Relationship of pulmonary toxicity and carcinogenicity of fine and ultrafine granular dusts in a rat bioassay

Abstract

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.

Keywords::

• Rats
• histopathology
• pulmonary neoplasms
• inflammation
• granular dusts

Acknowledgements

The authors thank Prof. F.Pott for initiating and attending this research project, Dr. Rupert Kellner for the statistic analysis of the histopathological data and Dr. Andreas Kolling for creating the histograms.

Declaration of interest

The material for histopathological investigation was generated in a study supported by Federal Environmental Agency and Federal Environment Ministry, Germany, grant no. 29861273. The authors report no conflicts of interest.