Disposition of Bisphenol S metabolites in Sprague-Dawley rats

Bisphenol S (BPS), a primary bisphenol A (BPA) substitute, has shown a comparable estrogenic activity to BPA. To comprehensively evaluate the toxic effect of human BPS exposure, it is necessary to understand the occurrence of free BPS and its conjugated metabolites in human internal tissues, but which remains unclear. In this study, Sprague-Dawley rats were orally and continuously dosed at 500 μg/kg/day to mimic the actual human BPS exposure scenario, and then free BPS and its conjugated metabolites were analyzed in rat internal tissues, blood, and excreta. Results showed that concentrations of free BPS and its metabolites in most rat tissues, excreta, and blood reached the steady state after 9 days of continuous BPS dosage. In rat urine, 81-84% of BPS was present in the conjugated form, with BPS glucuronide (BPS-G) and BPS sulfate (BPS-S) accounting for mean 83% and 16% of total conjugated BPS, respectively. In rat blood, mean 55% of total BPS was present in the conjugated form, with BPS-G (2.4-2.8 ng/mL) being more abundant than BPS-S (0.19-0.25 ng/mL). Among rat tissues, the mean proportion of free BPS was relatively higher in spleen (76%) and stomach (75%), while lower in intestine (14%) and kidney (36%). BPS-G was more abundant than BPS-S in most rat tissues, such as intestine (mean 93% versus 6.5%) and muscle (78% versus 19%). While, the mean proportion of BPS-S (48%) was higher than BPS-G (33%) in rat liver. These data suggest that analyzing human blood and urine may not accurately reflect the contamination of BPS metabolites in human internal tissues. This study contributes to the better understanding of the metabolic fate of BPS in humans.