Exploring the PFAS alternatives-induced immunotoxicity and impact on intercellular communication.

Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants which are highly persistent in the environment with multiple hazardous properties including immunomodulation/immunotoxic potency. Human exposure to PFASs has been associated with various immune-mediated diseases and outcomes.

Recently the European Chemicals Agency (ECHA) called for a gradual ban of over 10,000 PFAS compounds in Europe.

As concerns grow about the persistence and toxicity of PFAS, the market has shifted towards new PFAS alternatives, however, little is known about the potential risks of these newer chemicals.

PFASs have now widely been replaced in many consumer products with PFASs with longer carbon-chains, like perfluoroundecanoic acid (PFUnDA).

Rising exposure levels of PFUnDA has been already observed and it was reported previously to have negative effect on the immune system in vitro and in vivo.Blood plasma transports mRNA that modulate immune responses and also extracellular vesicles (EVs) that play key role in intercellular communicationthat and can transport biologically relevant cargo, including microRNAs (miRNAs), and may partly mediate the effects of pollutants on the immune system.

This project aims to determine how new PFAS alternatives affect the immune system in long term exposure.

To fully understand the mechanisms and to address the multifaceted nature of chemical induced immunotoxicity, the study focuses on changes of key mRNA biomarkers related to the immune system and on the EV-miRNA cargo of extracellular vesicles in long term PFUnDA exposure.

Our goal is to develop a multi-biomarker palette identifying key mRNAs and EV-miRNAs in zebrafish to screen novel chemicals for their immunotoxic potency, that is high throughput, quick and easily measured from blood.