Expanding the Scope of PFAS Research to Include Adipose Tissues

The occurrence and burden of per- and polyfluoroalkyl substances (PFAS) in adipose tissue of humans and wildlife represent an underexamined dimension of PFAS exposure. While most PFAS research has focused on ionic substances that accumulate in tissues such as liver and blood, there is growing evidence that a distinct and diverse suite of neutral PFAS bioaccumulate in adipose tissue. This Perspective synthesizes recent data illustrating the substantial contribution of some adipose-associated PFAS to overall body burdens, applies quantum chemical modeling to exemplify additional PFAS likely to partition into adipose tissue, and examines analytical blindspots that have limited their detection to date. We show that certain neutral PFAS possess partitioning properties comparable to legacy persistent organic pollutants, which, provided that they are sufficiently persistent, can lead to bioaccumulation in adipose tissue. We further outline the analytical challenge of extracting, detecting, and quantifying neutral PFAS in matrices rich in storage lipids and discuss the implications for exposure assessment, toxicology, and environmental surveillance. Finally, we identify key research needs and call for expanded monitoring strategies that capture the full chemical space of PFAS bioaccumulation.