The Role of ES&T in Advancing Environmental Toxicology and Chemical Risk Assessment: Past, Present, and Future.

Environmental contamination poses risks to all components of the ecosystem─humans and wildlife─yet toxicological research and regulatory assessment remain largely compartmentalized by discipline and organismal focus. We look back on 60 years of toxicological research published in Environmental Science and Technology (ES&T) and analyze how the field has evolved, what role ES&T has played in this evolution, and suggest a path forward for the future. Chemicals, complex mixtures, and their transformation products act across interconnected biological taxa, including humans, that share conserved molecular and physiological pathways. Integrating ecotoxicology, human toxicology, exposomics, and data-driven new approach methodologies can shift hazard and risk assessment from single-chemical, single-species paradigms toward a mechanism-based, systemic understanding of toxicity across the entire ecosystem. We discuss advances in the characterization of adverse outcome pathways and key biological targets, mixture-oriented testing strategies with effect-based bioassays, and advanced computational approaches. Understanding shared and specific toxicity pathways enables earlier and more reliable detection of potential chemical hazards, strengthens cross-species extrapolation, and supports the development of more predictive and sustainable chemical design and management strategies in the context of the One Health paradigm.