Secondary target organs exhibit differential ability to clear cadmium after cadmium oxide nanoparticle inhalation

Inhaled cadmium oxide nanoparticles (CdONPs) represent an underrecognized environmental and occupational hazard because of their potential for systemic bioaccumulation and organ-specific toxicity. In this study, mice were exposed to subchronic inhalation of CdONPs, and cadmium distribution, clearance, and tissue responses were assessed over a 21-day recovery period using atomic absorption spectrometry, laser ablation inductively coupled plasma mass spectrometry, histopathology, and gene expression analysis. Cadmium accumulated predominantly in the lungs, where clearance was slow and accompanied by persistent inflammation and foam cell formation. The intestines exhibited efficient cadmium reduction, likely due to high epithelial turnover, while the liver showed minimal accumulation and no overt damage. By contrast, the kidneys retained cadmium primarily in the cortex, with partial clearance and ultrastructural changes, including mitochondrial disorganization and lipid accumulation. Bone tissues demonstrated differential retention: jaw bones effectively cleared cadmium, whereas femurs showed sustained or increased levels, suggesting redistribution from other organs. Gene expression analysis revealed moderate but consistent upregulation of Abca1, Apoe, and Ptch1 in the kidneys of clearance groups, indicating adaptations in lipid metabolism and membrane transport. These findings highlight organ-specific clearance kinetics and molecular responses to inhaled CdONPs, underscoring the need for tissue-targeted risk assessment frameworks in nanoparticle toxicology.