Toxic Alerts of Endocrine Disruption Revealed by Explainable Artificial Intelligence

Abstract

The local interpretable model-agnostic explanation method was used to unveil substructures (toxic alerts) that cause endocrine disruption in chemical compounds using machine learning models. The random forest classifier was applied to build explainable models with the TOX21 data sets after data curation. Using these models applied to the EDC and EDKB-FDA data sets, the substructures that cause endocrine disruption in chemical compounds were unveiled, providing stable, more specific, and consistent explanations, which are essential for trust and acceptance of the findings, mainly due to the difficulty of finding relevant experimental evidence for different receptors (androgen, estrogen, aryl hydrocarbon, aromatase, and peroxisome proliferator-activated receptors). This approach is significant because of its contribution to the interpretability of explainable machine learning algorithms, particularly in the context of unveiling substructures associated with endocrine disruption in five targets (androgen receptor, estrogen receptor, aryl hydrocarbon receptors, aromatase receptors, and peroxisome proliferator-activated receptors), thereby advancing the relevant field of environmental toxicology, where a careful evaluation of the potential risks of exposure to new compounds is needed. The specific substructures thiophosphate, sulfamate, anilide, carbamate, sulfamide, and thiocyanate are presented as toxic alerts that cause endocrine disruption to better understand their potential risks and adverse effects on human health and the environment.