Chronic Inflammation and Tumor Formation in Rats After Intratracheal Instillation of High Doses of Coal Dusts, Titanium Dioxides, and Quartz

Abstract

Coal mine dust’s possible carcinogenicity has recently drawn attention because of the IARC review of quartz, some new epidemiological data in German coal miners, and findings on other poorly soluble, nontoxic dusts in the rat. The aim of this study was to investigate persistent inflammation and tumor response in the rat after intratracheal instillation of two coal dust samples and other dust preparations. Female Wistar rats (190 g) were instilled with ground lean coal (60 mg) coal mine dust (60 mg), DQI2 quartz (5 mg), and fine (60 mg) and ultrafine (30 mg) TiO₂. After 129 wk rats were killed, tumors detected by microscopy, and inflammation by light microscopy after specific antibody staining for macrophages and granulocytes. Increased alveolar macrophages (AM) and interstitial granulocytes were still present in dust-treated animals. Both AM and granulocytes per surface area were related to tumor incidence when all materials were plotted in one graph, and can be interpreted as effects of overload. Differences in tumor formation between fine and ultrafine TiO₂, despite similar inflammatory response, are probably caused by a direct effect of ultrafine TiO₂ after interstitialization. It is concluded that coal dust is another poorly soluble, nontoxic dust, which at high enough dose rate causes overload, inflammation, and tumor response in the rat.