods, these systems will be used to comprehensively investigate the alterations that are induced by PFAS in these cells. The focus is on studies of alterations at the level of gene expression (transcriptomics), DNA methylation (methylomics), protein expression (proteomics) and lipid synthesis (lipidomics). The results of these omics approaches will be integrated by subsequent network analyzes and will eventually lead to the identification of new, previously unknown effects of PFAS at the molecular level. For these new molecular targets, additional in vitro tests will – as far as possible – be established, which will be integrated into the in vitro test battery mentioned under point 2.
4. Zebrafish (Danio rerio) is an established model organism for toxicity studies. This model system will be used to investigate to what extent PFAS lead to organ damage in adult fish and to developmental disorders in fish embryos. In addition, results obtained in vitro (point 2) or as part of the omics studies (point 3) are validated in vivo, for example by examining alterations in gene expression in various zebrafish organs. In turn, data for PBPK modeling (point 5) and for the derivation of toxicological reference points (e.g. in vivo point of departure) should be generated via dose-effect relationships.
5. Physiologically-based pharmacokinetic (PBPK) modeling is a mathematical method that can be used to calculate – based on dose-response relationships – internal exposure from external exposure scenarios. With regard to toxicological reference values ??(e.g. point of departure; POD), in vitro data can be transferred to the in vivo situation (in vitro to in vivo extrapolation; IVIVE). First, PBPK models will be developed and validated for PFAS that are well characterized and for which a broad database is available (e.g. PFOS, PFOA). In a second step, these models are used for PFAS for which only few data are available to calculate either the internal exposure from data on external exposure (e.g. from PFAS concentrations in food) (forward dosimetry) or the external exposure from existing PFAS biomonitoring data (reverse dosimetry).
6. The concept of "Adverse Outcome Pathways" (AOP) is a relatively new risk assessment concept, in which effects of substances at the molecular level (e.g. from in vitro studies or results from omics studies) are used to correlated them with toxicologically relevant effects on tissues, organs and finally on the entire organism. The data generated in points 2 to 5 are compared with existing AOPs in order to clarify whether the molecular effects of PFAS could possibly be associated with one or more disease pattern (adverse outcomes). In addition, the data can also be used to generate new AOPs or to refine existing AOPs or those under construction.
7. As a final goal, the results generated in points 2 to 6 should be used for the development of integrated approaches to testing and assessment (IATA) of PFAS. To date, risk assessments have only been carried out for a few well-characterized PFAS - most of the approximately 5000 PFAS compounds could not be assessed so far due to the limited data on exposure and toxicity. The IATA approach for PFAS is intended to show strategies with which individual PFAS or groups of PFAS with similar properties can be assessed despite limited data, both with regard to ecotoxicity and human toxicity. Ultimately, the IATA concept to be developed in SCENARIOS should enable risk assessment authorities to tackle the assessment of the large and complex group of PFAS.
8. For some well-characterized PFAS (PFOS, PFOA, PFNA, PFHxS) it was shown that these compounds impact the immune system in such a way that the immune response in children is lower after certain vaccinations. A negative association was observed between the blood serum concentrations of these PFAS and the antibody titers in the children after the vaccinations. The SCENARIOS consortium has access to a cohort of approx. 300 people in northern Italy who have consumed PFOA-contaminated drinking water over a longer period of time due to an unintentional industrial-related entry of PFOA into the environment and who now have significantly higher PFOA blood serum levels than the normal population. In the course of the vaccination campaign against Covid-19, this cohort is to be used to check whether the observed negative association between PFOA blood levels and antibody titers after vaccinations also applies to vaccinations against Covid-19. In addition to the antibody titers against Covid-19, a large number of other immune parameters are to be examined and the impact of PFOA on these parameters is to be characterized.

Project partners

• Università Piemonte Orientale
• Università del Salento
• Ben-Gurion University of the Negev
• ?δρυμα Τεχνολογ?ας και ?ρευνας (ΙΤΕ)
• Universidad de Castilla-La Mancha
• Sensoil Innovations Ltd
• LOMARTOV SL
• Luxembourg Institute of Science and Technology
• National Technical University of Athens
• Novamechanics LTD
• Tampere University of Applied Sciences
• University of Birmingham
• Envytech Solution AB
• Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo di Alessandria
• GEO
• IDP Ingenieria Y Arquitectura Iberia SL
• COMET Global Innovation and Commercialization
• Polo d'innovazione di Genomica, Genetica e Biologia

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