A Scoping Assessment of Implemented Toxicokinetic Models of Per- and Polyfluoro-Alkyl Substances, with a Focus on One-Compartment Models

Abstract

Toxicokinetic (TK) models have been used for decades to estimate concentrations of per-and polyfluoroalkyl substances (PFAS) in serum. However, model complexity has varied across studies depending on the application and the state of the science. This scoping effort seeks to systematically map the current landscape of PFAS TK models by categorizing different trends and similarities across model type, PFAS, and use scenario. A literature review using Web of Science and SWIFT-Review was used to identify TK models used for PFAS. The assessment covered publications from 2005–2020. PFOA, the PFAS for which most models were designed, was included in 69 of the 92 papers, followed by PFOS with 60, PFHxS with 22, and PFNA with 15. Only 4 of the 92 papers did not include analysis of PFOA, PFOS, PFNA, or PFHxS. Within the corpus, 50 papers contained a one-compartment model, 17 two-compartment models were found, and 33 used physiologically based pharmacokinetic (PBTK) models. The scoping assessment suggests that scientific interest has centered around two chemicals—PFOA and PFOS—and most analyses use one-compartment models in human exposure scenarios.

Occurrence of Major Perfluorinated Alkylate Substances in Human Blood and Target Organs

“…PBTK modeling has been used to describe the body distribution of PFASs in mammals, 12 but their applicability to human exposure is currently limited due to missing toxicokinetic parameters, such as permeabilities, transport affinities, and elimination constants. 13 As a simplified alternative, equilibrium distribution modeling (EDM) can predict the distribution of PFASs based on the protein, lipid, and water content of various human organs. 14 Comparing EDM simulations to PFAS concentrations observed in human organs could offer valuable insights into whether organ binding primarily drives the overall organ distribution or if kinetic processes need to be accounted for in more complex PBTK models (e.g., enterohepatic recirculation and renal reabsorption).…”

“…PBTK modeling has been used to describe the body distribution of PFASs in mammals, but their applicability to human exposure is currently limited due to missing toxicokinetic parameters, such as permeabilities, transport affinities, and elimination constants . As a simplified alternative, equilibrium distribution modeling (EDM) can predict the distribution of PFASs based on the protein, lipid, and water content of various human organs .…”