Targeted and non-target cell-based metabolomics and lipidomics to identify molecular mechanisms and pathways involved in toxicity of PFASs

Develop cell- and organ-on-chip-based metabolomic and lipidomic approaches using human adrenal cortex to: 1) clarify the molecular mechanisms involved in the toxicity of alternative PFASs with a focus on steroidogenesis, cholesterol synthesis and metabolism, and lipid pathways, 2) link the metabolomic pathways with human cohort gene expression and metabolomics data of ESR9, and 3) perform competitive binding studies with L-FABP using mixtures of different substrates (fatty acids, cholesterol) and different PFAS compounds, 4) support AOP- and biomarker-development with a focus on intermediary metabolic events of relevance for suspected human health outcomes following PFAS exposure.