Multiomics Biomarkers of ZnO Nanoparticle Toxicity Using Mitochondrial, Oxidative Stress and Epigenetic Signatures

Zinc oxide nanoparticles (ZnO NPs) rank among the highest-volume engineered nanomaterials, and their partial dissolution generates a composite particle and ion exposure that converges on three measurable molecular layers. This review consolidates quantitative endpoints reported across in vitro, rodent, avian, piscine and controlled human exposures and organises them into mitochondrial, redox and epigenetic signature classes. Reported responses include mitochondrial membrane potential loss to 55 percent of control, mitochondrial DNA copy number shifts spanning 290 percent to 80 percent of control, PGC-1 alpha suppression to 48.6 percent, global 5-methylcytosine reduction to 42 percent, histone G9a induction near 50-fold, and transcriptomic responses reaching 2703 differentially expressed genes. Cross-layer convergence is anchored by zinc homeostasis regulators, heme oxygenase 1, one carbon metabolite accumulation and ferroptotic lipid remodelling across species. A candidate integrated biomarker panel is proposed here together with the analytical and dosimetric constraints that presently limit its regulatory adoption.