Bisphenols are frequently used in the plastic industry. However, there is a need for addressing their safety in in vivo studies based on the observed negative impact of bisphenol A. Bisphenol AP (BPAP) is frequently found in the environment, human food, and biological fluids, but its cardiovascular effects have not yet been tested. For this reason, we administered BPAP in a daily single dose of 2.5 mg.kg-1via oral gavage to eight male Wistar Han rats for a period of 4 weeks. Eight control rats received the solvent, sesame oil. Parent BPAP was detectable in plasma only in 3 animals by a validated LC-MS/MS method, whereas its glucuronide was found in all animals (48.4 ± 25.4 nM). Arterial blood pressure did not change during or at the end of the treatment. Some disturbances in cardiac rhythm were observed (e.g., increased heart rate, prolonged P wave and QTpeak interval, p < 0.05), but there was no increase in serum cardiac troponin T. Vessels isolated from BPAP-treated animals showed impaired vasodilatory response compared to control animals (p < 0.05). BPAP impacted coagulation and caused hemolysis only in hundreds of µM concentrations. These results demonstrate the potential of BPAP to affect cardiac rhythm and impair vessel homeostasis after subacute exposure.

Charles University Faculty of Pharmacy The Department of Pharmacognosy and Pharmaceutical Botany Akademika Heyrovského 1203 Hradec Králové 500 03 Czech Republic

Charles University Faculty of Pharmacy The Department of Pharmacology and Toxicology Akademika Heyrovského 1203 Hradec Králové 500 03 Czech Republic

Charles University Faculty of Pharmacy The Department of Pharmacology and Toxicology Akademika Heyrovského 1203 Hradec Králové 500 03 Czech Republic; The Ohio State University Pelotonia Research Center Division of Outcomes and Translational Sciences 2255 Kenny Rd Columbus OH USA

University of Ljubljana Faculty of Pharmacy Aškerčeva cesta 7 Ljubljana 1000 Slovenia

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