Determination of a cytotoxicity threshold for α-Fe2O3 nanoparticles based on an in vitro-in vivo dosimetry model in alveolar epithelial cells.

This study aimed to extrapolate a cytotoxicity threshold in air using a combined in vitro-in vivo dosimetry model to assess the toxicity of α-Fe2O3 nanoparticles (NPs), innovatively applying this approach to NPs risk assessment. Cultured A549 cells treated with α-Fe2O3 NPs in various concentrations over 24-h and 72-h. Cell survival and mitochondrial membrane permeability were assessed using the MTT and MMP assay, respectively. The dose-response results served for estimating the Benchmark Dose (BMD) and BMDL using the EPA BMD software. BMDLs were extrapolated into equivalent air concentrations using the Combined Dosimetry model (CoDo). A significant loss in cell survival and a rise of mitochondrial membrane permeability, compared to the control group (P-value < 0.05), were observed after 24-h and 72-h, respectively. A time- and concentration-dependent pattern was observed in the toxicity of the A549 cell line. Extrapolated from a BMDL of 1.9 μg/mL, a 0.22 mg/m³ air concentration was found to correspond to the in vitro dose. The predicted cytotoxicity threshold falls below the current occupational exposure limits (OELs) for micro-scale particles. Although further in vivo and epidemiological studies are required to validate its relevance for occupational exposure settings, this modeling approach offers a valuable framework for preliminary risk assessment.