This article reviews recent progress from our laboratory in electrochemiluminescence (ECL) arrays designed for screening toxicity-related chemistry of chemical and drug candidates. Cytochrome P450s and metabolic bioconjugation enzymes convert lipophilic chemicals in our bodies by oxidation and bioconjugation that can lead to toxic metabolites. DNA can be used as an easily measurable toxicity-related endpoint, targeting DNA oxidation and addcut formation with metabolites. ECL using guanosines in the DNA strands as co-reactants have been used in high throughput arrays utilizing DNA-enzyme films fabricated layer-by-layer. This review describes approaches developed to provide new high throughput ECL arrays to aid in toxicity assessment for drug and chemical product development.