Safety analysis of engineered nanomaterials (ENMs) presents a formidable challenge regarding environmental health and safety,due to their complicated and diverse physicochemical properties.Although large amounts of data have been published regarding the potential hazards of these materials,we still lack a comprehensive strategy for their safety assessment,which generates a huge workload in decision-making.Thus,an integrated approach is urgently required by govment,industry,academia and all others who deal with the safe implementation of nanomaterials on their way to the marketplace.The rapid emergence and sheer number of new nanomaterials with novel properties demands rapid and high-content screening (HCS),which could be performed on multiple materials to assess their safety and generate large data sets for integrated decision-making.With this approach,we have to consider reducing and replacing the commonly used rodent models,which are expensive,time-consuming,and not amenable to high-throughput screening and analysis.In this review,we present a’Library Integration Approach’for high-content safety analysis relevant to the ENMs.We propose the integration of compositional and property-based ENM libraries for HCS of cells and biologically relevant organisms to be screened for mechanistic biomarkers that can be used to generate data for HCS and decision analysis.This systematic approach integrates the use of material and biological libraries,automated HCS and high-content data analysis to provide predictions about the environmental impact of large numbers of ENMs in various categories.This integrated approach also allows the safer design of ENMs,which is relevant to the implementation of nanotechnology solutions in the pharmaceutical industry.