Abstract
We have reported previously that grinding crystalline silica generates radicals on its cleavage planes and that this fresh dust is more cytotoxic in vitro than aged silica. The objective of the present study was to determine if freshly fractured silica was also more toxic and inflammatory in vivo than aged silica of the same composition and particle size. Fresh α-quartz was generated using a jet mill, while aged dust was milled and then stored for 2 months before use. Analysis of surface radicals by electron spin resonance spectroscopy verified the enhanced surface activity of this fresh silica compared with aged dust. Male Fischer 344 rats were exposed to fresh or aged α-quartz by inhalation (20 mg/m3, 5 hours per day, 5 days per week for 2 weeks) and pulmonary responses were determined 1 to 3 days after exposure. Exposure to aged silica resulted in an increase in total cells, red blood cells, lymphocytes, and granulocytes harvested by bronchoalveolar lavage, and in elevated acellular lavage protein and phospholipid levels. Furthermore, inhalation of aged silica activated alveolar macrophages (measured as zymosan-stimulated chemiluminescence) and resulted in induction of nitric oxide synthase in these cells (determined as L-NAME inhibitable chemiluminescence). In comparison, inhalation of freshly cleaved silica resulted in dramatically greater increases in all these parameters than did aged silica. Histopathologic inflammation, while mild, followed a similar pattern. In conclusion, methods have been successfully developed to expose rats to fresh or aged α-quartz. The results indicate that inhalation of fresh silica causes greater toxic and inflammatory pulmonary reactions than aged silica. These results may be relevant to occupational settings such as sandblasting, rock drilling, and milling, where workers are exposed to freshly fractured silica.
