Dynamic biodistribution of inhaled silica particles to extrapulmonary sites: Early and late translocation mechanisms with implication for particle biomonitoring.

An innovative method based on inductively coupled plasma mass spectrometry (ICP-MS) was developed to quantify the time-dependent systemic redistribution pattern of pulmonary-deposited crystalline silica particles by measuring silicon (Si) levels in the lungs, distal organs, and biological fluids. The method was applied in a murine model and validated in blood and urine samples from two occupationally exposed cohorts (miners and porcelain industry workers). In mice, 30 % of silica particles deposited in the lungs via oropharyngeal administration accumulated in extrapulmonary sites in less than 4 months. An early translocation (within 3 days) resulted in silica distribution to liver and kidneys (13 %), followed by a delayed migration (up to 60 days) in mediastinal lymph nodes (12 %), spleen (1.7 %), and abdominal skin (1.7 %). The long-term increase of Si in urine suggested silica renal clearance. Our data also indicated that the toxic potential of particles is a key determinant of extrapulmonary redistribution. The interest of Si as biomarker of exposure has been confirmed in workers exposed to crystalline silica dust. In these individuals, elevated Si levels in blood and urine paralleled silica exposure. Our findings quantify the dynamics of silica biodistribution in extrapulmonary organs, offering new insights on the biomonitoring of silica exposure in different scenarios.