Organ-on-a-chip toxicology.

Traditional toxicology, with its reliance on animal models and oversimplified cell cultures, often fails to predict human responses due to interspecies differences and limited physiological relevance. Organ-on-a-chip (OoC) technology, as a microengineering breakthrough, enables reconstruction of human-relevant organ functions, providing a powerful tool for toxicity testing. However, OoC remains largely regarded as a technological platform rather than a distinct research discipline. In this review, we propose organ-on-a-chip toxicology (OCT) as a groundbreaking interdisciplinary paradigm that integrates advanced engineering, toxicological science, and biomedical research to redefine toxicological assessment. OCT transcends conventional OoC technology by providing a unified framework for elucidating toxicity effects and mechanisms at molecular, cellular, and organ levels. It uniquely enables comprehensive systemic toxicity modeling, incorporating full absorption-distribution-metabolism-excretion pathways and inter-organ signaling. Leveraging cutting-edge bioengineering, organoid-driven cellular fidelity, and AI-enhanced data analytics, OCT delivers unparalleled precision in drug safety evaluation, personalized toxicology, environmental hazard assessment, and food health. Despite current challenges in standardization, scalability, and regulatory acceptance, OCT holds the potential to revolutionize toxicological science by offering predictive, ethical, and human-centric insights, minimizing animal testing while advancing global health risk assessments.