Reproduction of the Human Relevant Potency Threshold for Estrogen Receptor Alpha Agonism in an Inference Performance Screen for ICCVAM's Regulatory Scientific Confidence Framework

The study reproduces the Human Relevant Potency Threshold (HRPT) for estrogen receptor alpha agonism, emphasizing its role as a health-protective new approach methodology (NAM) that could reduce animal testing by eliminating the need for further in vivo testing if potency is below the threshold. It highlights the importance of inference performance in scientific confidence frameworks, suggesting it as a core requirement for early screening. The research, involving 305 postmenopausal women, found that oral isoflavones up to 70 mg per day do not cause proliferative or carcinogenic effects on the endometrium. The HRPT of 1 × 10−4 is considered conservative and protective for human health, and the study underscores the need for regulatory frameworks to ensure NAMs are fit-for-purpose.