In vitro assessment of biopersistence using mammalian cell systems

Abstract

Biopersistence of fibers in the respiratory airways is a concept including both the physical durability of the fibers and their chemical stability. Physical durability results from several events of diverse origins: fiber epuration by the lung clearance mechanisms, internalization by scavenger cells and fiber splitting. Fibers residing in the lung milieu will be attacked and modified chemically, structurally, and physically (size and shape). Fiber toxicity, which is very likely to be dependent on physical fiber characteristics, will also be dependent on the duration of the fiber's stay in the tissue. Biopersistence, therefore, will be a key issue in determining fiber toxicity. So far, few in vitro systems have been used to study parameters involved in biopersistence. However, examples exist of investigations of fiber phagocytosis by mammalian cells in culture, either by macrophages, or epithelial or mesothelial cells, and studies have also been reported of the fate of internalized fibers in relation to fiber dimensions and chemical stability, especially within macrophages and mesothelial cells. The methods will be presented and discussed to determine to what extent the development of in vitro biophysical models could help in determining those parameters, known or thought to be relevant to fiber persistence.