Pja. Borm et al., Chronic inflammation and tumor formation in rats after intratracheal instillation of high doses of coal dusts, titanium dioxides, and quartz, INHAL TOXIC, 12, 2000, pp. 225-231
Coalmine dust's possible carcinogenicity has recently drawn attention becau
se of the IARC review of quartz, some new epidemiological data in German co
al 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 samp
les and other dust preparations. Female Wistar rats (190 g) were instilled
with ground lean coal (60 mg), coal mine dust (60 mg), DQ12 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 s
pecific antibody staining for macrophages and granulocytes. Increased alveo
lar macrophages (AM) and interstitial granulocytes were still present in du
st-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 probab
ly caused by a direct effect of ultrafine TiO2 after interstitialization. i
t is concluded that coal dust is another poorly soluble, nontoxic dust, whi
ch at high enough dose rate causes overload inflammation, and tumor respons
e in the rat.