Effects of Bisphenol A and Bisphenol S Exposure at Low Doses on the Metabolome of Adolescent Male Sprague–Dawley Rats

Toxic effects induced upon exposure to low-dose bisphenol A (BPA) or bisphenol S (BPS) remains controversial. In this study, metabolomics was used to examine the metabolomic perturbation arising from 28 days of exposure to BPA or BPS at 50 μg/kg bw/day in Sprague-Dawley (SD) rats. Endogenous metabolite profiling revealed a clear discrimination of metabolome in the rat plasma among BPA-treatment, BPS-treatment, and control groups. BPA exposure induced the up-regulation of 19 metabolites and down-regulation of 32 metabolites in plasma of SD rats, compared with the control. BPS exposure induced the up-regulation of 15 metabolites and the down-regulation of 33 metabolites in the plasma of SD rats, compared with the control. Joint pathway analysis suggested marked perturbations in the citrate cycle, butanoate metabolism, and alanine, aspartate, and glutamate metabolism for BPA-exposed rats as well as glycerophospholipid metabolism for BPS-exposed rats. These findings provide novel insights into associations between the metabolomic perturbation and phenotypic changes arising from BPA and BPS exposure.