Study Summary for:
TEX-VAL-TOX-2024-09-04-PFAS Renal Clearance_TERT-OAT1_2D

Description

This study evaluated the cellular uptake and cytotoxicity of 23 compounds in TERT1-OAT1 RPTECs (human renal proximal tubule epithelial cells). Cells were cultured to confluency in a 96-well plate (6 days) before exposure to the test compounds. Media samples were collected at 4 and 24 hours, and cell lysates were collected at 24 hours. LDH assays assessed cytotoxicity, while LC-MS/MS measured compound accumulation.

Treatments:
Tobramycin (1mM)
Streptomycin (1mM)
Gentamicin (1mM)
Rifampin (10uM)
Indomethacin (10uM)
Tenofovir (TFV, 10uM)
Colchicine (10uM)
PFHxA (5uM)
PFBA (5uM)
PFBS (5uM)
PFHpA (5uM)
PFNA (5uM)
PFOS (5uM)
PFOA (5uM)
PFHxS (5uM)
PFUnDA (5uM)
PFDA (5uM)
4:2 FTS (5uM)
8:2 FTS (5uM)
PFPeA (5uM)
6:2 FTS (5uM)
TAB (50uM), positive control
BP4 (10uM)

Conclusions:
--Exposure concentrations were sub-cytotoxic, allowing for transport assessment without inducing cellular stress.
--RPTECs accumulated PFNA, PFOS, PFDA, 8:2 FTS, and PFUnDA in significant amounts, while other compounds exhibited faster clearance.
--This 96-well RPTEC model may serve as a valuable screening tool for distinguishing between fast- and slow-clearing renal compounds.
--Results closely mirrored those from the previous TERT1-parental RPTEC study, except for tenofovir, which showed significantly higher accumulation in TERT1-OAT1 cells. This aligns with tenofovir being a known substrate for the OAT1 transporter.

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