Objective:

To investigate the effects of low-dose exposure to PFAS on cellular metabolism using a long-term cell culture model.

Key Findings:

• Limited intracellular accumulation of PFAS was observed, with PFOS stabilizing at around 0.40 ng/mg of cellular protein.
• PFOA remained below the detection limit throughout the study.
• Transcriptomic profiling indicated changes in oxidative stress pathways and lipid metabolism.
• Lipidomic measurements showed shifts consistent with membrane remodeling and altered lipid composition.

Interpretation:

Chronic PFAS exposure can trigger adaptive cellular responses despite low intracellular concentrations, suggesting toxicity may arise from interactions with cellular membranes rather than accumulation.

Limitations:

• The in vitro system may not fully represent the complex toxicokinetics and tissue-specific responses seen in vivo.

Conclusion:

The study highlights the potential for low-dose PFAS exposure to induce significant molecular changes in cellular metabolism, emphasizing the need for further research on PFAS toxicity mechanisms.