Pulmonary hazard identifications of Graphene family nanomaterials: Adverse outcome pathways framework based on toxicity mechanisms

Abstract

Graphene-family nanomaterials (GFNs) are revolutionary new nanomaterials that have attracted significant attention in the field of nanomaterials, but the ensuing problems lie in the potential threats to public health and the ecosystem caused by these nanomaterials. From the perspective of GFN-related health risk assessments, this study reviews the current status of GFN-induced pathological lung events with a focus on the damage caused to different biological moieties (molecular, cellular, tissue, and organ) and the mechanistic relationships between different toxic endpoints. These multiple sites of damage were matched with existing adverse outcome pathways (AOPs) in an online knowledge base to obtain available molecular initiation events (MIEs), key events (KEs), and adverse outcomes (AOs). Among them, the MIEs were discussed in combination with the structure-activity relationship due to the correlation between toxicity and physical and chemical properties of GFNs. Based on the collection of information regarding MIEs, Kes, and AOs in addition to upstream and downstream causal extrapolation, the AOP framework for GFN-induced pulmonary toxicity was developed, highlighting the possible mechanisms of GFN-induced lung damage. This review intended to combine AOP with classic toxicological methods with a view to rapidly and accurately establishing a nanotoxicology infrastructure so as to contribute to public health risk assessment strategies through iteration from and animal models up to the population level.

Keywords: Adverse outcome pathway (AOP); Graphene-Family nanomaterial (GFN); Health risk assessment; Nanotoxicology; Pulmonary toxicity.