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

Authors: BAUMERT, BRITTNEY - University Of Southern California; FISCHER, FABIAN - Harvard University; NIELSEN, FLEMMING - University Of Southern Denmark; GRANDJEAN, PHILIPPE - University Of Rhode Island; BARTELL, SCOTT - University Of California Irvine; STRATAKIS, NIKOS - Barcelona Institute For Global Health, Isglobal; WALKER, DOUGLAS - Emory University; VALVI, DAMASKINI - The Icahn School Of Medicine At Mount Sinai; KOHLI, ROHIT - Children'S Hospital Los Angeles; INGE, THOMAS - Northwestern University; RYDER, JUSTIN - Northwestern University; JENKINS, TODD - University Of Cincinnati College Of Medicine; SISLEY, STEPHANIE - Children'S Nutrition Research Center (CNRC); XANTHAKOS, STAVRA - University Of Cincinnati College Of Medicine; ROCK, SARAH - University Of Southern California; LA MERIILL, MICHELE - University Of California, Davis; CONTI, DAVID - University Of Southern California; MCCONNELL, ROB - University Of Southern California; CHATZI, LIDA - University Of Southern California

Submitted to: Environmental Science and Technology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2023
Publication Date: 9/27/2023
Citation: Baumert, B.O., Fischer, F.C., Nielsen, F., Grandjean, P., Bartell, S., Stratakis, N., Walker, D., Valvi, D., Kohli, R., Inge, T., Ryder, J., Jenkins, T., Sisley, S., Xanthakos, S., Rock, S., La Merrill, M.A., Conti, D., McConnell, R., Chatzi, L. 2023. 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. Environmental Science and Technology. 57:14817-14826. https://doi.org/10.1021/acs.est.3c02765.
DOI: https://doi.org/10.1021/acs.est.3c02765

Interpretive Summary: Chemicals referred to as PFAS (polyfluoroalkyl substances) have been linked to liver dysfunction in animal studies, but if that happens in humans was unknown. Researchers in Houston, Texas analyzed how PFAS build up in people's bodies, especially in the liver. They looked at blood and liver samples from 64 teenagers who had weight loss surgery. They found that one type of PFAS, called PFHpA, collected in the liver much more than other tissue types. Using computer models, they were able to create a way of predicting how much PFAS would be in a person’s liver from their blood levels. This study can be used in the future to understand how PFAS move around in our bodies and which organs might be most affected.

Technical Abstract: 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.