# Endocrine Disruptors and  Heart Health

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2022 · $351,980

## Abstract

Bisphenol A (BPA) is a common environmental endocrine disrupting chemical (EDC) with a range of
potential adverse health effects. Growing epidemiologic and experimental studies have demonstrated a
potential link between higher BPA exposure and cardiovascular diseases. In previous studies, we reported
some of the first evidence on the arrhythmogenic actions of BPA in rodent hearts. We further showed that the
pro-arrhythmic effects of BPA was shared by bisphenol S (BPS), a BPA analog that is used in many of the
“BPA-free” products. Our findings demonstrate the potential pro-arrhythmic toxicity of BPA, and highlight the
need to further define the impact of BPA and related EDCs on human heart health.
 The goal of our proposal is to determine the pro-arrhythmic toxicity of BPA and BPS in larger animals,
including humans, particularly through prolongation of the QT interval of the electrocardiogram (ECG). QT
interval reflects the duration of ventricular excitation of the heart. In human and other larger species, a distinct
arrhythmogenic mechanism is QT prolongation. Importantly, QT prolongation is a common forms of cardiac
toxicity for chemical and pharmaceutical agents, and is well recognized as a central issue in cardiac safety.
 It has been shown that female sex hormones, including estrogen, prolong QT interval in both human
females and animal models. However, the impact of BPA, a near ubiquitous estrogenic EDC, on the risk of QT
prolongation and related arrhythmias is entirely unknown. Supported by compelling preliminary studies, we
propose to address the central hypothesis that in the hearts of larger species including human, low-dose BPA
and BPS have pro-arrhythmic toxicity through delay of ventricular repolarization and prolongation of the QT
interval; this pro-arrhythmic action is particularly significant in hearts with existing QT prolongation, such as
those of idiopathic long QT syndrome (LQT) patients.
 The study uses a combination of animal experiments using rabbits, and epidemiology analysis using
biospecimens and data from the Fernald Community Cohort. The gender-specificity of the actions of the
bisphenol chemicals will be addressed in each Aim. Three aims are proposed. The long-term (Aim 1) and rapid
(Aim 2) effects of BPA and BPS exposure on cardiac electrophysiology and arrhythmogenesis will be
examined using the rabbit model. In Aim 3, the correlation of BPA exposure in human adults and ECG markers
of cardiac electrical abnormalities will be examined in the Fernald Community Cohort. The proposed research
is significant because it is expected to provide important insights into the action and underlying mechanism of
BPA and BPS on larger animal hearts. Further, our study will provide better understanding of the risk factors of
cardiac arrhythmia, particularly in vulnerable subpopulations with cardiac disease. The Fernald Cohort study
represents the first epidemiologic study on the association between BPA exposure and cardiac electrica...

## Key facts

- **NIH application ID:** 10330458
- **Project number:** 5R01ES027855-05
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Jack Rubinstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $351,980
- **Award type:** 5
- **Project period:** 2018-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330458

## Citation

> US National Institutes of Health, RePORTER application 10330458, Endocrine Disruptors and  Heart Health (5R01ES027855-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10330458. Licensed CC0.

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