Interlaboratory ring study demonstrates reproducible hazard identification in twelve blinded particles, supporting alveolar macrophage assays for animal-free safety testing.
Key Points
Evaluate the interlaboratory transferability, reproducibility, and readiness of the in vitro alveolar macrophage assay as an animal-free alternative for mechanistic particle hazard identification.
Conducted an interlaboratory ring study across three independent laboratories using standardized protocols and predefined acceptance criteria.
Assessed 12 blinded particles across four mechanistic biological endpoints: oxidative stress, lysosomal activation, cytotoxicity, and inflammatory signaling.
Consistently classified 7 of the 12 blinded particles as either biologically active or passive across all three laboratories using the established data interpretation procedure.
Observed comparable dose-response relationships for most endpoints, though variations occurred due to assay sensitivity and partial particle solubility.
Identified fetal bovine serum as a primary contributor to experimental variability across sites, demonstrating the necessity of chemically defined culture media.