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Pulmonary tumor types induced in Wistar rats of the so-called "19-dust study"

: Mohr, U.; Ernst, H.; Roller, M.; Pott, F.


Experimental and Toxicologic Pathology 58 (2006), No.1, pp.13-20
ISSN: 0940-2993
Journal Article
Fraunhofer ITEM ()
coal dust; TiO2; Amorphous SiO2; Al-oxide; Al-silicate; Lungs; Lungs - Tumors; Rats; Particles; Carbon black

The incidences of primary lung tumor types histologically diagnosed in 28 groups of Wistar rats of the so-called "19-dust study" are described, the total study having been already presented by Pott and Roller (Carcinogenicity study with nineteen granular dusts in rats. Eur J Oncol, 2005; 10: 249-81). Each exposed group was repeatedly instilled intratracheally with a suspension of one type and dose of 13 non-mining dusts differing in at least one of the following properties: chemical composition, density, specific surface area, and mean particle size. Eleven of the 13 dusts were classified as respirable granular bio-durable particles without known significant specific toxicity (abbreviation of the nine-word definition: GBP). In 579 (58%) lungs of 1002 rats which survived more than 26 weeks after the first instillation of GBP, at least one primary lung tumor type was observed, and in 306 (31%) at least two types. Three benign tumor types were diagnosed in the 579 tumor-bearing rats: bronchiolo-alveolar adenoma in 46%, cystic keratinizing epithelioma in 53%, and non-keratinizing epithelioma in 2.6% of the rats. Two of three malignant tumor types (bronchiolo-alveolar carcinoma and squamous cell carcinoma) occurred in 46% and 31% of the tumor-bearing rats, respectively, and adenosquamous carcinoma was diagnosed in 0.9%. Numerous lungs with a malignant tumor also showed one or more benign tumor types. In addition, single or multiple metastases from primary tumors of other sites (mainly carcinoma of the uterus) were diagnosed in 14% of the 1002 lungs. The proportionate incidences of the four predominantly diagnosed tumor types were compared with three summarized experimental groups which were exposed either to carbon black (two size classes), to titanium dioxide (two size classes), or to the total of the other nine GBP. A significant difference was not detected. The combination of dust volume with particle size correlated best with the carcinogenic effect, in contrast to dust mass and surface area.