The current carcinogenicity study with female rats focused on the toxicity and carcinogenicity of intratracheally instilled fine and ultrafine granular dusts. The positive control, crystalline
silica, elicited the greatest magnitude and progression of pulmonary inflammatory reactions,
fibrosis and the highest incidence of primary lung
tumors (39.6%). Addition of poly-2-vinylpyridine-N-oxide decreased inflammatory responses,
fibrosis, and the incidence of pulmonary
tumors induced by crystalline
quartz to 21.4%. After repeated instillation of soluble, ultrafine amorphous
silica (15 mg) a statistically significant
tumor response (9.4%) was observed, although, the inflammatory response in the lung was not as persistently severe as in rats treated with
carbon black. Instillation of ultrafine
carbon black (5 mg) caused a lung
tumor incidence of 15%. In contrast to a preceding study using a dose of 66 mg
coal dust, lung
tumors were not detected after exposure to the same
coal dust at a dose of 10 mg in this study. Pulmonary inflammatory responses to
coal dust were very low indicating a mechanistic threshold for the development of lung
tumors connected with particle related chronic
inflammation. The animals treated with ultrafine
carbon black and ultrafine amorphous
silica showed significantly more severe lesions in non-cancerous endpoints when compared to animals treated with fine
coal dust. Furthermore,
carbon black treated rats showed more severe non-cancerous lung lesions than amorphous
silica treated rats. Our data show a relationship between
tumor frequencies and increasing scores when using a qualitative scoring system for specific non-cancerous endpoints such as
inflammation,
fibrosis, epithelial
hyperplasia, and squamous
metaplasia.