Integrated multi-endpoint hazard prioritization of unregulated industrial contaminants: A safety-first screening framework for emerging environmental threats

The rapid expansion of the industrial chemical space has outpaced regulatory oversight, creating a critical regulatory and environmental blind spot regarding unregulated high-consequence chemicals with limited hazard characterization. While conventional QSAR models focus on predictive accuracy for known chemicals, they often lack the decision-oriented screening required for environmental risk management. Here, we present a "proactive discovery" framework designed to unveil hidden high-consequence threats among 16,000+ structural analogs of toxic industrial chemicals (TICs). The central contribution of this work is the integration of multiple hazard endpoints, including acute, dermal, ocular, respiratory, flammability, reactivity, and aquatic toxicity, onto a single regulatory-aligned 0-4 scale, rather than the prediction of any individual endpoint. By integrating National Fire Protection…