Besides physical translocation of deposited particles, chemical dissolution is one of the basic clearance principles of the respiratory tract. In this respect (bio)solubility is of importance, because chemical dissolution is especially targeted at biosoluble particles which are dissolved in intracellular or extracellular fluids and may then be cleared into blood or lymphatic circulation. Thus, chemical clearance of biosoluble particles can happen within all three major regions of the respiratory tract, i.e. the nasopharyngeal, tracheobronchial and/or alveolar region. In contrast, pathways for physical translocation of inhaled particles of low (bio)solubility are not only limited and arranged differently in these three regions, but some of them show also significant particle-size dependent differences. As the most prevailing clearance mechanism for solid particles in the alveolar region is mediated by alveolar macrophages, differences in the biosolubility of particles can considered to be a major determinant with regard to the establishment of `particle lung overload’ conditions.
Summarising all available facts, biosolubility may differ significantly from solubility determined in water. It is influenced by different physical-chemical properties of the materials and is also influenced by the biological system. In vivo, biosolubility may therefore contribute significantly to the clearance rate of particular matter deposited in the deep lung and influence directly the retention rate of particular matter, thus becoming an important driver at which doses lung overload develops.