A new peer-reviewed study reports that methyl methacrylate (MMA), a widely used industrial chemical, does not show evidence of respiratory sensitisation when assessed using a complex human-relevant in vitro lung model.
The study, titled “A novel in vitro alveolar model (ALIsens®) for hazard assessment of methyl methacrylate: No evidence for respiratory sensitisation potential”, demonstrates the regulatory and scientific value of ALIsens®, a patented 3D in vitro alveolar model.
It was conducted by invitrolize in collaboration with BASF and Evonik.
Methyl methacrylate (MMA) is extensively used in the production of polymers, resins, medical devices, coatings, and dental materials.
Despite its long history of use, MMA has been associated with respiratory effects such as irritation, raising questions about its potential to cause respiratory sensitisation.
Until now, the absence of models for the reliable identification of respiratory sensitisers made it difficult to distinguish non-sensitising chemicals from true respiratory sensitisers, creating uncertainty for industries and regulators.
The aim of the project was to answer the question if MMA has the intrinsic property to induce Respiratory Sensitisation. The proposal on classification and labelling is based on 4 unreliable positive human SIC tests.
In this study, researchers used the ALIsens® model to specifically address this gap. ALIsens® is a human cell-based, three-dimensional in vitro model that reconstructs the alveolar‑capillary barrier of the lung. It integrates epithelial cells, endothelial cells, and immune relevant cell types cultured at the air–liquid interface, enabling apical exposure via surface application in a human-relevant co-culture system.
In this study the model was exposed to MMA under controlled and biologically relevant conditions and a panel of markers associated with key events (KEs 2 and 3) of the respiratory sensitisation Adverse Outcome Pathway (AOP #39), was evaluated.
These included immune cell activation markers, notably thymic stromal lymphopoietin receptor (TSLPr) upregulation on the surface of dendritic-like THP-1 cells, and cytokine and chemokine release. The responses observed following MMA exposure were compared with a known respiratory sensitiser, skin sensitiser, and non-sensitising control.
The results clearly showed that methyl methacrylate did not trigger the characteristic molecular and cellular signatures of respiratory sensitisation in the ALIsens® model.
While some transient stress or irritation related responses were observed at higher exposure levels, the data clearly differentiated these effects from immune mediated sensitisation. In the study the highest technically achievable surface doses were used, as cytotoxicity was not observed in the complete model at lower concentrations.
MMA induced a reduction of mitochondrial activity in the endothelial cells present in the system on the basolateral side of the model. This supports the conclusion that MMA should not be classified as a respiratory sensitiser.
Importantly, the study demonstrates that ALIsens® can distinguish between respiratory sensitisation and non-sensitisation – a distinction that is critical for regulatory hazard assessment, chemical classification, and Safe-and-Sustainable-by-Design (SSbD) strategies. The model’s use of immortalized human cell lines ensures reproducibility and supports regulatory relevance; further work would be needed towards formal validation or OECD acceptance, ALIsens® model being one of the most advanced test systems in this process.
These findings provide robust, human relevant evidence to support risk assessment and regulatory decision making for methyl methacrylate, while also showcasing the broader applicability of ALIsens® for evaluating inhalable chemicals.
As regulatory expectations evolve and animal testing continues to be phased out, this study highlights how advanced in vitro models can deliver clear, mechanistic, and decision ready data for respiratory safety assessment.
The full scientific paper can be found here.
