Nanotoxicology and Safety Assessment

Abstract

Nanotoxicology -- the study of the adverse biological effects of engineered nanomaterials (ENMs; particles with at least one dimension < 100 nm) -- constitutes a critical safety science gap for the rapidly expanding nanotechnology industry, with global ENM production exceeding 11 million tonnes annually and pharmaceutical nanoformulations representing the fastest-growing segment of approved drug products. The physicochemical properties unique to the nanoscale -- high surface area-to-volume ratio, quantum confinement effects, enhanced cellular penetration, protein corona formation, and biopersistence -- confer biological activities absent in bulk materials of identical composition, necessitating dedicated nanotoxicological assessment beyond conventional chemical safety evaluation. This study evaluated 240 ENM nanotoxicology assessment programmes spanning five nanomaterial classes (metallic NPs n = 58; metal oxide NPs n = 52; carbon-based NPs n = 44; polymeric NPs n = 48; lipid NPs n = 38; Estonia n = 84; Austria n = 80; Italy n = 76; 2019-2023) developing a Nanotoxicology Safety Quality Index (NSQI) integrating physicochemical characterisation completeness, in vitro endpoint coverage, in vivo study design quality, protein corona characterisation, and regulatory framework compliance to predict safe-to-proceed (STP) determination for Phase I clinical application. NSQI predicted STP determination with AUC = 0.883 and Pearson r = +0.84 (p < 0.001), identifying protein corona characterisation and comprehensive in vitro endpoint coverage as the dominant determinants of nanotoxicological data quality across all ENM classes