Nanotoxicology and Adverse Outcome Pathway Modeling

Nanotoxicology investigates the interactions between engineered nanomaterials and biological systems, aiming to characterise how unique nanoscale properties influence hazard and risk. Central to this endeavour is the Adverse Outcome Pathway (AOP) framework, which organises mechanistic knowledge into a sequence of causally linked events, from the initial molecular perturbation to observable adverse outcomes. By aligning experimental data—ranging from in vitro assays to in vivo observations—within this structured format, researchers can identify critical biological processes, prioritise testing strategies and support regulatory decision making. The integration of omics technologies, systems biology and computational modelling has accelerated the development of predictive tools that can reduce reliance on animal testing, inform safer-by-design approaches and address the growing diversity of nanomaterials in commerce. Globally, these methodologies underpin efforts to safeguard human health and the environment while fostering innovation in nanotechnology.

Research from Nature Portfolio

Recent studies have characterised a conserved transcriptomic signature across multiple species and nanoparticle types, revealing deregulation of immune pathways and stress-related transcription factors as universal hallmarks of nanomaterial exposure. This meta-analysis supports the identification of common molecular initiating events and informs the construction of cross-species AOPs. Parallel work has introduced a multi-omics predictive framework that couples phenotypic toxicity assays with gene-expression markers and material intrinsic properties to group nanomaterials by hazard potential. This approach delivers improved accuracy over physicochemical descriptors alone and yields mRNA-based biomarkers that are robustly validated in independent models. Foundational efforts have also produced network-based computational tools that map nanomaterial-driven perturbations onto networks of genes, proteins and diseases, enabling rapid read-across and hypothesis generation for novel materials.

Nanotoxicology and Adverse Outcome Pathway Modeling publication trend

The graph below shows the total number of articles in nanotoxicology and adverse outcome pathway modeling across all publications each year (not limited to Nature Index journals).

Technical terms

Engineered Nanomaterials (ENMs): Synthetic materials with at least one dimension in the nanoscale, exhibiting unique physicochemical properties.
Adverse Outcome Pathway (AOP): A structured sequence of events from a molecular initiating event through intermediate key events to an adverse biological outcome.
Molecular Initiating Event (MIE): The initial interaction between a nanomaterial and a biomolecule or cell component that triggers a toxic response.
Key Event (KE): A measurable biological change that occurs sequentially after the MIE and contributes to the progression towards the adverse outcome.
Toxicogenomics: The study of genome-wide gene expression changes in response to toxicant exposure to elucidate mechanisms of action.
Network Toxicology: An approach that integrates systems biology and network modelling to map interactions between nanomaterials, molecular pathways and adverse outcomes.

References

1. An ancestral molecular response to nanomaterial particulates. Nature Nanotechnology (2023).
2. Biomarkers of nanomaterials hazard from multi-layer data. Nature Communications (2022).
3. INSIdE NANO: a systems biology framework to contextualize the mechanism-of-action of engineered nanomaterials. Scientific Reports (2019).
4. A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes. Advanced Science (2024).
5. Nanosafety: a Perspective on Nano‐Bio Interactions. Small (2024).
6. Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale. Particle and Fibre Toxicology (2020).