Tuning parameters QExactive Plus. Table S2. Cell numbers [x106] for Control (C) as well as CuO NP Treated (T). Table S3. Cell numbers [x106] of Control (C), STS treated (STS) and Camptothecin treated (CPT) for the different time points. Table S4. Relative standard deviation (RSD) of internal standards for metabolomics profiling – values for Ethylparabene and Nitrotyrosine in CuO NP profiling. Table S5. Feature number after the different steps of data processing. Figure S1. Overlaps at feature level for RP and HILIC separation for (a) positive ESI-mode and (b) negative ESI-mode. Figure S2. Cell viability, cytotoxicity, and IL-8 secretion in response to CuO NPs and Cl2Cu•2H2O. Table S6. Differentially regulated metabolites upon CuO NP treatment. Table S7. Number of differentially expressed features found for each separation method (reversed phase as well as hydrophilic interaction chromatography in positive and negative modes). Figure S3. HO-1 gene expression in response to CuO NPs. Figure S4. GPX1 gene expression in response to CuO NPs. Figure S5. Bar plot of peak areas for Methylnicotinamide at the time points (0 h, 6 h, 12 h and 24 h) of both metabolomics studies CuO NP (control CuO study and CuO treatment) and apoptosis study (control apoptosis study, STS treatment and CPT treatment). (DOCX 193 kb)