Adverse health effects can be caused by inhaled particles. Particles with an aerodynamic diameter smaller than approximately 4 µm can reach the alveoli, where alveolar macrophages represent the central defence system responsible for particle uptake and clearance. These inhaled particles can induce persistent pulmonary inflammation when macrophage-mediated clearance mechanisms are overwhelmed.
Distinguishing particles that trigger biological activity through intrinsic toxicity from those acting primarily via particle overload represents a central challenge in inhalation toxicology and regulatory safety assessment. Mechanistically anchored new approach methodologies (NAMs) that capture key macrophage responses may therefore provide valuable tools for particle hazard identification while reducing reliance on animal testing.
MACRAMÉ experts have published their recent findings on the alveolar macrophage assay (AMA). This assay was developed as an in vitro method to distinguish particles with intrinsic toxicity from particles that primarily act through macrophage overload. Wiemann et al. (2016) established this assay using rat alveolar macrophages. However, broader application of the method requires evidence that the assay can be reliably produce reproducible results in different laboratories. In the present study, an interlaboratory ring-study was conducted to evaluate the transferability and reproducibility of the AMA.
Twelve different particle-types were tested in three independent laboratories. Across laboratories, comparable dose-response patterns were observed for most endpoints, and seven of the twelve particles were consistently classified as either biologically active or passive according to the established data interpretation procedure. Taken together, the results demonstrate that the AMA can be successfully transferred across laboratories. These findings represent an important step toward the validation of the AMA.
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Thá E, Vennemann A, Marani V, Gräb O, Verlohner A, Ma-Hock L, Spyridonov IM, Weber P, Chary A, Serchi T, Landsiedel R and Wiemann M (2026) Readiness of the in vitro alveolar macrophage assay: an interlaboratory comparison using 12 blinded particles. Front. Toxicol. 8:1844090. doi: 10.3389/ftox.2026.1844090
