The goal of PrecisionTox is to advance safety assessment of chemicals without the use of animal testing by establishing a new, 3Rs-compliant, cost-effective testing paradigm for chemical safety assessment — Precision Toxicology — that identifies molecular key event (KE) biomarkers predictive of chemically induced adverse health effects in humans and facilitates their uptake into regulatory and industry practice. This goal is supported by three core concepts: PhyloToxicology, which replaces mammal models with an evolutionarily diverse suite of non-sentient animal species from across the tree of life; Quantitative Susceptibility, which determines safety factors based on genetic variability; and Embedded Translation, which engages key stakeholders in project planning, selection of chemicals for investigation, and case studies for regulatory application. We accomplish this goal through six objectives: ● Stakeholder Integration, embedding the Stakeholder Advisory Group in project management (WP1); ● Comparative Toxicology, utilising high-throughput testing methods across five non-sentient species and human cell lines to observe toxic response (WP2); ● Molecular Data Production, applying metabolomics and transcriptomics to comparative toxicology samples to trace adverse outcomes via the molecular key events preceding them (WP3); ● Quantitative Susceptibility, applying quantitative genetics and gene expression profiling to understand variation in individual susceptibility and develop empirical exposure thresholds (WP4); ● Biomarker Discovery, PrecisionTox Data Commons, and NAM Toolbox, using machine learning to identify biomarkers for molecular key events and creating the dissemination and translation products for their use (WP5); and ● Regulatory Analysis and Application, partnering with JRC and regulatory agencies to identify opportunities for applying Precision Toxicology within existing regulatory structures and develop draft guidance for industry use and reporting (WP6).