Freshly Fractured Silica Exerts Greater Toxicity To Lung Macrophages Than Aged Dust: Organosilane (Prosil 28) Coating Markedly Reduces Dust Toxicity To Cells

Previously we reported crushing or grinding crystalline silica results in silica-based free radicals on the particulate surface which can generate hydroxyl radicals in aqueous solution (1). Now we find that freshly ground silica is more cytotoxic to and a more potent activator of alveolar macrophages than similarly sized aged silica. Since the United States Department of Labor estimates that over 1.25 million American workers may be exposed to freshly ground crystalline silica arid nearly 60,000 may be at risk of developing some degree of silica-based occupational lung disease, then this is hardly a trivial problem. Occupations of concern include workers who come in contact with silica including miners of soft and hard minerals, stone quarry workers, glass workers and even millers who stone grind flour. Acute silicosis is manifested by inflammation, alveolar lipo-proteinosis, and the rapid development of respiratory disability that depending on the dose of silica can produce chronic silicosis which takes 20 - 40 years to develop. It is demonstrated by the appearance of concentric hyalinized nodular lesions and progressive development of dyspnea(3). Certainly the free radicals produced on the surface of freshly ground crystalline silica play a most important role in producing the acute and chronic symptoms of silicosis. When respirable-size freshly- ground silica (0.1 -- 5 microns in diameter) enters the deep alveolar spaces in the lung and contacts an aqueous environment, hydroxyl radical are generated and cellular damage is bound to occur. We have found that freshly ground silica can cause lipid peroxidation and lysis of erythrocytes(1). The objective of this investigation was to further elucidate the enhanced toxicity of freshly ground versus aged silica. It can be deduced from the data that not only is freshly ground silica more cytotoxic to alveolar macrophages but it is a more potent stimulant of these phagocytes. However the mere characterization of toxicity is not entirely helpful if there is not a useful means to detoxify the cause of the damage. We have identified an aqueously soluble substance that can be used in high dilution to detoxify the SiO(•) and Si(•) type of free radicals. This is the organosilane known as Prosil 28 (R). We have found that coating of the freshly ground silica can effectively reduce its toxicity. The importance of this observation is that such a coating could be used with water cooled drills. This may partially detoxify silica at the point of generation of the free radical, i.e., the generation of the fresh silica dust itself. Such a coating could be used in great dilution 1:103 or 1:104. The coating would be long lasting, inexpensive and should be non-toxic because of the great dilution.