1 research outputs found
Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation
Animal studies have pointed at the liver as a hotspot
for per-
and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however,
these findings have not been replicated in human populations. We measured
concentrations of seven PFAS in matched liver and plasma samples collected
at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal
Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration
ratios were perfectly explained (r2 >
0.99) in a multilinear regression (MLR) model based on toxicokinetic
(TK) descriptors consisting of binding to tissue constituents and
membrane permeabilities. Of the seven matched plasma and liver PFAS
concentrations compared in this study, the liver:plasma concentration
ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than
the liver:plasma concentration ratio of other PFAS congeners. Comparing
the MLR model with an equilibrium mass balance model (MBM) suggested
that complex kinetic transport processes are driving the unexpectedly
high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling
pointed to membrane lipids as the tissue constituents that drive the
liver accumulation of long-chain, hydrophobic PFAS, whereas albumin
binding of hydrophobic PFAS dominated PFAS distribution in plasma.
The liver:plasma concentration data set, empirical MLR model, and
mechanistic MBM modeling allow the prediction of liver from plasma
concentrations measured in human cohort studies. Our study demonstrates
that combining biomonitoring data with mechanistic modeling can identify
underlying mechanisms of internal distribution and specific target
organ toxicity of PFAS in humans