Predicting Skin Irritation, Corrosion, and Sensitization Potential of Nanomaterials Using OECD-Validated New Approach Methodologies (NAMs)

Abstract

Nanomaterials are increasingly used in consumer and industrial products, creating a need for comprehensive and reliable safety evaluations. Current standardised methods developed by the Organisation for Economic Co-operation and Development (OECD) have yet to be fully validated for the assessment of nanomaterials. This study systematically investigated the skin irritation, corrosion, and sensitisation potential of five industrially relevant nanoparticles (NPs): titanium dioxide (TiO₂), zinc oxide (ZnO), nickel oxide (NiO), silver (Ag), and polystyrene (PS), using OECD-validated in vitro models and the Integrated Approach to Testing and Assessment (IATA). The reliability of OECD Test Guidelines (TGs) 439 and 431 for assessing nanomaterials-induced skin irritation and corrosion was confirmed, with results integrated using the IATA framework as outlined in OECD Guidance Document 203. However, skin sensitisation assays, including KeratinoSens™ (TG 442D), the human Cell Line Activation Test (h-CLAT, TG 442E), and the Defined Approaches (Guideline 497), produced conflicting or inconclusive results for certain metal-based NPs such as TiO₂ and NiO, while Ag NPs consistently tested positive across multiple assays. The 3D reconstructed human epidermis (RHE) model for skin irritation and corrosion testing minimised assay interference and provided a more physiologically relevant representation of the skin barrier compared with conventional 2D cultures used in skin sensitisation assays. This study highlights the applications and limitations of existing OECD TGs and current in vitro approaches for evaluating potential skin toxicities of metal-based NPs. By identifying current gaps, it supports refinement of reliable, standardised non-animal testing strategies and informs future adaptation of regulatory guidelines for improved nanomaterial safety assessment.