posted on 2024-01-03, 13:33authored byFabian Christoph Fischer, Sophia Ludtke, Colin Thackray, Heidi M. Pickard, Faiz Haque, Clifton Dassuncao, Satoshi Endo, Laurel Schaider, Elsie M. Sunderland
Per-
and polyfluoroalkyl substances (PFAS) are a diverse class
of highly persistent anthropogenic chemicals that are detectable in
the serum of most humans. PFAS exposure has been associated with many
adverse effects on human health including immunotoxicity, increased
risk of certain cancers, and metabolic disruption. PFAS binding to
the most abundant blood serum proteins (human serum albumin [HSA]
and globulins) is thought to affect transport to active sites, toxicity,
and elimination half-lives. However, few studies have investigated
the competitive binding of PFAS to these proteins in human serum.
Here, we use C18 solid-phase microextraction fibers to measure HSA–water
and globulin–water distribution coefficients (DHSA/w, Dglob/w) for PFAS with
carbon chains containing 4 to 13 perfluorinated carbons (ηpfc = 4–13) and several functional head-groups. PFAS
with ηpfc < 7 were highly bound to HSA relative
to globulins, whereas PFAS with ηpfc ≥ 7 showed
a greater propensity for binding to globulins. Experimentally measured DHSA/w and Dglob/w and concentrations of serum proteins successfully predicted the
variability in PFAS binding in human serum. We estimated that the
unbound fraction of serum PFAS varied by up to a factor of 2.5 among
individuals participating in the 2017–2018 U.S. National Health
and Nutrition Examination Survey. These results suggest that serum
HSA and globulins are important covariates for epidemiological studies
aimed at understanding the effects of PFAS exposure.