2026 CONVENTION
An AOP-informed integrated approaches to testing and assessment (IATA) study of estrogenic activity in consumer product chemicals
The endocrine-disrupting chemicals in consumer products remains insufficiently characterized using integrated mechanistic approaches. Here, we applied an adverse outcome pathway (AOP)-informed Integrated Approaches to Testing and Assessment (IATA) framework to evaluate the estrogenic activity of fourteen representative chemicals by combining computational and in vitro evidence. The strategy integrated in silico ERα-binding predictions with an ERα transactivation assay (OECD TG 455) and an H295R steroidogenesis assay (OECD TG 456), covering molecular initiating events and downstream key events. In silico models predicted moderate ERα binding but showed limited concordance, highlighting the need for experimental confirmation. In the ERα transactivation assay, thirteen of fourteen compounds showed estrogenic activity based on PC10 values. Among selected high-response compounds, benzisothiazolinone and propyl paraben increased estradiol production and upregulated key steroidogenic regulators, whereas other compounds mainly exhibited receptor-mediated activity without corresponding steroidogenic effects. Overall, integration of these evidence streams enabled mechanistic differentiation of estrogenic responses and improved prioritization beyond reliance on a single assay or prediction model, supporting the use of AOP-informed IATA for mechanism-based assessment of consumer product chemicals.