P30-61 Development of a Novel In vivo Imaging-Based Screening Method to Assess Low-Dose Estrogenic Activity of Bisphenol A

Bisphenol A (BPA) has been widely used in the production of polycarbonate plastics and has been reported to exhibit endocrine-disrupting effects through estrogenic activity in animals. There is growing concern that BPA may exert adverse effects at low doses, potentially below the no-observed-adverse-effect level (NOAEL). However, such low-dose effects are often undetectable by standard toxicity tests, including the uterotrophic bioassay, which is considered the “gold standard” in vivo screening method for assessing estrogenic activity. As a result, the authenticity and significance of these effects remain unclear, and the debate continues. In this study, we developed a novel, highly sensitive, and short-term in vivo screening method for estrogen-like chemicals using in vivo bioluminescence imaging of our estrogen-responsive reporter (E-Rep) mice, previously developed for detecting estrogenic activity 1 , 2 . Comparative studies using 17α-ethinylestradiol, a reference estrogen, and bazedoxifene acetate, a selective estrogen receptor modulator, demonstrated that our method provides higher detection sensitivity and requires less time than the uterotrophic bioassay. Notably, our method successfully detected the estrogenic effects of BPA at doses below the tolerable daily intake (TDI), which were undetectable by the uterotrophic bioassay. These findings suggest that in vivo bioluminescence imaging using our E-Rep mice is a powerful tool for screening estrogenic chemicals and identifying low-dose estrogenic effects of endocrine-disrupting chemicals (EDCs), including BPA. This method may contribute significantly to resolving the ongoing controversy surrounding the low-dose effects of EDCs.