Blood lipid profiling to explore effects of PFAS with relevance for cardiovascular disease in humans

The estimated exposure and reported serum levels of PFAS, show that parts of the general population exceed the tolerable weekly intake and the highest exposure occur in areas with contaminated drinking water.

One of the main human health concerns associated with PFAS exposure is perturbation of blood lipid homeostasis observed in epidemiological studies.

Current risk assessments are hampered by a lack of understanding on the mode of action and the potential causal relationship with cardiovascular disease. In addition, combined effects of PFAS mixtures remain largely unknown.

In this project we will elucidate the lipidomic profiles (lipidomics) in human blood samples representing populations with high and low levels of exposure.

We will also use a prospective nested case-control study to identify lipid profiles associated with an increased risk of cardiovascular disease.

Identified biomarkers from the epidemiological studies will be compared with results from experimental in vitro studies using human hepatocytes (HepaRG).

This cell model will also be used to study the cellular regulation of lipids in relation to various PFAS and human relevant mixtures.

By integration of the benchmark dose-response modelling approach, results from epidemiological and experimental studies will be transferable to a regulatory context and relevant for retrospective risk assessments as well as for prospective safety evaluations.