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 (ERα) agonism, originally derived by Borgert et al. (2018), and confirms that a HRPT of 1 to 10^-1 effectively predicts clinical endometrial and endocervical effects. The research further maps inference performance to ICCVAM's scientific confidence framework (SCF), demonstrating its utility as an initial screening tool before more detailed evaluations. The study concludes that a HRPT for ERα agonism of 10^-2 to 10^-4 is a health-protective new approach methodology (NAM) suitable for early screening, and emphasizes that inference performance is essential for SCFs.