From exposure to risk prevention: an integrated, data driven approach to testing and assessing occupational hazards...

Occupational risk assessment of manufactured nanomaterials (MNMs) requires targeted hazard and exposure quantification, which, however, are currently limited by uncertainties about measurements and metrics. Integrated approaches to testing and assessment (IATAs) emerge as efficient tools to streamline the risk assessment of MNMs. This study formulates an Occupational Hazard IATA (OH IATA) to identify and quantify the hazard of involuntarily inhaled MNMs in workplaces. Following general IATA guidance, key toxicity events (KTEs) relevant to inhaled MNMs, such as deposition, accumulation, local or systemic inflammation, and genotoxicity, were identified and incorporated into decision nodes (DNs) within the OH IATA framework. The OH IATA is structured as a decision tree enabling tiered testing strategies, from in vitro to in vivo, to generate evidence addressing the DNs. Hazard profiles are categorized into bands labeled from A (no risk) to E (serious hazard), following ISO control banding principles and including new criteria focusing on key physicochemical descriptors like deposition and dissolution in synthetic biological fluids. The OH IATA was evaluated using industrial case studies such as few-layer graphene (FLG) and graphene oxide (GO), applying a hybrid data-gathering approach that combines next-generation and literature-based data. The results demonstrated that OH IATA successfully assigned hazard bands to the tested MNMs and supported the identification of appropriate control measures. Innovative methods, such as in vitro dissolution quantification in simulant fluids, contributed to the high predictivity of the hazard assessment. The OH IATA, integrated with multiparametric exposure testing within the broader "Prevention-through-Design, NanoKey" framework, provides a targeted, data-driven strategy for the assessment and prevention of risks associated with inhaled MNMs in occupational settings. This approach enhances workplace safety, supports regulatory compliance, and promotes long-term sustainability in nanomaterial-based industries.