4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms

The deposition of airborne fibrous and non-fibrous particles is defined as the active loss of these particles from the air during respiration, as a result of inelastic encounter of the airborne particles with the respiratory epithelium. Clearance from the site of deposition pertains to the removal of these deposited particles by various processes over time, whereas retention is the temporal persistence of particles within the respiratory system (Morrow, 1984). Thus, the amount retained (R) is defined by the amount deposited (D) minus the amount cleared (C) (R = D – C). The deposition of inhaled fibres in the respiratory tract is a function of their physical characteristics (size, shape and density) and of the anatomical and physiological parameters of the upper and lower airways. Chemical composition has no role in deposition of airborne fibres in the respiratory tract, and, therefore, there is no need to differentiate between fibre types when discussing deposition phenomena. The clearance of deposited fibres from the respiratory tract, however, is dependent on both physical and chemical characteristics of fibres, and therefore the clearance and resulting retention behaviour within the respiratory system can vary widely between different fibre types; the different fibres deposited in the lung are subject to the same clearance processes, which together determine the biopersistence of the fibres. Thus, since a general understanding of deposition, retention and clearance is necessary to appreciate the importance of biopersistence, these topics are discussed briefly below for all fibres together rather than considering specific categories of vitreous fibres separately. The main processes leading to the deposition of inhaled fibres operate throughout the respiratory tract, whereas the mechanisms that clear deposited fibres from different regions of the respiratory system vary considerably and, therefore, contribute to a different degree to the retained fibre burden at sensitive sites in the lung. When discussing deposition and retention it is, therefore, convenient to divide the respiratory system into three compartments as follows: the extrathoracic region (ET, consisting of anterior and posterior nose, larynx, pharynx and mouth); the tracheobronchial region (TB, consisting of trachea, bronchi and bronchioles down to the terminal bronchioles) and the alveolar–interstitial region (AI, including respiratory bronchioles, alveolar ducts and sacs with alveoli and pulmonary interstitium). A somewhat more detailed classification in which the respiratory system was divided into four compartments was