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
Year: 2023
Type: article
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 ( r 2 > 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.
Authors: Brittney O. Baumert, Fabian C. Fischer, Flemming Nielsen, Philippe Grandjean, Scott Bartell, Nikos Stratakis, Douglas I. Walker, Damaskini Valvi, Rohit Kohli, Thomas Inge, Justin Ryder, Todd Jenkins, Stephanie Sisley, Stavra Xanthakos, Sarah Rock, Michele A. La Merrill, David Conti, Rob McConnell, Lida Chatzi
Institutions: University of Southern California, Harvard University, University of Southern Denmark, University of Rhode Island, University of California, Irvine, Barcelona Institute for Global Health, Emory University, Icahn School of Medicine at Mount Sinai, Children's Hospital of Los Angeles, Northwestern University, Lurie Children's Hospital, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Baylor College of Medicine, Children's Nutrition Research Center at Baylor College of Medicine, University of California, Davis
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Funders: U.S. Department of Agriculture, California Environmental Protection Agency, European Commission, Ministerio de Ciencia e Innovación, National Institutes of Health, Agencia Estatal de Investigación, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences
Awards: G1023656628, G1175115578, G1199430394, G1292929380, G1339695942, G1480891745, G1583036818, G1855990336, G1869699344, G1897593783, G210041235, Continuation of Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS), Biostatistics Research Center, G2114305129, G2127563502, G2262748287, G2309174360, G2440497473, G244766491, Environmental Genomics, G2601397997, G2647375232, Developmental Exposure to Perfluoroalkyl Substances and Cardiometabolic Outcomes in Adulthood: Potential Links via the Plasma Metabolome, G279363373, G2953531637, G300979063, G31452788, G3173997727, G3180099256, Environmental Chemical Exposures and Longitudinal Changes of Glucose Metabolism, Insulin Sensitivity and B Cell Function in Youth, G3249297036, G34346518, G346198372, G3480869486, G3518538256, G3530506875, G3681454997, G4042783231, G4097835671, G425668148, G430777504, Developmental origins of child liver injury: Effects of prenatal environmental exposures, G444661368, Effects of DDE exposure on adipose tissue function, weight loss and metabolic improvement after bariatric surgery: A new paradigm for study of lipophilic chemicals, G5080475149, G5159276886, G521056402, G5229491074, G5421974903, G57626283, G589846866, G6165125548, G6791272909, G6968487272, G702470302, G7208110030, G7283239193, G7903046090, The adipose exposome effects on the plasma metabolome, body composition and metabolic outcomes after bariatric surgery, G8395073261, G8440511448, Southern California Center for Children’s Environmental Health Translational Research, Mount Sinai Center for Health and Environment Across the LifeSpan (HEALS), Sources, Transport, Exposure & Effects of PFAS (STEEP) Center - RENEWAL, G99296377
OpenAlex ID: W4387094757