Europe-wide test of material assessment method

Adolphe Merkle Institute researchers from the BioNanomaterials have coordinated a Europe-wide consortium in testing the accuracy of a system for hazard assessment of aerosolized materials, an important step in developing standardized assays for lung cell models.

Air-liquid interface (ALI) lung cell models are used for assessing respiratory hazards. These models involve culturing cells on permeable inserts, and exposing them to aerosolized materials. How accurate the dosage of these materials is across multiple laboratories is not entirely clear, although extremely important since results should be reproducible and comparable.

Inter-laboratory studies are essential for implementing ALI cultures used in vitro hazard assessment of materials. Furthermore, the method adopted should be both robust and reproducible to ensure regulatory acceptance. Such a comparison study should include a standardized operating procedure (SOP) for a specific method, which is necessary to ensure globally harmonized testing approaches, and should be in line with guidance from, e.g., the Organization for Economic Co-operation and Development (OECD). These guidelines were developed with the aim of reducing the uncertainties in cell and tissue-based in vitro method-derived predictions.

The AMI BioNanomaterials group collaborated with a total of seven European partners, including from the PATROLS (Physiologically Anchored Tools for Realistic nanOmateriaL hazard aSsessment) consortium, and coordinated an approach to investigate the accuracy of a commercially available aerosol-cell exposure system to deliver a controlled dose of aerosolized materials to lung cells at ALI. The researchers developed an SOP to deliver aerosolized materials with the VITROCELL® Cloud12 system. The amount of material deposited on the inserts was measured using a quartz crystal microbalance (QCM) integrated into the exposure system for the particles. The researchers also examined the shape and agglomeration state of the deposited particles using transmission electron microscopy.

The inter-laboratory comparison focused on materials, with the goal of determining if the QCM could be a reliable measurement system. Differences in aerosol deposition at the different laboratories were characterized using a deposition factor, which helps predict the material dose deposited on the inserts based on the concentration of materials in the aerosolized suspension. The SOP was continuously adapted and optimized.

The system accurately measured the deposited material dose on the inserts. For the materials, a linear relationship was observed between the concentration of materials in the aerosolized suspension and the QCM-determined dose delivered to the inserts. The results suggest that the VITROCELL® Cloud 12 system is a reliable tool for dosimetry. According to the researchers, this advancement is significant for the future implementation of lung cell cultures at ALI in regulatory-approved assessments of aerosolized materials' hazards.

Reference: Bannuscher, A.; Schmid, O.; Drasler, B.; Rohrbasser, A.; Braakhuis, H. M.; Meldrum, K.; Zwart, E. P.; Gremmer, E. R.; Birk, B.; Rissel, M.; Landsiedel, R.; Moschini, E.; Evans, S. J.; Kumar, P.; Orak, S.; Doryab, A.; Erdem, J. S.; Serchi, T.; Vandebriel, R. J.; Cassee, F. R.; Doak, S. H.; Petri-Fink, A.; Zienolddiny, S.; Clift, M. J. D.; Rothen-Rutishauser, B. An Inter-Laboratory Effort to Harmonize the Cell-Delivered in Vitro Dose of Aerosolized Materials. NanoImpact 2022, 28, 100439.