In protein binding, PFAS attaches to blood plasma or proteins, an interaction which affects the distribution and impact of PFAS. In this study, STEEP researchers examined binding comparatively across rats, mice, and humans, focusing on albumin, a protein produced in the liver, and plasma, the liquid component of blood that makes up about 55% of blood volume. Although biological effects and specific protein binding of PFAS have been examined, research is lacking when focused on species-specific fraction unbound (fu) PFAS in plasma, as well as related toxicokinetics: how the body absorbs, distributes, metabolizes, and excretes PFAS.
A presaturation equilibrium dialysis method, a technique used to determine the free fraction of highly protein-bound compounds, was used to measure and validate the binding of 14 individual PFAS with carbon chains containing 4 to 12 perfluorinated carbon atoms and several functional head-group molecules. Testing between each species-matrix combination showed positive correlation between
rat and human when comparing binding to albumin and fu in plasma. Similar trends in binding were also observed for mouse albumin and plasma. PFAS characteristics, such as molecular weight, chain length, and ability to dissolve in lipids and fats were found to have important roles in plasma protein binding of PFAS.
The methodology used in this study is novel in the PFAS field, and the study compared species differences, providing valuable insights for further bioaccumulation, elimination half-life, and toxicity research. PFAS as contaminants continue to persist and accumulate in the environment. This research helps to understand trends to better inform environmental impact and toxicity, in hope that strategies can be developed to better minimize exposure and accumulation of these chemicals.
Ryu S, Burchett W, Zhang S, Modaresi SMS, Agudelo Areiza J, Kaye E, Fischer FC, Slitt AL. Species-Specific Unbound Fraction Differences in Highly Bound PFAS: A Comparative Study across Human, Rat, and Mouse Plasma and Albumin. Toxics. 2024; 12(4):253. https://doi.org/10.3390/toxics12040253
