IMAG/MSM WG Multiscale Modeling and Viral Pandemics Zoom

To join the meeting:
https://iu.zoom.us/meeting/register/tZYqd-2srD8tGtCXDem4Cka08rBz5fDW0EQR

Please feel free to forward this invitation to anyone you think would be interested.

Thursday January 9, 2025 at 3:00PM (EST)

Martina Iulini, Università degli Studi di Milano, will discuss: Using NAMs to address PFAS immunotoxicity: an integrated in vitro and in silico testing strategist to study the effect on the antibody production

Perfluorinated substances (PFAS) are a class of synthetic chemicals widely used in industry to which people and the environment are exposed. Human studies have shown that PFAS can cause immunosuppression, lower resistance to disease, and an increased risk of infections with a decreased response to vaccination. However, not much is known about the mechanism of action via which these substances act. The aim of the project was to evaluate the immunotoxic effects of PFAS and identify underlying mechanisms through the design of new approach methodologies (NAMs) based approaches. To reach these goals, an integrated testing strategy (ITS) consisting of in vitro and in silico methods was developed. Based on the in vivo evidence of reduced antibody production, suitable in vitro models were identified to evaluate the most relevant in vivo effect for PFAS immunotoxicity. The effects of PFAS on the most important immune cells were studied using only human models, and the results obtained with the selected NAMs supported the in vivo evidence. Furthermore, mathematical fate and distribution models were used to identify nominal concentration of PFAS in the in vitro cell system and physiologically based kinetics model was used to perform quantitative in vitro to in vivo extrapolation. Moreover, the ‘Universal Immune System Simulator’ was used to complete the ITS and investigate the effects also on vulnerable populations and predict threshold doses for which we have an immune adverse outcome effect. In accordance with data present in the literature, the in silico results obtained from this study evidence an immunosuppressive effect in the models used, with differences between the four selected PFAS. To conclude, the results support the in vivo evidence of possible reduced resistance to infections with lower antibody response. Besides, the chosen ITS were able to allow the study of PFAS in models that took into account both the dynamics and kinetics of the compounds using only the use of alternative methods. 
Link to publications: Corsini et al, EFSA Journal, https://efsa.onlinelibrary.wiley.com/doi/abs/10.2903/sp.efsa.2024.EN-8926 
Funding: This study was supported by the European Food Safety Authority (Case Studies NAMS_PFAS Immunotox - OC/EFSA/SCER/2021/13) and from Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN2022, Project number 2022KS9FZX).