The neutralization of silica toxicity in vitro.

Although the capacity of aluminium to prevent experimental silicosis in animals appears to be well established (Dworski, 1955), there is no adequate evidence at present that it can influence the course of silicosis in man. Moreover, it must be administered to man by inhalation and may not be entirely innocuous itself. Recently Marks, Mason, and Nagelschmidt (1956) have described a method for evaluating antagonists to silica in tissue culture. This technique is suitable for screening large numbers of drugs, and the present paper records the encouraging results. Organic bases are possible alternatives to aluminium, and attention was directed at first to those bases known to combine with silicic acid, e.g., cytochrome c and methylene blue (James and Marks, 1956). The observation that this basic protein and basic dye precipitated polydisperse (polymerized) silicic acid recalled the well-known precipitation of the polyacidic substance heparin by protamine and toluidine blue. Several compounds known to react with heparin were therefore examined to see if they would neutralize silica toxicity. A number of these have been studied for their activity as histamine liberators (MacIntosh and Paton, 1949). A recently discovered and unusually active substance of this type, compound 48/80, proved to be of great interest. It is prepared by the condensation of p-methoxy-phenylethyl-methylamine with formaldehyde (Paton, 1951), and, existing as a mixture of low polymers, has the following general formula:NHCH3 NHCH3 I CH2 CH2