Integrated approaches to testing and assessment for the endocrine disrupting activity of tartrazine based on adverse...

Tartrazine (TTZ), a widely used synthetic azo dye in processed foods, beverages, and pharmaceuticals, raises various health concerns including hematotoxicity, genotoxicity, carcinogenicity, neurotoxicity, and endocrine activity. Regarding the endocrine disruption, although individual studies has reported estrogenic, androgenic and thyroid effects, a comprehensive and integrated evaluation of across hormonal systems have never been tried. To address this gap, we performed multi-tool in silico approaches covering all nuclear receptors. Docking simulations (Endocrine Disruptome, CB-Dock2, and AutoDock Vina) were employed to estimate receptor-binding propensities. Machine learning-based resources (ADMETlab3.0, ProTox-3.0, CERAPP/CoMPARA, and EDC-Predictor) were used to forecast endocrine activities. Most nuclear receptors exhibited potential effects by TTZ-including AR, ERα, TRα/β, PXR, RXRα, PPARγ, and AhR-except ERβ. Consistently, ToxCast reported active calls for AR, ERα, TR, RXR, and AhR. In addition, SwissTargetPrediction and PharmMapper indicated that TTZ could predominantly influence reproductive and thyroid toxicity via cancer-related pathways. We further aligned in silico outputs with existing in vitro and in vivo findings mapped to AOPs for the estrogen, androgen, and thyroid axes, and summarized evidence across hormonal systems under OECD-relevant considerations to clarify current knowledge and guide future systematic endocrine profiling of TTZ.