Engineered Nanoparticles (ENPs) of silica, ceria and alumina are used as polishing slurries for Chemical Mechanical Planarization (CMP). However, the regulations for use and toxic levels of ENPs in slurries are yet to be established. The objective of this work is to study and compare the cellular toxicity, uptake and environmental discharge levels of the CMP nanoparticle slurries before and after the CMP process and to formulate threshold levels of toxicity, namely half maximal inhibitory concentration (IC50). IC50 value is a measure that represents the effectiveness of a substance in inhibiting 50% of specific biological/biochemical function. ENPs’ reactivity along with their cellular toxicity and uptake are largely dependent on their physicochemical characteristics. This paper will also present the correlation between physicochemical properties of ENPs and toxicity level so as to design and develop benign CMP ENPs. The current study will present a comparison between pre- and post-CMP slurries containing colloidal silica, fumed silica and ceria ENPs. Post-CMP slurry waste were generated by polishing patterned test wafers of HDP oxide and copper (MIT 864 and MIT 854) for 2, 4, 6, 8 and 10 minutes on IPEC Avanti 472 CMP tool. First, pre- and post-CMP slurries and waste were comprehensively characterized using DLS, zeta potential, BET, XRD, FTIR, Raman, SEM and TEM. Next, slurries and waste were exposed to A549 lung epithetical cell lines for 6-48 hours to determine IC50 for cytotoxicity (cell viability and membrane integrity). It was observed that colloidal and fumed silica ENPs in slurries showed dose- and time-dependent IC50 for cytotoxicity. Next, using label-free analytical techniques such as confocal Raman and ICP spectroscopy, we observed that pre- and post-CMP ceria ENPs in slurries, exhibited dose-dependent uptake in A549 cells. Lastly, we studied the waste discharge to understand the constitution and concentration of various elemental species, ions and organic materials in environmental discharge.