Effects of Bisphenol A on Incidence and Severity of Cardiac Lesions in the NCTR-Sprague-Dawley Rat: A CLARITY-BPA Study

Abstract

The goal of this study was to determine whether bisphenol A (BPA) had adverse effects indicative of cardiac toxicity. As part of the \"Consortium Linking Academic and Regulatory Insights on BPA Toxicity\" (CLARITY-BPA), study dams and offspring were exposed by daily gavage to five doses of BPA ranging from 2.5 to 25000 g/kg/day, 0.05 or 0.5 g/kg/day 17-ethinyl-estradiol (EE) or 0.3% carboxymethylcellulose vehicle. Exposure-related effects were analyzed in isolated hearts by quantitative morphometry and histopathology. No dose-related changes in body weight were detected. Across all exposure groups including vehicle controls, body weight of continuously dosed males was reduced compared to males dosed only until PND21. Heart weight was increased only in females exposed to EE, and consistent alterations in LV wall thickness were not observed. Exposure-related changes in collagen accumulation were minor and limited to highest EE exposure groups with increased collagen accumulation in PND21 males. Decreased collagen was observed in hearts of BPA or EE exposed females at PND90 and PND180. In BPA or EE treated females cardiomyopathy incidence and severity was significantly increased compared to control females at PND21 with myocardial degeneration observed in both males and females at PND21 and PND90.