Theoretical approach to the hit probability of lung-cancer-sensitive epithelial cells by mineral fibers with various aspect ratios

Background: Inhalation of fibers may lead to the damage and, as a further consequence, to the malignant transformation of specific (most of all non-ciliated) cells of the bronchial and bronchiolar airway epithelium. In order to accurately estimate the cancer risk induced by inhaled fibers, hit probabilities of non-ciliated (secretory) cells by mineral fibers (asbestos and chrysotile) were computed. Methods: Besides the use of a stochastic lung geometry and a particle transport/depositionmodel being based upon the random-walk algorithm, histological data of cell distributions in the human lungs were applied for the theoretical calculations. Diameters of computer-generated fibers ranged from 0.1 mu m to 10 mu m, whilst two values (3 and 100) were selected for the aspect ratios (ratios of fiber length to fiber diameter), thereby simulating the behavior of short and very long fibrous particles. Results: According to the modeling results, the highest regional hit probabilities (up to 10%) are available for fibers with a diameter of 1.0 mu m, whereby cells of the bronchiolar compartment represent a preferential target of these particles. For fibers with a diameter of 0.1 mu m, bronchiolar hit probabilities reach 2-3%, whereas fibers with a diameter of 10 mu m penetrate to the peripheral lung parts with only low amounts (<0.1%). A change of the inhalation conditions from sitting to light-work breathing enhances the extrathoracic and bronchial filtering of large particles (diameter >= 1 mu m), whilst penetration of small particles towards distal lung airways is subject to a reinforcement. Further refinement of hit probabilities by considering single airway generations results in the circumstance that fibers with diameters <= 1.0 mu m preferably collide with cancer-sensitive cells of airway generations 12-15. In contrast, fibers with a diameter of 10 mu m mainly represent a hazard for cancer-sensitive cells being located in the uppermost airways. A change of breathing conditions both supports the effect of short fibers and enhances the filtering of long ones. Conclusion: Based upon the results of this contribution it can be concluded that highest cancer risk is generated by the inhalation of mineral fibers with diameters <1.0 mu m, whereby fiber length has to be classified as a parameter with lower importance.