Examining pathways of PFAS exposure and their impacts on hyperlipidemia in a rural community impacted by land spreading

The National Institute of Environmental Health Sciences awarded the University of Wisconsin - Madison $3,343,688 on September 1, 2026, under the NIEHS Superfund Hazardous Substances Basic Research and Education program (CFDA 93.143) to examine pathways of per- and polyfluoroalkyl substances (PFAS) exposure and their impacts on hyperlipidemia in a rural community impacted by land spreading of biosolids and sludge.

The research addresses three gaps in PFAS science. The study will examine how lipid metabolism mediates PFAS health effects across a broader range of legacy and emerging PFAS compounds beyond the handful studied in prior human health research, despite over 10,000 PFAS existing. It will characterize precursor compounds such as polyfluoroalkyl phosphate esters (PAPEs) that industry has substituted for legacy PFAS and their bio-transformation into perfluorooctanoic acid (PFOA), a classified carcinogen. The project will also generate rural biomonitoring data, as existing data come predominantly from occupational and urban settings and overlook exposure pathways in agricultural areas where PFAS accumulates in soil, groundwater, surface water, and locally produced food. Wisconsin provides the study setting, where private wells contain some of the nation's highest PFAS levels (exceeding 36,000 parts per trillion), with contamination linked to biosolid and papermill sludge land spreading.

The performance period runs from September 1, 2026, through August 31, 2030, with work performed in Madison, Wisconsin.

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic "forever chemicals" that persist in the environment and human body, and are linked to kidney and liver cancers, thyroid disease, liver disease, and hyperlipidemia. An under-recognized source of PFAS exposure is from sludge and biosolids from wastewater treatment and industrial processes, which can be applied on agricultural fields as fertilizer. As a result, rural americans in agricultural settings are disproportionately at risk of contaminated food and water from land spreading. About 60% of biosolids generated in the united states are land- applied, yet the health implications for rural residents remain largely unknown. Three barriers limit progress. First, lipid metabolism is a key mechanism by which PFAS exposure may lead to downstream health outcomes. Yet prior human health studies have examined only a handful of legacy PFAS, despite >10,000 PFAS existing. Second, industry has replaced legacy PFAS with precursor compounds such as polyfluoroalkyl phosphate esters (PAPS), which can BIO-transform into perfluorooctanoic acid (PFOA), a classified carcinogenic. Some intermediates are orders of magnitude more toxic than their end products, yet little is known about their real-world contribution to human exposure. Third, biomonitoring data are largely from occupational or urban settings, overlooking rural pathways of exposure where PFAS accumulate in soil, groundwater, surface water, and locally produced food. Wisconsin provides a unique opportunity to address these gaps as IT has some of the nation's highest PFAS levels in private wells (>36,000 PPT), with contamination linked to biosolid and papermill sludge land spreading. We hypothesize that precursor PFAS significantly contribute to the persistence and burden of PFAS exposure, and that ongoing exposure via local food, water, air, and dust contributes to elevated lipid levels. Aim 1 will identify ongoing routes of exposure to PFAS in an impacted rural community by enrolling 400 residents, collecting environmental and blood samples, quantifying targeted and untargeted PFAS, and applying toxicokinetic modeling. Aim 2 will determine the relationship between PFAS mixtures and lipid profiles, testing whether inclusion of previously unidentified PFAS strengthens associations with cholesterol, triglycerides, and specific lipoprotein subfractions. The proposed research is of high impact and will significantly advance the field by clarifying our understanding of human exposure to PFAS from contaminated land spreading and key relationships between PFAS and hyperlipidemia. Findings will inform interventions aimed at reducing exposure among rural residents impacted by PFAS exposure from land spreading, and interventions aimed at preventing or treating elevated cholesterol from historic or current PFAS exposure - thereby reducing risks of downstream chronic health conditions.