Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
5080564
Reference Type
Journal Article
Title
Characterization of non-radiolabeled Thyroxine (T4) uptake in cryopreserved rat hepatocyte suspensions: Pharmacokinetic implications for PFOA and PFOS chemical exposure
Author(s)
Selano, J; Richardson, V; Washington, J; Mazur, C
Year
2019
Is Peer Reviewed?
1
Journal
Toxicology In Vitro
ISSN:
0887-2333
EISSN:
1879-3177
Volume
58
Page Numbers
230-238
Language
English
PMID
30930230
DOI
10.1016/j.tiv.2019.03.022
Web of Science Id
WOS:000472589900026
URL
https://linkinghub.elsevier.com/retrieve/pii/S0887233318306787
Exit
Abstract
The alteration of thyroxine (T4) cellular uptake by an environmental chemical can serve as a contributing factor in thyroid hormone (TH) disruption. Herein, we describe a non-radiolabeled (LC-MS/MS) oil-filtration technique designed to characterize the mechanism(s) responsible for T4 cellular uptake in cryopreserved rat hepatocyte suspensions. The environmental chemicals perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) were evaluated for their effect on T4 hepatic uptake. At 37 °C, hepatic assays demonstrated saturable kinetics with increasing T4 concentrations, while a linear uptake rate consistent with passive diffusion was detected at 4 °C. Carrier-mediated (37-4 °C) transport of T4 was the predominant hepatic uptake process versus passive diffusion. Cyclosporin A (CsA) chemically inhibited T4 hepatic uptake, whereas PFOA/PFOS displayed no inhibition of T4 translocation. Increasing PFOA/PFOS concentration levels with the T4 serum carrier-protein transthyretin (TTR) present resulted in a dose-response increase in T4 hepatic uptake rates, correlating with increased T4 free fraction values. Hepatic assays conducted in the presence of PFOA/PFOS and TTR displayed an enhanced first-order T4 hepatic uptake rate consistent with carrier-mediated transport. These in vitro findings characterizing increased T4 hepatic uptake provides mechanistic insight regarding decreased T4 serum levels (hypothyroxinemia) previously observed within in vivo rodent studies following perfluorinated chemical exposure.
Keywords
Hepatic uptake; Thyroid hormone; Transport; Pharmacokinetics
Tags
PFAS
•
Additional PFAS (formerly XAgency)
•
Expanded PFAS SEM (formerly PFAS 430)
Litsearch: September 2019
PubMed
Web of Science
Not prioritized for screening
Perfluorooctane
•
PFAS 150
Literature Search Update December 2020
PubMed
WOS
Literature Search August 2019
PubMed
Web of Science
Other sources
Reference list review of included studies
Not prioritized for screening
Perfluorooctane
Perfluorooctanesulfonic acid
•
PFHxS
•
PFOA (335-67-1) and PFOS (1763-23-1)
Literature Search Update (2013-2019)
PubMed
•
Yale PFAS Liver study
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity