Bisphenol S and Bisphenol F Are Less Disruptive to Cardiac Electrophysiology, as Compared With Bisphenol A.
Level 5 - mechanism / opinion, no new human data
Preclinical bench and ex vivo animal research (cell lines, hiPSC-CMs, and isolated rat hearts)
PubMed 34240201 · doi:10.1093/toxsci/kfab083
What was done
Researchers compared the direct electrophysiological effects of bisphenol A (BPA) with its structural replacement analogs, bisphenol S (BPS) and bisphenol F (BPF). They performed whole-cell voltage-clamp recordings on transfected cell lines expressing Nav1.5 (sodium), Cav1.2 (L-type calcium), and hERG (potassium) channels. They also evaluated extracellular field potentials in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using microelectrode arrays and assessed conduction parameters in intact, isolated rat heart preparations.
What was found
BPA was the most potent ion channel blocker, inhibiting peak sodium current (IC50 = 55.3 µM), late sodium current (IC50 = 23.6 µM), L-type calcium current (IC50 = 30.8 µM), and hERG current (IC50 = 127 µM), while shortening the extracellular field potential in hiPSC-CMs. In isolated rat hearts, BPA dose-dependently slowed atrioventricular (AV) conduction and increased AV node refractoriness (+9.2% at 0.001 µM; +95.7% at 100 µM). BPF also slowed AV conduction (+20.7% at 100 µM). BPS did not alter any of the cardiac electrophysiological parameters tested.
Why it matters
As industrial and consumer manufacturing seeks replacements for BPA, these findings suggest that BPS may be substantially less disruptive to acute cardiac electrophysiology and ion channel function than BPA or BPF.
Limits
All findings derive from in vitro cell models, stem cell-derived cardiomyocytes, and ex vivo rodent heart preparations, precluding direct assessment of human in vivo toxicity, chronic exposure, or complex pharmacokinetics. Specific sample sizes (n) and statistical uncertainty intervals were not reported in the abstract.
Cited by
- supports Acute exposure to BPA inhibits voltage-gated calcium channels in cardiomyocytes, impairing calcium handling and heart contractions.