Meta-analysis of in-vitro cytotoxicity evaluation studies of zinc oxide nanoparticles: Paving way for safer innovations

Nano-based products have shown their daunting presence in several sectors. Among them, Zinc Oxide (ZnO) nanoparticles wangled the reputation of providing "next-generation solutions" and are being utilized in plethora of products. Their widespread application has led to increased exposure of these particles, raising concerns regarding toxicological repercussions to the human health and environment. The diversity, complexity, and heterogeneity in the available literature, along with correlation of befitting attributes, makes it challenging to develop one systematic framework to predict this toxicity. The present study aims at developing predictive modelling framework to tap the prospective features responsible for causing cytotoxicity in-vitro on exposure to ZnO nanoparticles. Rigorous approach was used to mine the information from complete body of evidence published to date. The attributes, features and experimental conditions were systematically extracted to unmask the effect of varied features. 1240 data points from 76 publications were obtained, containing 14 qualitative and quantitative attributes, including physiochemical properties of nanoparticles, cell culture and experimental parameters to perform meta-analysis. For the first time, the efforts were made to investigate the degree of significance of attributes accountable for causing cytotoxicity on exposure to ZnO nanoparticles. We show that in-vitro cytotoxicity is closely related with dose concentration of nanoparticles, followed by exposure time, disease state of the cell line and size of these nanoparticles among other attributes.