TY - JOUR
T1 - Unbound Fractions of PFAS in Human and Rodent Tissues
T2 - Rat Liver a Suitable Proxy for Evaluating Emerging PFAS?
AU - Ryu, Sangwoo
AU - Burchett, Woodrow
AU - Zhang, Sam
AU - Jia, Xuelian
AU - Modaresi, Seyed Mohamad Sadegh
AU - Agudelo Areiza, Juliana
AU - Rodrigues, David
AU - Zhu, Hao
AU - Sunderland, Elsie M.
AU - Fischer, Fabian Christoph
AU - Slitt, Angela L.
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/8/20
Y1 - 2024/8/20
N2 - Adverse health effects associated with exposures to perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a concern for public health and are driven by their elimination half-lives and accumulation in specific tissues. However, data on PFAS binding in human tissues are limited. Accumulation of PFAS in human tissues has been linked to interactions with specific proteins and lipids in target organs. Additional data on PFAS binding and unbound fractions (funbound) in whole human tissues are urgently needed. Here, we address this gap by using rapid equilibrium dialysis to measure the binding and funbound of 16 PFAS with 3 to 13 perfluorinated carbon atoms (ηpfc = 3-13) and several functional headgroups in human liver, lung, kidney, heart, and brain tissue. We compare results to mouse (C57BL/6 and CD-1) and rat tissues. Results show that funbound decreases with increasing fluorinated carbon chain length and hydrophobicity. Among human tissues, PFAS binding was generally greatest in brain > liver ≈ kidneys ≈ heart > lungs. A correlation analysis among human and rodent tissues identified rat liver as a suitable surrogate for predicting funbound for PFAS in human tissues (R2 ≥ 0.98). The funbound data resulting from this work and the rat liver prediction method offer input parameters and tools for toxicokinetic models for legacy and emerging PFAS.
AB - Adverse health effects associated with exposures to perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a concern for public health and are driven by their elimination half-lives and accumulation in specific tissues. However, data on PFAS binding in human tissues are limited. Accumulation of PFAS in human tissues has been linked to interactions with specific proteins and lipids in target organs. Additional data on PFAS binding and unbound fractions (funbound) in whole human tissues are urgently needed. Here, we address this gap by using rapid equilibrium dialysis to measure the binding and funbound of 16 PFAS with 3 to 13 perfluorinated carbon atoms (ηpfc = 3-13) and several functional headgroups in human liver, lung, kidney, heart, and brain tissue. We compare results to mouse (C57BL/6 and CD-1) and rat tissues. Results show that funbound decreases with increasing fluorinated carbon chain length and hydrophobicity. Among human tissues, PFAS binding was generally greatest in brain > liver ≈ kidneys ≈ heart > lungs. A correlation analysis among human and rodent tissues identified rat liver as a suitable surrogate for predicting funbound for PFAS in human tissues (R2 ≥ 0.98). The funbound data resulting from this work and the rat liver prediction method offer input parameters and tools for toxicokinetic models for legacy and emerging PFAS.
UR - https://www.scopus.com/pages/publications/85200817289
UR - https://www.scopus.com/pages/publications/85200817289#tab=citedBy
U2 - 10.1021/acs.est.4c04050
DO - 10.1021/acs.est.4c04050
M3 - Article
C2 - 39161261
AN - SCOPUS:85200817289
SN - 0013-936X
VL - 58
SP - 14641
EP - 14650
JO - Environmental Science and Technology
JF - Environmental Science and Technology
IS - 33
ER -