Technical report 122

Impact of biosolubility on clearance of deposited particular matter

Several defence mechanisms, located in all three main regions of the respiratory tract (nasopharyngeal, tracheobronchial and alveolar) exist to prevent and clear the mucosal surfaces from contaminant deposition. Classical clearance mechanisms of deposited particles are following two basic pathways, physical translocation of particles and chemical dissolution processes. When inhaled particles are deposited, soluble particles (e.g. NaCl salt) will dissolve in mucus or lung-lining fluid, get access into blood stream, distributed in the body and finally excreted in urine and faeces depending on its physical chemical properties (e.g. molecular weight). In the airway, deposited particles which do not readily dissolve, will be cleared rapidly by mucociliary transport moving particles from the nasal passage and tracheobronchiolar region to the oropharynx, where they are swallowed and are excreted in faeces and, if systemically available, in the urine. Excretion of systemically available substance via bile into faeces may be another possible route, which however cannot be differentiated from those swallowed. In the respiratory unciliated airways and alveoli, particles will get phagocytised within hours by alveolar macrophages (AM) under normal conditions. AM-derived transport is slower than the mucociliary escalator. Phagocytised particles can either move toward the ciliated airways or to lymphatic vessels and the pulmonary lymph nodes. Many studies have shown that excessive dust burdens progressively reduce AM-mediated clearance until it is completely inhibited, a phenomenon known and described earlier in this report as overload (Ferin 1972; Ferin and Feldstein 1978; Lee et al, 1985). Reduced clearance rate are supposed to be related to the loss of macrophage mobility (Morrow 1988). Thus, the potential for particles to dissolve can effectively influence their persistence in the non-ciliated airway and alveoli; and act as a critical control on their biological response. If the solubility and dissolution rate are sufficiently high, a high lung burden leading to overload cannot be built up. In this case, the toxicity will be triggered by dissolved chemical, an “overload”-mediated toxicity as proposed by Morrow (1988) is not applicable for this type of material.

In the sense of being able to build up particle overload, poorly soluble particles are inhaled particles that are removed mainly by AM-mediated clearance, not by dissolution. Whether biosolubility contributes significantly to lung clearance depends strongly on exposure concentration and duration.