Nanomaterial Toxicity Assessments in Pulmonary Models

Summary

The rapid expansion of engineered nanomaterials across industry and consumer products has catalysed efforts to understand their potential pulmonary hazards. Toxicity assessments now encompass a spectrum of models ranging from traditional rodent inhalation studies to advanced in vitro systems that more closely recapitulate human lung structure and function. Two‐dimensional monolayer cultures of alveolar epithelial cells have evolved into co-culture and three-dimensional constructs incorporating macrophages, fibroblasts and endothelial cells. Air–liquid interface exposure platforms permit direct aerosol delivery under physiologically relevant conditions, while computational tools estimate realistic lung doses. Key endpoints include cytotoxicity, oxidative stress, inflammatory mediator release and genotoxicity. Linking in vitro findings to in vivo outcomes through quantitative extrapolation frameworks supports risk assessment and the safe‐by‐design paradigm. Such integrative approaches inform regulatory decisions, guide occupational exposure limits and underpin the development of safer nanomaterials with minimal respiratory impact.

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Nanomaterial Toxicity Assessments in Pulmonary Models publication trend

The graph below shows the total number of articles in nanomaterial toxicity assessments in pulmonary models across all publications each year (not limited to Nature Index journals).

Technical terms

Air–liquid interface (ALI) exposure: A cell culture method in which epithelial cells are nourished basally by medium while their apical surface is directly exposed to aerosols, better mimicking respiratory conditions.

New approach methodologies (NAMs): Alternative non-animal testing strategies combining in vitro assays, organ-on-chip devices and computational models to assess hazard and reduce reliance on in vivo studies.

Multiple‐path particle dosimetry (MPPD) model: A computational tool used to predict deposition and distribution of inhaled particles in different regions of the respiratory tract.

In vitro–in vivo extrapolation (IVIVE): A quantitative framework that aligns laboratory‐derived dose–response data with organismal outcomes to support risk assessment.

Co-culture model: An in vitro system in which two or more cell types are grown together to reproduce key cellular interactions found in native tissues.

References

  1. An integrated new approach methodology for inhalation risk assessment of safe and sustainable by design nanomaterials. Environment International (2024).
  2. Establishing relationships between particle-induced in vitro and in vivo inflammation endpoints to better extrapolate between in vitro markers and in vivo fibrosis. Particle and Fibre Toxicology (2023).
  3. Modular air–liquid interface aerosol exposure system (MALIES) to study toxicity of nanoparticle aerosols in 3D-cultured A549 cells in vitro. Archives of Toxicology (2024).
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